A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Vocalizations play a critical role in mate recognition and mate choice in a number of taxa, especially, but not limited to, orthopterans, frogs, and birds. But receivers can only recognize and prefer sounds that they ...Vocalizations play a critical role in mate recognition and mate choice in a number of taxa, especially, but not limited to, orthopterans, frogs, and birds. But receivers can only recognize and prefer sounds that they can hear. Thus a fundamental question linking neurobiology and sexual selection asks-what is the threshold for detecting acoustic sexual displays? In this study, we use 3 methods to assess such thresholds in tdngara frogs: behavioral responses, auditory brainstem responsesz and multi unit electrophysiological recordi ngs from the midbrain.We show that thresholds are lowest for multiunit recordings (ca. 45 dB SPL), and then for behavioral responses (ca. 61 dB SPL), with auditory brainstem responses exhibiting the highest thresholds (ca. 71 dB SPL). We discuss why these estimates differ and why, as with other studies, it is unlikely that they should be the same. Although all of these studies estimate thresholds they are not measuring the same thresholds;behavioral thresholds are based on signal salienee whereas the 2 neural assays estimate physiological thresholds. All 3 estimates, however, make it clear that to have an appreciation for detection and salienee of acoustic signals we must listen to those signals through the ears of the receivers.展开更多
Advancements in neuroscience research present opportunities and challenges,requiring substantial resources and funding.To address this,we describe here“Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT)”,...Advancements in neuroscience research present opportunities and challenges,requiring substantial resources and funding.To address this,we describe here“Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT)”,an open-source,versatile,and cost-effective apparatus for intertemporal choice testing in rodents.This allows quantification of delay discounting(DD),a cross-species phenomenon observed in decision making which provides valuable insights into higher-order cognitive functioning.In DD,the subjective value of a delayed reward is reduced as a function of the delay for its receipt.Using our apparatus,we implemented an effective intertemporal choice paradigm for the quantification of DD based on an adjusting delayed amount(ADA)algorithm using mango juice as a reward.Our paradigm requires limited training,a few 3D-printed parts and inexpensive electrical components,including a Raspberry Pi control unit.Furthermore,it is compatible with several in vivo procedures and the use of nose pokes instead of levers allows for faster task learning.Besides the main application described here,the apparatus can be further extended to implement other behavioral tests and protocols,including standard operant conditioning.In conclusion,we describe a versatile and cost-effective design based on Raspberry Pi that can support research in animal behavior,decision making and,more specifically,delay discounting.展开更多
The synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) was used to induce innate fear in male GAD67 mice and behavioral changes were correlated with c-fos mRNA levels as marker for neuronal activation...The synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) was used to induce innate fear in male GAD67 mice and behavioral changes were correlated with c-fos mRNA levels as marker for neuronal activation to reveal underlying activated fear circuits. Results show the same amount of increased freezing and decreased rearing and grooming behavior of TMT-exposed GAD67 mice and wild type littermates, and therefore suggest that heterozygous knock-in of GFP in the GAD67 gene that is associated with a fifty percent decreased GAD67 protein level in the brain, has no impact on TMT-induced behavioral effects. Exposure to TMT significantly increased the number of c-fos mRNA positive cells in the main olfactory bulb (MOB), the lateral septum (LS), the bed nucleus of the stria terminalis (BNST), the central amygdala (CeA), the anterior-ventral (MeAav), the anterior-dorsal (MeAad) and the posterior-ventral (MeApv) part of the medial amygdala in GAD67 mice. Thus, to further investigate the role of GABAergic neurons in TMT-induced uncontrollable stress responses GAD67 mice that provide the advantage of prelabeled GABAergic neurons through the GABA neuron specific expression of GFP could be a suitable model organism.展开更多
Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of ca...Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.展开更多
BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different etiologies.The pathomechanisms of MH encompass various conditions.The etiologica...BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different etiologies.The pathomechanisms of MH encompass various conditions.The etiological classification of MH is of particular importance and offers valuable insights to understand MH,and further to develop the effective treatment of MH.Over the recent decades,more MH cases have been reported,revealing newly identified medical and psychiatric causes of MH.Functional imaging studies reveal that MH activates a wide array of brain regions.An up-to-date analysis on MH,especially on MH comorbid psychiatric conditions is warranted.AIM To propose a new classification of MH;to study the age and gender differences of MH in mental disorders;and neuropathology of MH.METHODS Literatures searches were conducted using keywords such as“music hallucination,”“music hallucination and mental illness,”“music hallucination and gender difference,”and“music hallucination and psychiatric disease”in the databases of PubMed,Google Scholar,and Web of Science.MH cases were collected and categorized based on their etiologies.The t-test and ANOVA were employed(P<0.05)to compare the age differences of MH different etiological groups.Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed.RESULTS Among the 357 yielded publications,294 MH cases were collected.The average age of MH cases was 67.9 years,with a predominance of females(66.8%females vs 33.2%males).MH was classified into eight groups based on their etiological mechanisms.Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses.CONCLUSION We carried out a more comprehensive review of MH studies.For the first time according to our knowledge,we demonstrated the psychiatric conditions linked and/or associated with MH from statistical,biological and molecular point of view.展开更多
Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a numb...Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.展开更多
Given the failure to develop disease-modifying therapies for Alzheimer’s disease(AD),strategies aiming at preventing or delaying the onset of the disease are being prioritized.While the debate regarding whether depre...Given the failure to develop disease-modifying therapies for Alzheimer’s disease(AD),strategies aiming at preventing or delaying the onset of the disease are being prioritized.While the debate regarding whether depression is an etiological risk factor or a prodrome of AD rages on,a key determining factor may be the timing of depression onset in older adults.There is increasing evidence that untreated early-onset depression is a risk factor and that late-onset depression may be a catalyst of cognitive decline.Data from animal studies have shown a beneficial impact of selective serotonin reuptake inhibitors on pathophysiological biomarkers of AD including amyloid burden,tau deposits and neurogenesis.In humans,studies focusing on subjects with a prior history of depression also showed a delay in the onset of AD in those treated with most selective serotonin reuptake inhibitors.Paroxetine,which has strong anticholinergic properties,was associated with increased mortality and mixed effects on amyloid and tau deposits in mice,as well as increased odds of developing AD in humans.Although most of the data regarding selective serotonin reuptake inhibitors is promising,findings should be interpreted cautiously because of notable methodological heterogeneity between studies.There is thus a need to conduct large scale randomized controlled trials with long follow up periods to clarify the dose-effect relationship of specific serotonergic antidepressants on AD prevention.展开更多
Abstract Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobi- ological mechanism underlying propofol reward is not fully understood. The purpose of this study was...Abstract Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobi- ological mechanism underlying propofol reward is not fully understood. The purpose of this study was to inves- tigate the role of extracellular signal-regulated kinase （ERK） signal transduction pathways in the nucleus accumbens （NAc） in propofol self-administration. We tested the expression of p-ERK in the NAc following the maintenance of propofol self-administration in rats. We also assessed the effect of administration of SCH23390, an antagonist of the D1 dopamine receptor, on the expression of p-ERK in the NAc in propofol self-administering rats, and examined the effects of intra-NAc injection of U0126, an MEK inhibitor, on propofol reinforcement in rats. The results showed that the expression of p-ERK in the NAc increased significantly in rats maintained on propofol, and pre-treatment with SCH23390 inhibited the propofol self- administration and diminished the expression of p-ERK in the NAc. Moreover, intra-NAc injection of U0126 （4 μg/ side） attenuated the propofol self-administration. The data suggest that ERK signal transduction pathways coupledwith D1 dopamine receptors in the NAc may be involved in the maintenance of propofol self-administration and its rewarding effects.展开更多
A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments....A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments. Roots of the self-medication concept in psychiatry date back at least to the 1980 s. Observations that rates of smokers in schizophrenic patients are multiple times the rates for regular smoking in the general population, as well as those with other disorders, proved particularly tempting for a self-medication explanation. Additional evidence came from experiments with animal models exposed to nicotine and the identification of neurobiological mechanisms suggesting self-medication with smoking is a plausible idea. More recently, results from studies comparing smoking and non-smoking schizophrenic patients have led to the questioning of the self-medication hypothesis. Closer examination of the literature points to the possibility that smoking is less beneficial on schizophrenic symptomology than generally assumed while clearly increasing the risk of cancer and other smoking-related diseases responsible for early mortality. It is a good time to examine the evidence for the self-medication concept as it relates to smoking. Our approach is to focus on data addressing direct or implied predictions of the hypothesis in schizophrenic smokers.展开更多
Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent ...Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.展开更多
Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has dem...Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1(IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sexhormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinasesignaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar signaling cascades. Future research on both neuroprotection and diabetes should include androgens into the interplay of IGF1 and sex hormones.展开更多
Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous system.In recent years,BDNF has received considerable atten...Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous system.In recent years,BDNF has received considerable attention for its importance in the development and maintenance of normal brain function.This is because BDNF plays an important role in crucial functions of the nervous system,such as the survival,differentiation,and maturation of neurons and glial cells as well as the actions of neuroprotection in adverse conditions,such as glutamatergic overstimulation,cerebral ischemia,hypoglycemia,and neurotoxicity(Kowiański et al.,2018).展开更多
Patients with schizophrenia undergo changes in brain plasticity. In the present study, we characterized motor cortical-striatal plasticity in such patients. Compared with the potentiation following high-frequency repe...Patients with schizophrenia undergo changes in brain plasticity. In the present study, we characterized motor cortical-striatal plasticity in such patients. Compared with the potentiation following high-frequency repetitive transcranial magnetic stimulation in the control group, the patients demonstrated impaired plasticity of corticostriatal motor-evoked potentials recorded from hand muscles.Notably, the loss of cortical plasticity was correlated with impaired motor learning in a rotary pursuit task. Moreover,the loss of plasticity was correlated with the symptoms of schizophrenia. The results suggest that the progression of schizophrenia is accompanied by altered cortical plasticity and functioning.展开更多
Alzheimer＇s disease is the most common neurodegenerative disorder and no disease-modifying treatment is currently available.Research has shown that while brain neurogenesis continues in adult life,it declines with ag...Alzheimer＇s disease is the most common neurodegenerative disorder and no disease-modifying treatment is currently available.Research has shown that while brain neurogenesis continues in adult life,it declines with age.Using parabiosis,plasma transfusions and direct administration of neural growth factors,animal studies have demonstrated the positive impact of exposure to young blood products on neurogenesis and synaptic plasticity in an aging brain.The hippocampus and the sub-ventricular zones were identified as the main regions affected.Promising findings have prompted researchers to experiment their effects in subjects with an established neurocognitive disorder,such as Alzheimer＇s disease.They argued that modification of brain vasculature,reactivation of adult neural stem cells,and remodeling of their synaptic activity/plasticity may lead to cognitive enhancement and increased neurogenesis.One pilot human study found that young donor plasma infusion protocols for adults with Alzheimer＇s disease were safe and feasible;however,no statistically significant improvements in cognition were detected.There is a need to conduct additional placebo-controlled human studies in larger samples.Future studies should focus on identifying an “optimal age” at which an intervention in humans may yield significant cognitive enhancement,as well as determining the types of transfusions with the best efficacy and tolerability profiles.展开更多
Acoustic communication in many anuran species can show the effects of both natural and sexual selection. This is reflected in the sexually dimorphic an atomy of the lary nx and ear structures, as well as the allometri...Acoustic communication in many anuran species can show the effects of both natural and sexual selection. This is reflected in the sexually dimorphic an atomy of the lary nx and ear structures, as well as the allometric relationship of these morphological traits to head or body size. In this study, we examined laryngeal and ear structures of cricket frogs Acris crepitans not only as sexually dimorphic characteristics, but also as they differ across populations in environmentally different habitats. We used 2-way ANOVA to determine whether the volumetric or linear measurements of these structures differed by sex and population. Females have significantly larger body, head, and ear sizes, but significantly smaller larynges than males. Furthermore, females as well as males show larger body and head sizes, ears, and larynges in a dryer open habitat. An ANCOVA analysis shows that males, but not females, differ in laryngeal size across populations beyond the allometric changes attributable to head size alone indicating that males have a greater degree of laryngeal population variation. In contrast, our covariate analysis found that in both sexes many of the ear differences are non-sigrdficant once head size is accounted for, suggesting that most of the population-level ear variation is due to allometric effects of body size. We conclude that although both sexes show size differences in the larynx related to selection for larger body size in dry, open habitats, selection on males for larger larynx size related to the production of lower frequency calls in those habitats does not result in correlated changes in the female larynx. The results suggest that in anurans, selection for changes in body and head size affects both sexes equally, male calls and the vocal structures responsible for them can further diversify without concordant changes in females.展开更多
Activation of presynaptic group II metabotropic glutamate receptors（mGluR2/3） inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate（NAAG）, an agonist of endogenous mGluR2/3,in h...Activation of presynaptic group II metabotropic glutamate receptors（mGluR2/3） inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate（NAAG）, an agonist of endogenous mGluR2/3,in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroinseeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1（FR1） schedule for 10 days,then received NAAG（50 or 100μg/10 μL in each nostril）in the absence or presence of LY341495（1 mg/kg, i.p.）, an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin selfadministration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroinpriming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG,via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.展开更多
The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent f...The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.展开更多
Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefor...Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefore, agent(s) capable of inhibiting brain amyloid deposition might delay the occurrence or retard the progress forwards of AD and related neurobehavioral symptoms. Here, we report whether, chronic oral administration of Syzygium cumini (locally known as Jam)-seed extract exerts protection against the progressive cognitive decline in the Aβ1-40-infused AD model rats. After 12 weeks of feeding with S. cumini seed extract (at 300 mg/kg BW), we evaluated the learning-related memory of the rats by 8-arm radial maze task, where we determined two types of memory errors, namely reference memory errors (RMEs) and working memory errors (WMEs). After completion of memory tests, rats were sacrificed and the levels of lipid peroxide (LPO), the Aβ1-40-burden, Aβ1-40-oligomers, proinflammatory TNFα, brain derived neurotrophic factor (BDNF), Tyrosine-kinase B (TrkB), postsynaptic-density protein 95 (PSD-95) and Synapse-associated protein (SNAP-25) were determined in the corticohippocampal tissues of the brain. In addition, in vitro antioxidative effects of S. cumini seed extract were evaluated. The oral administration of S. cumini extract significantly increased the memory-related learning ability of the AD model rats, concomitantly with reductions in the levels of corticohippocampal Aβ1-40-burden and Aβ1-40-oligomers. Furthermore, the extract suppressed the levels of TNFα and LPO in the corticohippocampal tissues of the AD rats and also the later in the plasma, suggesting an anti-oxidative and anti-inflammatory activities of the S. cumini extract in the brains of AD model rats. S. cumini extract also increased the levels of brain cognition and memory-related proteins, including BDNF, TrKB, PSD-95 and SNAP-25. We thus suggest that S. cumini-seed extract could be used in neurobehavioral deficits and associated pathogenesis of Alzheimer’s disease.展开更多
Previous evidence suggests that emotion dysregulation may have different biological correlates between adults and children/adolescents. Although the role of genetic factors has been extensively studied in adult-onset ...Previous evidence suggests that emotion dysregulation may have different biological correlates between adults and children/adolescents. Although the role of genetic factors has been extensively studied in adult-onset emotion dysregulation, the genetic basis for pediatriconset emotion dysregulation remains elusive. The current review article presents a summary of previous studies that have suggested a few genetic variants associated with pediatric emotion dysregulation. Among these candidate loci, many prior studies have been focused on serotonin transporter promoter gene polymorphism 5-HTTLPR. Certain alleles of the 5-HTTLPR gene polymorphism have been found to be associated with traits associated with emotion dysregulation, such as aggression, affect reactivity, and insecure attachment. Additionally, genetic variants involving dopamine and neurophysiological biomarkers like the COMT Val158Met(rs460) and dopamine receptor D2/ ankyrin repeat and kinase domain containing one polymorphisms may play a role in emotion dysregulation. Inconsistent findings have been noted, possibly due to the heterogeneity in study designs and characteristics of different populations. Further research on the role of genetic predetermination of emotion dysregulation in children and adolescents is warranted.展开更多
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
文摘Vocalizations play a critical role in mate recognition and mate choice in a number of taxa, especially, but not limited to, orthopterans, frogs, and birds. But receivers can only recognize and prefer sounds that they can hear. Thus a fundamental question linking neurobiology and sexual selection asks-what is the threshold for detecting acoustic sexual displays? In this study, we use 3 methods to assess such thresholds in tdngara frogs: behavioral responses, auditory brainstem responsesz and multi unit electrophysiological recordi ngs from the midbrain.We show that thresholds are lowest for multiunit recordings (ca. 45 dB SPL), and then for behavioral responses (ca. 61 dB SPL), with auditory brainstem responses exhibiting the highest thresholds (ca. 71 dB SPL). We discuss why these estimates differ and why, as with other studies, it is unlikely that they should be the same. Although all of these studies estimate thresholds they are not measuring the same thresholds;behavioral thresholds are based on signal salienee whereas the 2 neural assays estimate physiological thresholds. All 3 estimates, however, make it clear that to have an appreciation for detection and salienee of acoustic signals we must listen to those signals through the ears of the receivers.
文摘Advancements in neuroscience research present opportunities and challenges,requiring substantial resources and funding.To address this,we describe here“Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT)”,an open-source,versatile,and cost-effective apparatus for intertemporal choice testing in rodents.This allows quantification of delay discounting(DD),a cross-species phenomenon observed in decision making which provides valuable insights into higher-order cognitive functioning.In DD,the subjective value of a delayed reward is reduced as a function of the delay for its receipt.Using our apparatus,we implemented an effective intertemporal choice paradigm for the quantification of DD based on an adjusting delayed amount(ADA)algorithm using mango juice as a reward.Our paradigm requires limited training,a few 3D-printed parts and inexpensive electrical components,including a Raspberry Pi control unit.Furthermore,it is compatible with several in vivo procedures and the use of nose pokes instead of levers allows for faster task learning.Besides the main application described here,the apparatus can be further extended to implement other behavioral tests and protocols,including standard operant conditioning.In conclusion,we describe a versatile and cost-effective design based on Raspberry Pi that can support research in animal behavior,decision making and,more specifically,delay discounting.
文摘The synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) was used to induce innate fear in male GAD67 mice and behavioral changes were correlated with c-fos mRNA levels as marker for neuronal activation to reveal underlying activated fear circuits. Results show the same amount of increased freezing and decreased rearing and grooming behavior of TMT-exposed GAD67 mice and wild type littermates, and therefore suggest that heterozygous knock-in of GFP in the GAD67 gene that is associated with a fifty percent decreased GAD67 protein level in the brain, has no impact on TMT-induced behavioral effects. Exposure to TMT significantly increased the number of c-fos mRNA positive cells in the main olfactory bulb (MOB), the lateral septum (LS), the bed nucleus of the stria terminalis (BNST), the central amygdala (CeA), the anterior-ventral (MeAav), the anterior-dorsal (MeAad) and the posterior-ventral (MeApv) part of the medial amygdala in GAD67 mice. Thus, to further investigate the role of GABAergic neurons in TMT-induced uncontrollable stress responses GAD67 mice that provide the advantage of prelabeled GABAergic neurons through the GABA neuron specific expression of GFP could be a suitable model organism.
基金supported by the National Natural Science Foundation of China(No.82072811).
文摘Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.
文摘BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different etiologies.The pathomechanisms of MH encompass various conditions.The etiological classification of MH is of particular importance and offers valuable insights to understand MH,and further to develop the effective treatment of MH.Over the recent decades,more MH cases have been reported,revealing newly identified medical and psychiatric causes of MH.Functional imaging studies reveal that MH activates a wide array of brain regions.An up-to-date analysis on MH,especially on MH comorbid psychiatric conditions is warranted.AIM To propose a new classification of MH;to study the age and gender differences of MH in mental disorders;and neuropathology of MH.METHODS Literatures searches were conducted using keywords such as“music hallucination,”“music hallucination and mental illness,”“music hallucination and gender difference,”and“music hallucination and psychiatric disease”in the databases of PubMed,Google Scholar,and Web of Science.MH cases were collected and categorized based on their etiologies.The t-test and ANOVA were employed(P<0.05)to compare the age differences of MH different etiological groups.Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed.RESULTS Among the 357 yielded publications,294 MH cases were collected.The average age of MH cases was 67.9 years,with a predominance of females(66.8%females vs 33.2%males).MH was classified into eight groups based on their etiological mechanisms.Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses.CONCLUSION We carried out a more comprehensive review of MH studies.For the first time according to our knowledge,we demonstrated the psychiatric conditions linked and/or associated with MH from statistical,biological and molecular point of view.
文摘Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.
文摘Given the failure to develop disease-modifying therapies for Alzheimer’s disease(AD),strategies aiming at preventing or delaying the onset of the disease are being prioritized.While the debate regarding whether depression is an etiological risk factor or a prodrome of AD rages on,a key determining factor may be the timing of depression onset in older adults.There is increasing evidence that untreated early-onset depression is a risk factor and that late-onset depression may be a catalyst of cognitive decline.Data from animal studies have shown a beneficial impact of selective serotonin reuptake inhibitors on pathophysiological biomarkers of AD including amyloid burden,tau deposits and neurogenesis.In humans,studies focusing on subjects with a prior history of depression also showed a delay in the onset of AD in those treated with most selective serotonin reuptake inhibitors.Paroxetine,which has strong anticholinergic properties,was associated with increased mortality and mixed effects on amyloid and tau deposits in mice,as well as increased odds of developing AD in humans.Although most of the data regarding selective serotonin reuptake inhibitors is promising,findings should be interpreted cautiously because of notable methodological heterogeneity between studies.There is thus a need to conduct large scale randomized controlled trials with long follow up periods to clarify the dose-effect relationship of specific serotonergic antidepressants on AD prevention.
基金supported in part by the National Natural Science Foundation of China(81271469 and 81471350)the Natural Science Foundation of Zhejiang Province,China(Z2101211 and Y20140692)a Medical Health Project of Zhejiang Province, China(2014KYB161)
文摘Abstract Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobi- ological mechanism underlying propofol reward is not fully understood. The purpose of this study was to inves- tigate the role of extracellular signal-regulated kinase （ERK） signal transduction pathways in the nucleus accumbens （NAc） in propofol self-administration. We tested the expression of p-ERK in the NAc following the maintenance of propofol self-administration in rats. We also assessed the effect of administration of SCH23390, an antagonist of the D1 dopamine receptor, on the expression of p-ERK in the NAc in propofol self-administering rats, and examined the effects of intra-NAc injection of U0126, an MEK inhibitor, on propofol reinforcement in rats. The results showed that the expression of p-ERK in the NAc increased significantly in rats maintained on propofol, and pre-treatment with SCH23390 inhibited the propofol self- administration and diminished the expression of p-ERK in the NAc. Moreover, intra-NAc injection of U0126 （4 μg/ side） attenuated the propofol self-administration. The data suggest that ERK signal transduction pathways coupledwith D1 dopamine receptors in the NAc may be involved in the maintenance of propofol self-administration and its rewarding effects.
基金Supported by In part by grants from the University of Missouri System,including the UM-Research Board and the Interdisciplinary Intercampus Research Program to GTTfrom the W.M. Keck Foundation to SEM
文摘A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments. Roots of the self-medication concept in psychiatry date back at least to the 1980 s. Observations that rates of smokers in schizophrenic patients are multiple times the rates for regular smoking in the general population, as well as those with other disorders, proved particularly tempting for a self-medication explanation. Additional evidence came from experiments with animal models exposed to nicotine and the identification of neurobiological mechanisms suggesting self-medication with smoking is a plausible idea. More recently, results from studies comparing smoking and non-smoking schizophrenic patients have led to the questioning of the self-medication hypothesis. Closer examination of the literature points to the possibility that smoking is less beneficial on schizophrenic symptomology than generally assumed while clearly increasing the risk of cancer and other smoking-related diseases responsible for early mortality. It is a good time to examine the evidence for the self-medication concept as it relates to smoking. Our approach is to focus on data addressing direct or implied predictions of the hypothesis in schizophrenic smokers.
基金Supported by NARSAD,Martek Biosciences IncThe Inflammation Research Foundation(IRF)+2 种基金Ortho-Mc Neil Janssen,Astra Zeneca,Eli Lillypreviously a member of the IRF scientific advisory board(Mc Namara RK)the Perinatal Institute at Cincinnati Children’s Hospital(Valentine CJ)
文摘Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.
文摘Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1(IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sexhormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinasesignaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar signaling cascades. Future research on both neuroprotection and diabetes should include androgens into the interplay of IGF1 and sex hormones.
基金supported by“Sapienza”University(Ateneo2021_RP12117A8857C5F8 to SC)。
文摘Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous system.In recent years,BDNF has received considerable attention for its importance in the development and maintenance of normal brain function.This is because BDNF plays an important role in crucial functions of the nervous system,such as the survival,differentiation,and maturation of neurons and glial cells as well as the actions of neuroprotection in adverse conditions,such as glutamatergic overstimulation,cerebral ischemia,hypoglycemia,and neurotoxicity(Kowiański et al.,2018).
基金supported by the Program of Medical Science of Ningbo Municipality,Zhejiang Province,China(2013A23)the Ningbo Municipal Innovation Team of Life Science and Health,Zhejiang Province,China(2015C110026)the National Natural Science Foundation of China(81501164 and81611130224)
文摘Patients with schizophrenia undergo changes in brain plasticity. In the present study, we characterized motor cortical-striatal plasticity in such patients. Compared with the potentiation following high-frequency repetitive transcranial magnetic stimulation in the control group, the patients demonstrated impaired plasticity of corticostriatal motor-evoked potentials recorded from hand muscles.Notably, the loss of cortical plasticity was correlated with impaired motor learning in a rotary pursuit task. Moreover,the loss of plasticity was correlated with the symptoms of schizophrenia. The results suggest that the progression of schizophrenia is accompanied by altered cortical plasticity and functioning.
文摘Alzheimer＇s disease is the most common neurodegenerative disorder and no disease-modifying treatment is currently available.Research has shown that while brain neurogenesis continues in adult life,it declines with age.Using parabiosis,plasma transfusions and direct administration of neural growth factors,animal studies have demonstrated the positive impact of exposure to young blood products on neurogenesis and synaptic plasticity in an aging brain.The hippocampus and the sub-ventricular zones were identified as the main regions affected.Promising findings have prompted researchers to experiment their effects in subjects with an established neurocognitive disorder,such as Alzheimer＇s disease.They argued that modification of brain vasculature,reactivation of adult neural stem cells,and remodeling of their synaptic activity/plasticity may lead to cognitive enhancement and increased neurogenesis.One pilot human study found that young donor plasma infusion protocols for adults with Alzheimer＇s disease were safe and feasible;however,no statistically significant improvements in cognition were detected.There is a need to conduct additional placebo-controlled human studies in larger samples.Future studies should focus on identifying an “optimal age” at which an intervention in humans may yield significant cognitive enhancement,as well as determining the types of transfusions with the best efficacy and tolerability profiles.
文摘Acoustic communication in many anuran species can show the effects of both natural and sexual selection. This is reflected in the sexually dimorphic an atomy of the lary nx and ear structures, as well as the allometric relationship of these morphological traits to head or body size. In this study, we examined laryngeal and ear structures of cricket frogs Acris crepitans not only as sexually dimorphic characteristics, but also as they differ across populations in environmentally different habitats. We used 2-way ANOVA to determine whether the volumetric or linear measurements of these structures differed by sex and population. Females have significantly larger body, head, and ear sizes, but significantly smaller larynges than males. Furthermore, females as well as males show larger body and head sizes, ears, and larynges in a dryer open habitat. An ANCOVA analysis shows that males, but not females, differ in laryngeal size across populations beyond the allometric changes attributable to head size alone indicating that males have a greater degree of laryngeal population variation. In contrast, our covariate analysis found that in both sexes many of the ear differences are non-sigrdficant once head size is accounted for, suggesting that most of the population-level ear variation is due to allometric effects of body size. We conclude that although both sexes show size differences in the larynx related to selection for larger body size in dry, open habitats, selection on males for larger larynx size related to the production of lower frequency calls in those habitats does not result in correlated changes in the female larynx. The results suggest that in anurans, selection for changes in body and head size affects both sexes equally, male calls and the vocal structures responsible for them can further diversify without concordant changes in females.
基金supported by the National Basic Research Program of China(2015CB553504)the National Natural Science Foundation of China(81471350 and 81671321)the Natural Science Foundation of Ningbo Municipality,Zhejiang Province,China(2015A610193)
文摘Activation of presynaptic group II metabotropic glutamate receptors（mGluR2/3） inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate（NAAG）, an agonist of endogenous mGluR2/3,in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroinseeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1（FR1） schedule for 10 days,then received NAAG（50 or 100μg/10 μL in each nostril）in the absence or presence of LY341495（1 mg/kg, i.p.）, an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin selfadministration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroinpriming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG,via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.
基金Science Foundation of Ministry of Education of China,No.FBB011469Hangzhou Municipal Natural Science Foundation, No.0737XP39Foundation of Hong Kong Special Administrative Region(RGC)
文摘The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.
文摘Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefore, agent(s) capable of inhibiting brain amyloid deposition might delay the occurrence or retard the progress forwards of AD and related neurobehavioral symptoms. Here, we report whether, chronic oral administration of Syzygium cumini (locally known as Jam)-seed extract exerts protection against the progressive cognitive decline in the Aβ1-40-infused AD model rats. After 12 weeks of feeding with S. cumini seed extract (at 300 mg/kg BW), we evaluated the learning-related memory of the rats by 8-arm radial maze task, where we determined two types of memory errors, namely reference memory errors (RMEs) and working memory errors (WMEs). After completion of memory tests, rats were sacrificed and the levels of lipid peroxide (LPO), the Aβ1-40-burden, Aβ1-40-oligomers, proinflammatory TNFα, brain derived neurotrophic factor (BDNF), Tyrosine-kinase B (TrkB), postsynaptic-density protein 95 (PSD-95) and Synapse-associated protein (SNAP-25) were determined in the corticohippocampal tissues of the brain. In addition, in vitro antioxidative effects of S. cumini seed extract were evaluated. The oral administration of S. cumini extract significantly increased the memory-related learning ability of the AD model rats, concomitantly with reductions in the levels of corticohippocampal Aβ1-40-burden and Aβ1-40-oligomers. Furthermore, the extract suppressed the levels of TNFα and LPO in the corticohippocampal tissues of the AD rats and also the later in the plasma, suggesting an anti-oxidative and anti-inflammatory activities of the S. cumini extract in the brains of AD model rats. S. cumini extract also increased the levels of brain cognition and memory-related proteins, including BDNF, TrKB, PSD-95 and SNAP-25. We thus suggest that S. cumini-seed extract could be used in neurobehavioral deficits and associated pathogenesis of Alzheimer’s disease.
基金Supported by Oxley Foundation(Lin PI and Barzman D)Center for Clinical and Translational Science and Training(Barzman D)American Physician Institute(Geise C)
文摘Previous evidence suggests that emotion dysregulation may have different biological correlates between adults and children/adolescents. Although the role of genetic factors has been extensively studied in adult-onset emotion dysregulation, the genetic basis for pediatriconset emotion dysregulation remains elusive. The current review article presents a summary of previous studies that have suggested a few genetic variants associated with pediatric emotion dysregulation. Among these candidate loci, many prior studies have been focused on serotonin transporter promoter gene polymorphism 5-HTTLPR. Certain alleles of the 5-HTTLPR gene polymorphism have been found to be associated with traits associated with emotion dysregulation, such as aggression, affect reactivity, and insecure attachment. Additionally, genetic variants involving dopamine and neurophysiological biomarkers like the COMT Val158Met(rs460) and dopamine receptor D2/ ankyrin repeat and kinase domain containing one polymorphisms may play a role in emotion dysregulation. Inconsistent findings have been noted, possibly due to the heterogeneity in study designs and characteristics of different populations. Further research on the role of genetic predetermination of emotion dysregulation in children and adolescents is warranted.
