The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
Chinese cabbage(Brassica rapa subsp.pekinensis)is a widely cultivated vegetable crop in Asia with significant economic importance(Li et al.,2024;Yu et al.,2024).As a potyvirus with the broad host range,turnip mosaic v...Chinese cabbage(Brassica rapa subsp.pekinensis)is a widely cultivated vegetable crop in Asia with significant economic importance(Li et al.,2024;Yu et al.,2024).As a potyvirus with the broad host range,turnip mosaic virus(TuMV)is a major pathogen affecting Chinese cabbages,leading to severe yield losses(Li et al.,2019).Traditional control measures have shown limited efficacy,and the long-term use of chemical pesticides has led to significant issues such as environmental pollution and pathogen resistance(Samara et al.,2021;Lu et al.,2022).Biologicallyderived pesticides have garnered considerable attention owing to their eco-friendly attributes(Ayilara et al.,2023).γ-Aminobutyric acid(GABA),initially discovered in potato tubers,has been proven to regulate immune responses and enhance resistance to fungal and bacterial pathogens by modulating reactive oxygen species and stress-related hormone signals(Tarkowski et al.,2020;Wang et al.,2025).But biologically-derived agents typically face challenges such as large particle size and instability,which limit their practical application and bioavailability(Daraban et al.,2023).展开更多
Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cyperm...Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cypermethrin (70 mg/kg, i.p) once a day for 3 days. Glu and GABA immunoreactive cells and transmitters in CNS were studied by immunohistochemical method. Results\ The total number, percentage of positive area and integral optical density of glutamate immunoreactive cell in cerebral cortex, hippocampus decreased significantly in permethrin or cypermethrin, while GABA was enhanced. Cypermethrin is more tent than permethrin on either Glu or GABA. Conclusion\ Disturbance of Glu and GABA is likely to play a role in the development of pyrethroids excitatory neurotoxicity.展开更多
Post-traumatic stress disorder(PTSD)remains a debilitating psychiatric condition with limited pharmacological treatment options.Identifying novel therapeutic targets is critical for addressing its unmet clinical needs...Post-traumatic stress disorder(PTSD)remains a debilitating psychiatric condition with limited pharmacological treatment options.Identifying novel therapeutic targets is critical for addressing its unmet clinical needs.Through our comprehensive human clinical research,including both cross-sectional and longitudinal studies,we revealed a compelling link between dysregulated prefrontal gamma-aminobutyric acid(GABA)levels and PTSD symptoms.Notably,elevated prefrontal GABA levels in PTSD patients are associated with impaired cerebral blood flow(CBF)and symptom severity,normalizing with recovery,highlighting GABA dysregulation as a key mechanism in the disorder.Postmortem and PTSD-like mouse models implicated monoamine oxidase B(MAOB)-dependent astrocytic GABA as a primary driver of this imbalance,exacerbating deficit in fear extinction retrieval.展开更多
Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system(CNS)injury.The glial scar has been proposed as a major contributor to this failure in the ...Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system(CNS)injury.The glial scar has been proposed as a major contributor to this failure in the regenerative process.However,its underlying molecular and cellular mechanisms remain unclear.Here,we report that monoamine oxidase B(MAOB)-dependent excessiveγ-aminobutyric acid(GABA)release from reactive astrocytes suppresses the CNS repair system by reducing brain‒derived neurotrophic factor(BDNF)and tropomyosin receptor kinase B(TrkB)expression in severe spinal cord injury(SCI)animal models.Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery.Notably,the selective MAOB inhibitor,KDS2010,facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model.Its dose-dependent effects were further validated in a monkey SCI model.Moreover,KDS2010 demonstrated a tolerable safety profile and doseproportional pharmacokinetics in healthy humans during a phase 1 clinical trial.This pathway therefore represents a pivotal target for overcoming the intrinsic barriers to CNS repair after injury.Our findings identify the astrocytic MAOB‒GABA axis as a crucial molecular and cellular brake on the CNS repair system following SCI and highlight the translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment.展开更多
Background We investigated the co-expression of calb indin-D28k (CB), calretinin (CR) and parvalbumin (PV, a combination of the three is referred to as CaBPs) with γ-aminobutyric acid (GABA) or glycine in neurons of ...Background We investigated the co-expression of calb indin-D28k (CB), calretinin (CR) and parvalbumin (PV, a combination of the three is referred to as CaBPs) with γ-aminobutyric acid (GABA) or glycine in neurons of the rat medullary dorsal horn (MDH).Methods Immunofluorescence histochemical double-staining for CaBPs and GABA or glycine was performed on the sections from rat MDH. Results CB-, CR-, PV-, GABA- and glycine-like immunoreactive (LI) neurons were differentially observed in all layers of the MDH, but particularly in lamina Ⅱ. Neurons that exhibited immunoreactivity for both CaBPs and GABA or glycine were also observed mainly in lamina Ⅱ. A few of them were found in laminae I and III. The percentages of neurons which co-expressed CB/GABA or CB/glycine out of the total numbers of CB- and GABA-LI neurons or CB- and glycine-LI neurons were 5.3% and 12.1% or 4.1% and 10.0%, respectively. The ratios of CR/GABA or CR/glycine co-existing neurons out of the total numbers of CR- and GABA-LI neurons or CR- and glycine-LI neurons were 5.8% and 7.6% or 4.4% and 7.1%, respectively. The rates of PV/GABA or PV/glycine co-localized neurons out of the total numbers of PV- and GABA-LI neurons or PV- and glycine-LI neurons were 11.1% and 5.1% or 9.9% and 5.1%, respectively. Conclusion The results indicate that some neurons in the MDH contain both CaBPs and GABA or glycine.展开更多
Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows...Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.展开更多
Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a c...Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a case of anti-GABA-B receptor encephalitis in a 57-year-old man who presented with seizures,memory loss,and abnormal behavior.He developed partially neurological responses to immunotherapy,but refused comprehensive tumor screening.The symptoms were aggravated again 4 months later.Workup showed antibodies to GABA-B receptors and tumor screening revealed SCLC.It highlights the importance of early screening of underlying tumor and anti-tumor treatment in paraneoplastic cases.展开更多
BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impa...BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.展开更多
A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spo...A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spontaneous regeneration.We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration.We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A(GABAA)receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration,as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells.Here,we show that inhibition of a pharmacologically distinct subset of GABAA receptors(GABAA-ρ)can also induce retina regeneration.Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration.Gene expression analyses indicate that inhibition of GABAA-ρreceptors induces a canonical retinal regenerative response.Our results support a model in which decreased levels of GABA,such as would occur after retinal cell death or damage,induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration.Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee(Protocol M1800200)on January 29,2019.展开更多
The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neu...The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.展开更多
The interaction between amino acid drugs, aminobutyric acid, carbocisteine and levodopa, with chloranil was studied spectrophotometrically. The conditions were investigated and optimized. The interaction obeyed Beer＇...The interaction between amino acid drugs, aminobutyric acid, carbocisteine and levodopa, with chloranil was studied spectrophotometrically. The conditions were investigated and optimized. The interaction obeyed Beer＇s law over the range of 0.2-8.7, 1.2-20 and 2-26.4 μg/mL for aminobutyric acid, carbocisteine and levodopa, respectively. The validity was compared with that by the official methods^1,3,5 and the recovery studies of standard addition method, the result is satisfactory. The proposed method has been successfully applied to the determination of the above drugs in tablets.展开更多
We investigated the distribution of gamma aminobutyric acid, tyrosine hydroxylase and nitric oxide-producing elements in a cherry salmon Oncorhynchus masou brain at various stages of postnatal ontogenesis by immunohis...We investigated the distribution of gamma aminobutyric acid, tyrosine hydroxylase and nitric oxide-producing elements in a cherry salmon Oncorhynchus masou brain at various stages of postnatal ontogenesis by immunohistochemical staining and histochemical staining. The periventricular region cells exhibited the morphology of neurons and glia including radial glia-like cells and contained several neurochemical substances. Heterogeneous populations of tyrosine hydroxylase-, gamma aminobutyric acid-immunoreactive, as well as nicotinamide adenine dinucleotide phosphate diaphorase-positive cells were observed in proliferating cell nuclear antigen-immunoreactive proliferative zones in periventricular area of diencephalon, central grey layer of dorsomedial tegmentum, medulla and spinal cord. Immunolocalization of Pax6 in the cherry salmon brain revealed a neuromeric construction of the brain at various stages of postnatal ontogenesis, and this was confirmed by tyrosine hydroxylase and gamma aminobutyric acid labeling.展开更多
OBJECTIVE:To observe the effect of Pingan Fang(PG)on behavioral sensitization and conditioned place preference(CPP)induced by ethanol in mice,and to determine the intervention mechanism of PG on alcohol addiction.METH...OBJECTIVE:To observe the effect of Pingan Fang(PG)on behavioral sensitization and conditioned place preference(CPP)induced by ethanol in mice,and to determine the intervention mechanism of PG on alcohol addiction.METHODS:A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice.The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol.Concentrations of dopamine(DA),Glutamate(Glu),and?-aminobutyric acid(GABA)in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay.RESULTS:Although PG did not alter spontaneous activity in mice,it reduced the growth of spontaneous activity stimulated by ethanol.The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased.CONCLUSION:Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice.The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system.This suggests that PG might be useful for the prevention and treatment of alcohol addiction.展开更多
Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject t...Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters （inhibitory GABA transporters GAT and excitatory glutamate transporters GT）. Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter （GLT） is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.展开更多
Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known f...Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.展开更多
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
基金supported by the National Natural Science Foundation of China(Grant Nos.32402564,32330096,32372631)Hebei Natural Science Foundation(Grant No.C2024204246)+1 种基金the Pinduoduo-China Agricultural University Research Fund(Grant No.PC2023B02018)the 2115 Talent Development Program of China Agricultural University.
文摘Chinese cabbage(Brassica rapa subsp.pekinensis)is a widely cultivated vegetable crop in Asia with significant economic importance(Li et al.,2024;Yu et al.,2024).As a potyvirus with the broad host range,turnip mosaic virus(TuMV)is a major pathogen affecting Chinese cabbages,leading to severe yield losses(Li et al.,2019).Traditional control measures have shown limited efficacy,and the long-term use of chemical pesticides has led to significant issues such as environmental pollution and pathogen resistance(Samara et al.,2021;Lu et al.,2022).Biologicallyderived pesticides have garnered considerable attention owing to their eco-friendly attributes(Ayilara et al.,2023).γ-Aminobutyric acid(GABA),initially discovered in potato tubers,has been proven to regulate immune responses and enhance resistance to fungal and bacterial pathogens by modulating reactive oxygen species and stress-related hormone signals(Tarkowski et al.,2020;Wang et al.,2025).But biologically-derived agents typically face challenges such as large particle size and instability,which limit their practical application and bioavailability(Daraban et al.,2023).
文摘Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cypermethrin (70 mg/kg, i.p) once a day for 3 days. Glu and GABA immunoreactive cells and transmitters in CNS were studied by immunohistochemical method. Results\ The total number, percentage of positive area and integral optical density of glutamate immunoreactive cell in cerebral cortex, hippocampus decreased significantly in permethrin or cypermethrin, while GABA was enhanced. Cypermethrin is more tent than permethrin on either Glu or GABA. Conclusion\ Disturbance of Glu and GABA is likely to play a role in the development of pyrethroids excitatory neurotoxicity.
基金supported by National Research Foundation of Korea grants funded by the Ministry of Science and ICT(RS-2024-00457381 to I.K.L.2020M3E5D9079742 to H.R.)+2 种基金by the Ministry of Education(2020R1A6A1A03043528 to I.K.L.)This work was also in part supported by the Institute for Basic Science(IBS),Center for Cognition and Sociality(IBS-R001-D2 to C.J.L)This project applied tools developed under NIH grants R01 EB016089,R01 EB023963 and P41 EB031771.
文摘Post-traumatic stress disorder(PTSD)remains a debilitating psychiatric condition with limited pharmacological treatment options.Identifying novel therapeutic targets is critical for addressing its unmet clinical needs.Through our comprehensive human clinical research,including both cross-sectional and longitudinal studies,we revealed a compelling link between dysregulated prefrontal gamma-aminobutyric acid(GABA)levels and PTSD symptoms.Notably,elevated prefrontal GABA levels in PTSD patients are associated with impaired cerebral blood flow(CBF)and symptom severity,normalizing with recovery,highlighting GABA dysregulation as a key mechanism in the disorder.Postmortem and PTSD-like mouse models implicated monoamine oxidase B(MAOB)-dependent astrocytic GABA as a primary driver of this imbalance,exacerbating deficit in fear extinction retrieval.
基金supported by a faculty research grant from Yonsei University College of Medicine(6-2018-0161)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00341308)+1 种基金the Center for Cognition and Sociality from Institute for Basic Science(IBS)(IBS-R001-D2)and NeuroBiogen Co.,LTD.
文摘Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system(CNS)injury.The glial scar has been proposed as a major contributor to this failure in the regenerative process.However,its underlying molecular and cellular mechanisms remain unclear.Here,we report that monoamine oxidase B(MAOB)-dependent excessiveγ-aminobutyric acid(GABA)release from reactive astrocytes suppresses the CNS repair system by reducing brain‒derived neurotrophic factor(BDNF)and tropomyosin receptor kinase B(TrkB)expression in severe spinal cord injury(SCI)animal models.Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery.Notably,the selective MAOB inhibitor,KDS2010,facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model.Its dose-dependent effects were further validated in a monkey SCI model.Moreover,KDS2010 demonstrated a tolerable safety profile and doseproportional pharmacokinetics in healthy humans during a phase 1 clinical trial.This pathway therefore represents a pivotal target for overcoming the intrinsic barriers to CNS repair after injury.Our findings identify the astrocytic MAOB‒GABA axis as a crucial molecular and cellular brake on the CNS repair system following SCI and highlight the translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment.
文摘Background We investigated the co-expression of calb indin-D28k (CB), calretinin (CR) and parvalbumin (PV, a combination of the three is referred to as CaBPs) with γ-aminobutyric acid (GABA) or glycine in neurons of the rat medullary dorsal horn (MDH).Methods Immunofluorescence histochemical double-staining for CaBPs and GABA or glycine was performed on the sections from rat MDH. Results CB-, CR-, PV-, GABA- and glycine-like immunoreactive (LI) neurons were differentially observed in all layers of the MDH, but particularly in lamina Ⅱ. Neurons that exhibited immunoreactivity for both CaBPs and GABA or glycine were also observed mainly in lamina Ⅱ. A few of them were found in laminae I and III. The percentages of neurons which co-expressed CB/GABA or CB/glycine out of the total numbers of CB- and GABA-LI neurons or CB- and glycine-LI neurons were 5.3% and 12.1% or 4.1% and 10.0%, respectively. The ratios of CR/GABA or CR/glycine co-existing neurons out of the total numbers of CR- and GABA-LI neurons or CR- and glycine-LI neurons were 5.8% and 7.6% or 4.4% and 7.1%, respectively. The rates of PV/GABA or PV/glycine co-localized neurons out of the total numbers of PV- and GABA-LI neurons or PV- and glycine-LI neurons were 11.1% and 5.1% or 9.9% and 5.1%, respectively. Conclusion The results indicate that some neurons in the MDH contain both CaBPs and GABA or glycine.
基金supported by the Shanghai Science&Technology Commission(18140902502)the National Key Research and Development Program of China(2016YFC1303100)+2 种基金the National Natural Science Foundation of China(81472423)the Shanghai Clinical and Medical Center of Key Program(2017ZZ01016)the Shanghai Science and Technology Innovation Project of Traditional Chinese Medicine(ZYKC201701020).
文摘Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.
文摘Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a case of anti-GABA-B receptor encephalitis in a 57-year-old man who presented with seizures,memory loss,and abnormal behavior.He developed partially neurological responses to immunotherapy,but refused comprehensive tumor screening.The symptoms were aggravated again 4 months later.Workup showed antibodies to GABA-B receptors and tumor screening revealed SCLC.It highlights the importance of early screening of underlying tumor and anti-tumor treatment in paraneoplastic cases.
文摘BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.
基金grants from the NIH R01EY024354-S1 and UO1 EY027265 to JGPand T32 EY021453additional support from the Stevenson family and Gisela Mosig endowments to Vanderbilt University。
文摘A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spontaneous regeneration.We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration.We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A(GABAA)receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration,as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells.Here,we show that inhibition of a pharmacologically distinct subset of GABAA receptors(GABAA-ρ)can also induce retina regeneration.Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration.Gene expression analyses indicate that inhibition of GABAA-ρreceptors induces a canonical retinal regenerative response.Our results support a model in which decreased levels of GABA,such as would occur after retinal cell death or damage,induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration.Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee(Protocol M1800200)on January 29,2019.
基金Supported by National Institutes of Health,No.R01NS091542National Natural Science Foundation of China,No.81771149,No.U1704165。
文摘The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.
文摘The interaction between amino acid drugs, aminobutyric acid, carbocisteine and levodopa, with chloranil was studied spectrophotometrically. The conditions were investigated and optimized. The interaction obeyed Beer＇s law over the range of 0.2-8.7, 1.2-20 and 2-26.4 μg/mL for aminobutyric acid, carbocisteine and levodopa, respectively. The validity was compared with that by the official methods^1,3,5 and the recovery studies of standard addition method, the result is satisfactory. The proposed method has been successfully applied to the determination of the above drugs in tablets.
基金supported by a grant from Far Eastern Branch of Russian Academy of Sciences, No.12-Ⅲ-A-06-095
文摘We investigated the distribution of gamma aminobutyric acid, tyrosine hydroxylase and nitric oxide-producing elements in a cherry salmon Oncorhynchus masou brain at various stages of postnatal ontogenesis by immunohistochemical staining and histochemical staining. The periventricular region cells exhibited the morphology of neurons and glia including radial glia-like cells and contained several neurochemical substances. Heterogeneous populations of tyrosine hydroxylase-, gamma aminobutyric acid-immunoreactive, as well as nicotinamide adenine dinucleotide phosphate diaphorase-positive cells were observed in proliferating cell nuclear antigen-immunoreactive proliferative zones in periventricular area of diencephalon, central grey layer of dorsomedial tegmentum, medulla and spinal cord. Immunolocalization of Pax6 in the cherry salmon brain revealed a neuromeric construction of the brain at various stages of postnatal ontogenesis, and this was confirmed by tyrosine hydroxylase and gamma aminobutyric acid labeling.
基金Supported by Grants from The Administration of Traditional Chinese Medicine Sichuan Province(Exploration of Molecular Mechanisms of Fuyangfang Which Based on the TCM Theory of Yang Deficiency Qi Qie about Alcohol Addiction about Alcohol Addiction Memory and Eliminate,No.2014-E-069)
文摘OBJECTIVE:To observe the effect of Pingan Fang(PG)on behavioral sensitization and conditioned place preference(CPP)induced by ethanol in mice,and to determine the intervention mechanism of PG on alcohol addiction.METHODS:A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice.The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol.Concentrations of dopamine(DA),Glutamate(Glu),and?-aminobutyric acid(GABA)in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay.RESULTS:Although PG did not alter spontaneous activity in mice,it reduced the growth of spontaneous activity stimulated by ethanol.The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased.CONCLUSION:Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice.The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system.This suggests that PG might be useful for the prevention and treatment of alcohol addiction.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81171053）.
文摘Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters （inhibitory GABA transporters GAT and excitatory glutamate transporters GT）. Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter （GLT） is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.
文摘Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.
