Neuroimmune system may be involved in the pathological process of bipolar disorder(BD),but the essential association is not fully understood.Accumulating evidence has shown that BD involves the activation of immune ce...Neuroimmune system may be involved in the pathological process of bipolar disorder(BD),but the essential association is not fully understood.Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system(CNS).Meanwhile,neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized,such as neurotransmitter systems,neuroendocrine systems,neurotrophic factors,and oxidative stress.Simultaneously,related genes and immune changes in peripheral blood vary with it.Overall,neuroimmunity may play an important role in the pathogenesis of BD,and the inflammatory cytokines,especially interleukin-6 and tumor necrosis factor-alpha,have potential value for the clinical diagnosis and prognosis of BD,as well as predicting the therapeutic effects of drugs.Large-scale studies are needed to extend the evidence on neuroimmunity in BD,and to examine its clinical value for applications such as early prediction and treatment.展开更多
Pulsed microwaves are widely used inradar,navigation, and communication. The average power density is low at narrow pulse widths or large pulse intervals,but pulsed microwaves at certain peak densities exert numerous ...Pulsed microwaves are widely used inradar,navigation, and communication. The average power density is low at narrow pulse widths or large pulse intervals,but pulsed microwaves at certain peak densities exert numerous biological effects, including展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
AIM:To analyze visual dysfunction in rats under simulated weightlessness(SW)by examining trans-laminar cribrosa pressure difference(TLCPD)and neuroimmune responses.METHODS:The 72 male Sprague-Dawley rats were randomly...AIM:To analyze visual dysfunction in rats under simulated weightlessness(SW)by examining trans-laminar cribrosa pressure difference(TLCPD)and neuroimmune responses.METHODS:The 72 male Sprague-Dawley rats were randomly assigned into two groups(ground control and hindlimb unloading-simulated microgravity)using stratified randomization,with each group further subdivided into three exposure durations:SW 2-week(SW-2W),4-week(SW-4W),and 8-week(SW-8W),n=12 per subgroup.At the designated time points for each group,intraocular pressure(IOP)and intracranial pressure(ICP)were measured,and the trans-laminar cribrosa pressure difference(TLCPD)was calculated.Additionally,optomotor response(OMR),electroretinography(ERG),and optical coherence tomography(OCT)were performed.The number of retinal ganglion cells(RGCs)was quantified via immunofluorescence,the activation of astrocytes and microglial cells was determined,and Sholl analysis was conducted to assess the function and morphology of microglial cells.Data were analyzed with SPSS and GraphPad Prism(P<0.05).RESULTS:Under prolonged simulated microgravity,rats exhibited a progressive increase in both IOP and ICP,with the most pronounced rise observed at 8wk.Concurrently,the TLCPD shifted from a negative value in controls to a positive value.These pressure alterations were associated with retinal dysfunction,as evidenced by significant reductions in ERG b-wave and photopic negative response(PhNR)amplitudes.OCT and histological analyses revealed subtle photoreceptor layer damage:while the inner nuclear layer(INL)thickness remained relatively unchanged,the outer nuclear layer(ONL)thinned significantly,and the nerve fiber layer-ganglion cell layer complex thickness(NFL-GCL)complex initially thickened before later thinning.Immunofluorescence further demonstrated marked neuroimmune activation,with astrocytes transitioning from having large cell bodies with small,elongated,sparse processes to a phenotype characterized by compact,enlarged nuclei and aggregated processes,alongside notable RGC loss.CONCLUSION:Based on the results from the simulated microgravity rat model,microgravity-induced changes in dual-chamber pressure,and neuroimmune responses in the retina may play a key role in visual dysfunction.Specifically,the activation of retinal neuroimmune cells(astrocytes and microglial cells)induced by mechanical stress appears to be central to retinal and optic nerve damage.展开更多
The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. Fo...The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.展开更多
Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs freq...Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs frequently coexist with liver diseases,including cirrhosis,thereby exacerbating clinical manifestations and complicating management;this overlap is underpinned by shared mechanisms,including gut dysbiosis,increased intestinal permeability,systemic inflammation,and altered neuroimmune signaling.Portal hypertension in cirrhosis promotes small intestinal bacterial overgrowth and microbial translocation,thereby triggering inflammatory pathways that worsen gut and liver function.This minireview explores the gut-liver axis as a central mediator in the interplay between DGBIs and liver disease/cirrhosis.Clinically,these interactions manifest as refractory gastrointestinal symptoms,nutritional deficiencies,and impaired quality of life.Emerging research emphasizes the need for integrative diagnostic approaches,such as combining advanced imaging,microbiome analysis,and biomarker profiling,to unravel the complex interplay between DGBIs and liver disease/cirrhosis.Therapeutic interventions targeting the gut microbiome,neuroimmune pathways,and lifestyle modification can mitigate disease burden.This review underscores the importance of a multidisciplinary framework for enhancing patient outcomes and guiding future research in this intersectional field.展开更多
Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious a...Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.展开更多
Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and...Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Gulf War Illness(GWI)is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms.Among these gastrointestinal symptoms,motility disorders are highly prevalent,presenting as chronic...Gulf War Illness(GWI)is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms.Among these gastrointestinal symptoms,motility disorders are highly prevalent,presenting as chronic constipation,stomach pain,indigestion,diarrhea,and other conditions that severely impact the quality of life of GWI veterans.However,despite a high prevalence of gastrointestinal impairments among these veterans,most research attention has focused on neurological disturbances.This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI.Generally,these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI.Additionally,this perspective highlights the potential and challenges of in vitro bioengineering models,which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.展开更多
Neuroimmune disorders,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,and Guillain–Barrésyndrome,are characterized by the dysfunction of both the immune system and the nervous...Neuroimmune disorders,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,and Guillain–Barrésyndrome,are characterized by the dysfunction of both the immune system and the nervous system.Increasing evidence suggests that extracellular vesicles and autophagy are closely associated with the pathogenesis of these disorders.In this review,we summarize the current understanding of the interactions between extracellular vesicles and autophagy in neuroimmune disorders and discuss their potential diagnostic and therapeutic applications.Here we highlight the need for further research to fully understand the mechanisms underlying these disorders,and to develop new diagnostic and therapeutic strategies.展开更多
The investigative evidence and emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many of the f...The investigative evidence and emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many of the functional gastrointestinal disorders. Neurogastroenterological research aims for improved understanding of the physiology and pathophysiology of the digestive subsystems from which the arrays of functional symptoms emerge. The key subsystems for defecation-related symptoms and visceral hyper- sensitivity are the intestinal secretory glands, the musculature and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts for the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication and the brain-gut axis.展开更多
Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunicat...Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory functionand pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit comorbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI展开更多
Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis,but they also contribute to various neurological disorders,including neurotrauma,stroke,and demyelinating or neuro...Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis,but they also contribute to various neurological disorders,including neurotrauma,stroke,and demyelinating or neurodegenerative diseases.Immune mechanisms in the central nervous system and periphery are regulated by a diverse group of endogenous proteins,which can be broadly divided into the pro-inflammatory damageassociated molecular patterns(DAMPs)and anti-inflammatory resolution-associated molecular patterns(RAMPs),even though there is notable overlap between the DAMPand RAMP-like activities for some of these molecules.Both groups of molecular patterns were initially described in peripheral immune processes and pathologies;however,it is now evident that at least some,if not all,of these immunomodulators also regulate neuroimmune processes and contribute to neuroinflammation in diverse central nervous system disorders.The review of recent literature demonstrates that studies on DAMPs and RAMPs of the central nervous system still lag behind the much broader research effort focused on their peripheral counterparts.Nevertheless,this review also reveals that over the last five years,significant advances have been made in our understanding of the neuroimmune functions of several well-established DAMPs,including high-mobility group box 1 protein and interleukin 33.Novel neuroimmune functions have been demonstrated for other DAMPs that previously were considered almost exclusively as peripheral immune regulators;they include mitochondrial transcription factor A and cytochrome C.RAMPs of the central nervous system are an emerging area of neuroimmunology with very high translational potential since some of these molecules have already been used in preclinical and clinical studies as candidate therapeutic agents for inflammatory conditions,such as multiple sclerosis and rheumatoid arthritis.The therapeutic potential of DAMP antagonists and neutralizing antibodies in central nervous system neuroinflammatory diseases is also supported by several of the identified studies.It can be concluded that further studies of DAMPs and RAMPs of the central nervous system will continue to be an important and productive field of neuroimmunology.展开更多
The aim of this study was to examine the immunomodulatory role of the unilateral ambiguous nucleus （Amb）. We performed electrical stimulation of the unilateral Amb, electrical stimulation of the left parietal cortex...The aim of this study was to examine the immunomodulatory role of the unilateral ambiguous nucleus （Amb）. We performed electrical stimulation of the unilateral Amb, electrical stimulation of the left parietal cortex and the lateral hypothalamus following unilateral Arab lesion, as well as microinjection of acetylcholine chloride and hemicholine-3 into the unilateral Amb, and electrical stimulation of the unilateral Amb after injection of atropine, mecamylamine, propranolol, and phentolamine. Results showed that the number and proliferation of peripheral blood T lymphocytes were increased after electrical stimulation of the unilateral Arab. The cholinergic neurons in the Amb released choline substances to alter cellular immunity, thus confirming that the Amb mediates the neuro-immunomodulatory process.展开更多
Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the i...Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the interaction between the nervous and immune systems.As first responders to stress,mast cells can initiate,amplify and prolong neuroimmune responses upon activation.Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells.Corticotropin-releasing hormone can stimulate mast cell activation,influence the activation of immune cells by peripheral nerves and modulate neuroimmune interactions.The latest evidence shows that the release of corticotropin-releasing hormone induces the degranulation of mast cells under stress conditions,leading to disruption of the bloodbrain barrier,which plays an important role in neurological diseases,such as Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,autism spectrum disorder and amyotrophic lateral sclerosis.Recent studies suggest that stress increases intestinal permeability and disrupts the blood-brain barrier through corticotropin-releasing hormone-mediated activation of mast cells,providing new insight into the complex interplay between the brain and gastrointestinal tract.The neuroimmune target of mast cells is the site at which the corticotropin-releasing hormone directly participates in the inflammatory responses of nerve terminals.In this review,we focus on the neuroimmune connections between corticotropin-releasing hormone and mast cells,with the aim of providing novel potential therapeutic targets for inflammatory,autoimmune and nervous system diseases.展开更多
Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic facto...Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.展开更多
Coronavirus disease 2019(COVID-19)has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide.Among the infected patients,there is a high prevalence of COVID-19-relat...Coronavirus disease 2019(COVID-19)has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide.Among the infected patients,there is a high prevalence of COVID-19-related cardiovascular injuries.However,the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear.The COVID-19 pandemic also has exacerbated the mental health burden of humans.Considering the close association between neuroimmune interactions and cardiovascular disease,this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease.It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage.Specifically,the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal(HPA)axis,sympathovagal imbalance,and endothelial dysfunction,which lead to an increased risk of developing cardiovascular injury during COVID-19.Therefore,during the prevention and treatment of cardiovascular complications in COVID-19 patients,particular attention should be given to relieve the mental health burden of these patients.展开更多
BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in T...BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.展开更多
Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activati...Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activation on the offspring’s neuroimmune function. The offspring born to dams treated with saline or lipopolysaccharide (LPS) at gestational day 18 was stimulated with saline or LPS at postnatal day 21, and the mRNA expression of various inflammatory genes in different brain regions of the offspring was analyzed. The offspring born to saline-treated dams exhibited a typical neuroimmune response with elevated levels of cytokines and chemokines following LPS stimulation in all four brain regions examined. In contrast, the offspring born to LPS- treated dams exhibited significantly reduced mRNA induction of cytokines and chemokines following LPS stimulation in the prefrontal cortex but not in the brainstem when compared with pups born to saline-treated dams. Furthermore, the mRNA expression of LPS-induced I-κBζ was significantly attenuated in the prefrontal cortex when compared with pups born to saline-treated dams. These results suggest that maternal LPS may have differential effects on the neuroimmune function in different regions of the offspring brain, and highlight the importance of maternal milieu in the development of neuroimmune function in the offspring.展开更多
基金supported by the National Basic Research Development Program of China (2016YFC1307100)the Shanghai Mental Health Centre Clinical Research Center Special Project for Big Data Analysis (CRC2018DSJ01-1)+2 种基金the Sanming Project of Medicine in Shenzhen City (SZSM201612006)the National Natural Science Foundation of China (91232719 and 81771465)the National Key Clinical Disciplines at Shanghai Mental Health Centre (OMA-MH, 2011-873)
文摘Neuroimmune system may be involved in the pathological process of bipolar disorder(BD),but the essential association is not fully understood.Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system(CNS).Meanwhile,neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized,such as neurotransmitter systems,neuroendocrine systems,neurotrophic factors,and oxidative stress.Simultaneously,related genes and immune changes in peripheral blood vary with it.Overall,neuroimmunity may play an important role in the pathogenesis of BD,and the inflammatory cytokines,especially interleukin-6 and tumor necrosis factor-alpha,have potential value for the clinical diagnosis and prognosis of BD,as well as predicting the therapeutic effects of drugs.Large-scale studies are needed to extend the evidence on neuroimmunity in BD,and to examine its clinical value for applications such as early prediction and treatment.
基金supported by the Foundation of Astronaut Research and Training Center of China [No.SMFA14B06 and No.14ZS017]
文摘Pulsed microwaves are widely used inradar,navigation, and communication. The average power density is low at narrow pulse widths or large pulse intervals,but pulsed microwaves at certain peak densities exert numerous biological effects, including
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
文摘AIM:To analyze visual dysfunction in rats under simulated weightlessness(SW)by examining trans-laminar cribrosa pressure difference(TLCPD)and neuroimmune responses.METHODS:The 72 male Sprague-Dawley rats were randomly assigned into two groups(ground control and hindlimb unloading-simulated microgravity)using stratified randomization,with each group further subdivided into three exposure durations:SW 2-week(SW-2W),4-week(SW-4W),and 8-week(SW-8W),n=12 per subgroup.At the designated time points for each group,intraocular pressure(IOP)and intracranial pressure(ICP)were measured,and the trans-laminar cribrosa pressure difference(TLCPD)was calculated.Additionally,optomotor response(OMR),electroretinography(ERG),and optical coherence tomography(OCT)were performed.The number of retinal ganglion cells(RGCs)was quantified via immunofluorescence,the activation of astrocytes and microglial cells was determined,and Sholl analysis was conducted to assess the function and morphology of microglial cells.Data were analyzed with SPSS and GraphPad Prism(P<0.05).RESULTS:Under prolonged simulated microgravity,rats exhibited a progressive increase in both IOP and ICP,with the most pronounced rise observed at 8wk.Concurrently,the TLCPD shifted from a negative value in controls to a positive value.These pressure alterations were associated with retinal dysfunction,as evidenced by significant reductions in ERG b-wave and photopic negative response(PhNR)amplitudes.OCT and histological analyses revealed subtle photoreceptor layer damage:while the inner nuclear layer(INL)thickness remained relatively unchanged,the outer nuclear layer(ONL)thinned significantly,and the nerve fiber layer-ganglion cell layer complex thickness(NFL-GCL)complex initially thickened before later thinning.Immunofluorescence further demonstrated marked neuroimmune activation,with astrocytes transitioning from having large cell bodies with small,elongated,sparse processes to a phenotype characterized by compact,enlarged nuclei and aggregated processes,alongside notable RGC loss.CONCLUSION:Based on the results from the simulated microgravity rat model,microgravity-induced changes in dual-chamber pressure,and neuroimmune responses in the retina may play a key role in visual dysfunction.Specifically,the activation of retinal neuroimmune cells(astrocytes and microglial cells)induced by mechanical stress appears to be central to retinal and optic nerve damage.
文摘The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.
文摘Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs frequently coexist with liver diseases,including cirrhosis,thereby exacerbating clinical manifestations and complicating management;this overlap is underpinned by shared mechanisms,including gut dysbiosis,increased intestinal permeability,systemic inflammation,and altered neuroimmune signaling.Portal hypertension in cirrhosis promotes small intestinal bacterial overgrowth and microbial translocation,thereby triggering inflammatory pathways that worsen gut and liver function.This minireview explores the gut-liver axis as a central mediator in the interplay between DGBIs and liver disease/cirrhosis.Clinically,these interactions manifest as refractory gastrointestinal symptoms,nutritional deficiencies,and impaired quality of life.Emerging research emphasizes the need for integrative diagnostic approaches,such as combining advanced imaging,microbiome analysis,and biomarker profiling,to unravel the complex interplay between DGBIs and liver disease/cirrhosis.Therapeutic interventions targeting the gut microbiome,neuroimmune pathways,and lifestyle modification can mitigate disease burden.This review underscores the importance of a multidisciplinary framework for enhancing patient outcomes and guiding future research in this intersectional field.
基金Supported by CONAHCYT Project,No.CF-2023-I-2663Instituto Nacional de Psiquiatría Project,No.NC24208.0(to Pérez-Sánchez G,Pavón L,Sánchez-Huerta K,Maldonado-García JL,Chin-Chan JM,Ponce-Regalado MD,Arreola R,Contis-Montes de Oca A,and Moreno-Lafont MC).
文摘Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.
文摘Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
基金supported by the Congressionally Directed Medical Research Program Award through the Gulf War Illness Research Program (SAR, W81XWH-21±1-0477)funding from the Aviles-Johnson Doctoral Diversity Fellowship Awardthe National Defense Science and Engineering Graduate Fellowship Awards (CAC)
文摘Gulf War Illness(GWI)is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms.Among these gastrointestinal symptoms,motility disorders are highly prevalent,presenting as chronic constipation,stomach pain,indigestion,diarrhea,and other conditions that severely impact the quality of life of GWI veterans.However,despite a high prevalence of gastrointestinal impairments among these veterans,most research attention has focused on neurological disturbances.This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI.Generally,these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI.Additionally,this perspective highlights the potential and challenges of in vitro bioengineering models,which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.
基金supported by the National Key Research and Development Project of Stem Cell and Translational Research by the Ministry of Science and Technology(2020YFA0113100)Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20211901)+1 种基金the National Natural Science Foundation of China(82071341)the Key Projects of Basic Research of Shanghai Municipal Science and Technology Commission(20JC1412000).
文摘Neuroimmune disorders,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,and Guillain–Barrésyndrome,are characterized by the dysfunction of both the immune system and the nervous system.Increasing evidence suggests that extracellular vesicles and autophagy are closely associated with the pathogenesis of these disorders.In this review,we summarize the current understanding of the interactions between extracellular vesicles and autophagy in neuroimmune disorders and discuss their potential diagnostic and therapeutic applications.Here we highlight the need for further research to fully understand the mechanisms underlying these disorders,and to develop new diagnostic and therapeutic strategies.
文摘The investigative evidence and emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many of the functional gastrointestinal disorders. Neurogastroenterological research aims for improved understanding of the physiology and pathophysiology of the digestive subsystems from which the arrays of functional symptoms emerge. The key subsystems for defecation-related symptoms and visceral hyper- sensitivity are the intestinal secretory glands, the musculature and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts for the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication and the brain-gut axis.
文摘Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory functionand pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit comorbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI
基金supported by grants from the Natural Sciences and Engineering Research Council of Canada and the Jack Brown and Family Alzheimer's Disease Research Foundation。
文摘Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis,but they also contribute to various neurological disorders,including neurotrauma,stroke,and demyelinating or neurodegenerative diseases.Immune mechanisms in the central nervous system and periphery are regulated by a diverse group of endogenous proteins,which can be broadly divided into the pro-inflammatory damageassociated molecular patterns(DAMPs)and anti-inflammatory resolution-associated molecular patterns(RAMPs),even though there is notable overlap between the DAMPand RAMP-like activities for some of these molecules.Both groups of molecular patterns were initially described in peripheral immune processes and pathologies;however,it is now evident that at least some,if not all,of these immunomodulators also regulate neuroimmune processes and contribute to neuroinflammation in diverse central nervous system disorders.The review of recent literature demonstrates that studies on DAMPs and RAMPs of the central nervous system still lag behind the much broader research effort focused on their peripheral counterparts.Nevertheless,this review also reveals that over the last five years,significant advances have been made in our understanding of the neuroimmune functions of several well-established DAMPs,including high-mobility group box 1 protein and interleukin 33.Novel neuroimmune functions have been demonstrated for other DAMPs that previously were considered almost exclusively as peripheral immune regulators;they include mitochondrial transcription factor A and cytochrome C.RAMPs of the central nervous system are an emerging area of neuroimmunology with very high translational potential since some of these molecules have already been used in preclinical and clinical studies as candidate therapeutic agents for inflammatory conditions,such as multiple sclerosis and rheumatoid arthritis.The therapeutic potential of DAMP antagonists and neutralizing antibodies in central nervous system neuroinflammatory diseases is also supported by several of the identified studies.It can be concluded that further studies of DAMPs and RAMPs of the central nervous system will continue to be an important and productive field of neuroimmunology.
基金the National Natural Science Foundation of China,No. 30901057,30871840,31072100Graduate Innovation Fund of Jilin University,No.20101057
文摘The aim of this study was to examine the immunomodulatory role of the unilateral ambiguous nucleus （Amb）. We performed electrical stimulation of the unilateral Amb, electrical stimulation of the left parietal cortex and the lateral hypothalamus following unilateral Arab lesion, as well as microinjection of acetylcholine chloride and hemicholine-3 into the unilateral Amb, and electrical stimulation of the unilateral Amb after injection of atropine, mecamylamine, propranolol, and phentolamine. Results showed that the number and proliferation of peripheral blood T lymphocytes were increased after electrical stimulation of the unilateral Arab. The cholinergic neurons in the Amb released choline substances to alter cellular immunity, thus confirming that the Amb mediates the neuro-immunomodulatory process.
基金supported by the National Natural Science Foundation of China,Nos.81671387(to YNQ),81701375(to HQD)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China.
文摘Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the interaction between the nervous and immune systems.As first responders to stress,mast cells can initiate,amplify and prolong neuroimmune responses upon activation.Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells.Corticotropin-releasing hormone can stimulate mast cell activation,influence the activation of immune cells by peripheral nerves and modulate neuroimmune interactions.The latest evidence shows that the release of corticotropin-releasing hormone induces the degranulation of mast cells under stress conditions,leading to disruption of the bloodbrain barrier,which plays an important role in neurological diseases,such as Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,autism spectrum disorder and amyotrophic lateral sclerosis.Recent studies suggest that stress increases intestinal permeability and disrupts the blood-brain barrier through corticotropin-releasing hormone-mediated activation of mast cells,providing new insight into the complex interplay between the brain and gastrointestinal tract.The neuroimmune target of mast cells is the site at which the corticotropin-releasing hormone directly participates in the inflammatory responses of nerve terminals.In this review,we focus on the neuroimmune connections between corticotropin-releasing hormone and mast cells,with the aim of providing novel potential therapeutic targets for inflammatory,autoimmune and nervous system diseases.
基金Supported by National Natural Science Foundation of China,No. 82071347 and No. 81771354 (to Dai RP)
文摘Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.
基金the National Natural Science Foundation of China(No.81570427 and No.81974039).
文摘Coronavirus disease 2019(COVID-19)has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide.Among the infected patients,there is a high prevalence of COVID-19-related cardiovascular injuries.However,the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear.The COVID-19 pandemic also has exacerbated the mental health burden of humans.Considering the close association between neuroimmune interactions and cardiovascular disease,this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease.It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage.Specifically,the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal(HPA)axis,sympathovagal imbalance,and endothelial dysfunction,which lead to an increased risk of developing cardiovascular injury during COVID-19.Therefore,during the prevention and treatment of cardiovascular complications in COVID-19 patients,particular attention should be given to relieve the mental health burden of these patients.
基金Supported by Ratchadapisek Research Funds,Faculty of Medicine,Chulalongkorn University,No.RA60/042(to BK),and No.RA61/050(to MM).
文摘BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.
文摘Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activation on the offspring’s neuroimmune function. The offspring born to dams treated with saline or lipopolysaccharide (LPS) at gestational day 18 was stimulated with saline or LPS at postnatal day 21, and the mRNA expression of various inflammatory genes in different brain regions of the offspring was analyzed. The offspring born to saline-treated dams exhibited a typical neuroimmune response with elevated levels of cytokines and chemokines following LPS stimulation in all four brain regions examined. In contrast, the offspring born to LPS- treated dams exhibited significantly reduced mRNA induction of cytokines and chemokines following LPS stimulation in the prefrontal cortex but not in the brainstem when compared with pups born to saline-treated dams. Furthermore, the mRNA expression of LPS-induced I-κBζ was significantly attenuated in the prefrontal cortex when compared with pups born to saline-treated dams. These results suggest that maternal LPS may have differential effects on the neuroimmune function in different regions of the offspring brain, and highlight the importance of maternal milieu in the development of neuroimmune function in the offspring.
