Using microglia-derived extracellular vesicles to capture diversity of microglial activation phenotypes following neurological injury

Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.

Could mammalian inorganic polyphosphate be a crucial signaling molecule in neurological disorders?

Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highest levels of metabolic complexity,have developed an elegant system that uses constant and rechargeable energy sources of modulate their metabolism.This homeostasis is especially important in the central nervous system,as neurons and other cells in the brain are highly susceptible to fluctuations in nutrients and oxygen availability.

Neuroprotective potential of traditional Ayurvedic Kadha:age-related neurological disorders:a comprehensive literature review

Despite modern medicine’s advancements,age-related neurological diseases like Alzheimer’s disease and Parkinson’s disease remain challenging due to high costs,side effects,and limited accessibility.Ayurveda,a traditional Indian medicine system,offers Kadha tea as a potential herbal option.This review explores Kadha’s components(basil(Ocimum basilicum L.),black pepper(Piper nigrum L.),Cinnamon(Cinnamomum verum J.Presl),ginger(Zingiber officinale Roscoe),and raisin(Vitis vinifera L.))and their interaction with various neurological disorders.Studies suggest Kadha exhibits anti-inflammatory,antioxidant,and antiviral properties,potentially impacting Alzheimer’s disease,Parkinson’s disease,neurotoxicity,neuroinflammation,and brain trauma.By focusing on specific disease mechanisms and Kadha’s intergrade effects,this review aims to elucidate its potential role in managing age-related neurological disorders.

Neurological Manifestations of Vitamin B12 Deficiency: About a Case

The authors report a case of deficient sensory neuropathy secondary to vitamin B12 deficiency, diagnosed in the neurology department of the Sino-Central African Friendship University Hospital in Bangui. The diagnosis was made possible by electroneuromyography which showed subclinical neurological damage associated with hematological damage (anemia). Through this observation, we recall the diagnostic criteria of the disease in a context of difficult medical practice. .

Steel bar penetrating cervical spinal canal without neurological injury:A case report

BACKGROUND We report a rare case of cervical spinal canal penetrating trauma and review the relevant literatures.CASE SUMMARY A 58-year-old male patient was admitted to the emergency department with a steel bar penetrating the neck,without signs of neurological deficit.Computed tomography(CT)demonstrated that the steel bar had penetrated the cervical spinal canal at the C6–7 level,causing C6 and C7 vertebral body fracture,C6 left lamina fracture,left facet joint fracture,and penetration of the cervical spinal cord.The steel bar was successfully removed through an open surgical procedure by a multidisciplinary team.During the surgery,we found that the cervical vertebra,cervical spinal canal and cervical spinal cord were all severely injured.Postoperative CT demonstrated severe penetration of the cervical spinal canal but the patient returned to a fully functional level without any neurological deficits.CONCLUSION Even with a serious cervical spinal canal penetrating trauma,the patient could resume normal work and life after appropriate treatment.

Exploiting fly models to investigate rare human neurological disorders

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.

Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

The Effect of Different Hyperbaric Oxygen Treatment Time Windows on Neurological Function and Prognosis in Acute Cerebral Infarction

Objective:To observe the effects of different hyperbaric oxygen treatment time windows on the prognosis and neurological function of acute cerebral infarction.Method:160 patients with acute cerebral infarction admitted to Xiangyang Central Hospital in Hubei Province were randomly divided into four groups,each with 40 cases,using a random number table method.According to the 2017 guidelines for the treatment of cerebral infarction,the control group received routine treatment for acute cerebral infarction;On the basis of the control group,patients in Group A received hyperbaric oxygen therapy within 48 hours of onset;Group B patients receive hyperbaric oxygen therapy within 3-6 days of onset;Group C patients receive hyperbaric oxygen therapy within 7-12 days of onset.Observe the efficacy,recurrence,and neurological function recovery of four groups of patients after treatment.Result:There was no statistically significant difference in the National Institutes of Health Stroke Scale(NIHSS)and Barthel Index(BI)scores among the four groups before treatment(P>0.05).There were statistically significant differences in NIHSS and BI scores between 14 and 30 days after treatment and before treatment(F=16.352,27.261,11.899,28.326,P<0.05).At 14 and 30 days after treatment,the NIHSS score in Group A decreased compared to the control group,Group B,and Group C,while the BI score increased compared to the control group,Group B,and Group C,with statistical significance(P<0.05).There was no statistically significant difference in NIHSS and BI scores between Group C and the control group after treatment(P>0.05).After 30 days of treatment,the total effective rate of Group A was higher than that of the control group and Group C,and the difference was statistically significant(X2=6.135,P<0.05).The one-year recurrence rate of Group A and Group B is lower than that of Group C and the control group,and the difference is statistically significant(X2=8.331,P<0.05).There was no statistically significant difference in adverse reactions among the four groups(P>0.05).Conclusion:Patients with acute cerebral infarction who receive hyperbaric oxygen therapy within 48 hours can improve neurological function and reduce the recurrence rate.The efficacy of receiving hyperbaric oxygen therapy within 7-12 days of onset is equivalent to that of not receiving hyperbaric oxygen therapy.

Neuro faces of beneficial T cells:essential in brain,impaired in aging and neurological diseases,and activated functionally by neurotransmitters and neuropeptides

T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.

Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins

Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood.In this study,we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS.To help determine the mechanism of action,we measured levels of seve ral impo rtant brain activity-related proteins and their mRNA.On the injured side of the brain,we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor,tropomyosin receptor kinase B,N-methyl-D-aspartic acid receptor 1,and phosphorylated cAMP response element binding protein,which are closely associated with the occurrence of long-term potentiation.rTMS also partially reve rsed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure.These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.

Repurposing niclosamide for the treatment of neurological disorders

Neurological disorders are still one of the major causes of death,and the vast need to find efficacious therapy is nowadays an essential goal of the scientific community.For Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),spinal cord injury,and intracerebral hemorrhage.

Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury

Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.

Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases

Since dental pulp stem cells(DPSCs)were first reported,six types of dental SCs(DSCs)have been isolated and identified.DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuroectodermal features.As a member of DSCs,dental follicle SCs(DFSCs)are the only cell type obtained at the early developing stage of the tooth prior to eruption.Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues,which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications.Furthermore,DFSCs exhibit a significantly higher cell proliferation rate,higher colony-formation capacity,and more primitive and better anti-inflammatory effects than other DSCs.In this respect,DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases,with natural advantages based on their origin.Lastly,cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications.This review summarizes and comments on the properties,application potential,and clinical transformation value of DFSCs,thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.

Influence of ganglioside combined with methylprednisolone sodium succinate on efficacy and neurological function in patients with acute myelitis

BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.

Drug utilization evaluation of medications used in the management of neurological disorders

Background and object:The burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition,with irrational drug use,which is also a global concern.Thus,drug utilization evaluation is designed to ensure appropriate medicine use within the healthcare settings.The aim of the study was to assess the rate and pattern of drug utilization in the management of neurological disorders.Materials and methods:A hospital-based cross-sectional drug utilization evaluation study on neurological drugs was carried out at the Department of Neurology over a span of six months.All legible prescriptions consisting neurological medications irrespective of patient's gender,aged≥18 years were included for the study.The World Health Organization(WHO)core drug use indicators were used to assess the drug prescribing and utilization patterns.Results:A total of 310 prescriptions were reviewed,where male predominance was found to be 56.45%.Out of 310 prescriptions,drugs belonging to 26 neurological classes were prescribed for the management of various neurological disorders.The majority of patients were diagnosed with epilepsy and the most prescribed drugs per patient were phenytoin(14.8%)and valproic acid(6.45%).By following the WHO core drug prescribing indicators,65.47%of drugs prescribed from the India National List of Essential Medicines,2022,followed by 29.83%of drugs prescribed in generic name and 10.86%of prescriptions including injections.Conclusion:The study findings showed that the prescribing pattern in the Department of Neurology was in accordance with the WHO core prescribing indicators.But,the extent of polypharmacy prescriptions was very high.Therefore,interventions are very necessary to promote rational drug prescribing patterns and thus clinical pharmacists can contribute to assess and review the drug utilization pattern to optimize the drug therapy and improvement in patient safety.

Past,present,and future of deep transcranial magnetic stimulation:A review in psychiatric and neurological disorders

Deep transcranial magnetic stimulation(DTMS)is a new non-invasive neuromodulation technique based on repetitive transcranial magnetic stimulation technology.The new H-coil has significant advantages in the treatment and mechanism research of psychiatric and neurological disorders.This is due to its deep stimulation site and wide range of action.This paper reviews the clinical progress of DTMS in psychiatric and neurological disorders such as Parkinson’s disease,Alzheimer’s disease,post-stroke motor dysfunction,aphasia,and other neurological disorders,as well as anxiety,depression,and schizophrenia.

miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

The ferroptosis activity is associated with neurological recovery following chronic compressive spinal cord injury

Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium state of neurological dysfunction.Ferroptosis is a crucial pathological process in many neurodegenerative diseases;however,its role in chro nic compressive spinal cord injury remains unclear.In this study,we established a chronic compressive spinal cord injury rat model,which displayed its most severe behavioral and electrophysiological dysfunction at 4 wee ks and partial recovery at 8 weeks after compression.Bulk RNA sequencing data identified enriched functional pathways,including ferroptosis,presynapse,and postsynaptic membrane activity at both 4 and 8 wee ks following chro nic compressive spinal co rd injury.Tra nsmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression.Ferro ptosis activity was negatively correlated with behavioral score.Immunofluorescence,quantitative polymerase chain reaction,and western blotting showed that expression of the anti-ferroptosis molecules,glutathione peroxidase 4(GPX4) and MAF BZIP transcription factor G(MafG),in neuro ns was suppressed at 4 weeks and upregulated at 8 weeks following spinal co rd compression.There was a positive correlation between the expression of these two molecules,suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury.In conclusion,our study determined the genome-wide expression profile and fe rroptosis activity of a consistently compressed spinal cord at different time points.The results showed that anti-fe rroptosis genes,specifically GPX4 and MafG,may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury.These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.

Synaptic alterations as a common phase in neurological and neurodevelopmental diseases: JNK is a key mediator in synaptic changes

Brain synapses play a key role in neuronal communication:this“conversation”is at the basis of all brain activities and synaptic dysfunction leads to brain disorders.We study the modulators of this crucial synaptic function and we here present the evidence supporting the c-Jun N-terminal kinase(JNK)pathway as a pivotal actor in this scenario.