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Differential roles of ERK,JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats:Multi-electrode array recordings

Differential roles of ERK,JNK and p38 MAPK in pain-related s...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Rui-Rui WANG,Ming-Gang LIU,Xue-Feng CHEN,Fu-Kang ZHANG,Xiu-Yu CUI,Jun CHEN 1 Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,The Fourth Military Medical University,Xi'an 710038,China 2 Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China

Objective It is known that chronic pain affects various higher brain functions including perception, emotion,cognition,and ***,few studies have been performed to examine pain-induced synaptic plastic changes in the hippocampal formation(HF),an important region subserving affective-motivational component of *** previous study has revealed a strong impact of peripheral persistent nociception on synaptic connection, transmission and function in the HF of rats,"in both temporal and spatial ***,the underlying signaling mechanisms for this pain-related spatial and temporal plasticity are still less *** present study attempted to examine potential different roles of the mitogen-activated protein kinase(MAPK)members in mediating this plastic *** Inhibitors targeting extracellular signal-regulated kinase(ERK),p38 MAPK and c-Jun N-terminal kinase(JNK)were used *** and temporal components of entorhinal-hippocampal synaptic connections and efficacy of rats were recorded by using a newly developed 64-channels(8x8)multielectrode array technique(Med64 system).Results(1)Pharmacological inhibition of the ERK-and JNK-mediated signaling pathway,at the plateau phase of the long-term potentiation(LTP),significantly decreased pain-enhanced LTP maintenance whereas similar blockade of p38 MAPK pathway dramatically further increased the potentiation. (2)Regarding the spatial magnification of pain,ERK and p38 MAPK seemed to play opposing roles,with the former positively involved and the latter negatively involved,without any detectable effect of the JNK signaling pathway. Conclusion Together,these results suggest differential roles of the specific members of the MAPK family in mediating pain-associated spatial and temporal plasticity in the HF,which are in good agreement with previous observations.

关键词： persistent pain hippocampal formation synaptic plasticity multi-electrode-array mitogen-activated protein kinases

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Electrophysiological effects of pharmacological block of HCN channels on pallidal neurons in normal and parkinsonian rats

Electrophysiological effects of pharmacological block of HCN...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Rong XU,Lei CHEN~* Department of Physiology,Qingdao University,Qingdao 266000,China

Objective The globus pallidus(GP)plays a significant role in motor control under both health and pathological *** studies have revealed that hyperpolarization activated cyclic-nucleotide gated(HCN) channels occupies a critical position in GP pacemaking *** studies have shown the expression of HCN channel in *** in vitro patch clamp recordings revealed that HCN channels are involved in the regulation of the spontaneous firing of *** present study is to investigate the in vivo effects of HCN channels in the GP under normal and parkinsionian *** In vivo extracellular recordings were performed in the present ***(1)In normal rats,micropressure ejection of 0.5 mM ZD7288,the relatively selective HCN channel antagonist,decreased the frequency of spontaneous firing from 13.9±2.6 Hz to 6.4±1.6 Hz(n=11,P<0.01)in 11 out of the 30 pallidal *** 18 out of the 30 pallidal neurons with the basal firing rate of 8.7±1.0 Hz,ZD7288 increased the firing rate to 16.5±1.8 Hz.(2)In 6-hydroxydopamine(6-OHDA)parkinsonian rats,on the lesioned side, local administration of ZD7288 decreased the firing rate from 6.1±1.6 Hz to 3.2±1.4 Hz(n=9,P<0.01)in 9 out of 20 pallidal *** another 9 pallidal neurons,ZD7288 increased the firing rate from 6.8±1.8 Hz to 15.8±3.5 Hz (n=9,P<0.01).On the unlesioned side,ZD7288 administration decreased the firing rate from 12.2±2.2 Hz to 5.8±1.6 Hz in 8 out of the 16 neurons *** 6 out of the 16 neurons,ZD7288 increased the firing rate from 7.4±2.3 Hz to 12.5±2.5 *** ZD7288-induced increase in firing rate on the lesioned side of 6-OHDA parkinsonian rats was stronger than that in normal rats(P<0.05).Conclusion The present electrophysiological findings sugguests that pharmacological block of HCN channels on pallidal neurons in normal and parkinsonian rats has different electrophysiological effects in *** may provide a rationale for further investigations into the roles of HCN channe

关键词： globus pallidus HCN channels Parkinson's disease single unit recording

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Celsr3 and Isletl positive guidepost cells in steering axonal projection

Celsr3 and Isletl positive guidepost cells in steering axona...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jia FENG,Mei-Zhi WANG,Li-Bing ZHOU~* Joint Laboratory for Brain Function and Health(BFAH),Jinan University & The university of Hong Kong,Medical School of Jinan University,Guangzhou 510632,China

Previous studies have shown that Celsr3 expression in Dlx5/6 positive cells is indispensable for internal capsule development（Zhou et al.,Science 2008）.To further study whether these cells are the same as Islet 1 positive corridor cells in the internal capsule as reported before（Lopez-Bendito et al,Cell 2006）,we inactivated Celsr3 in Isletl positive cells in the basal forebrain by crossing the double heterozygous males(Celsr3;Isletl-Cre) with homozygous Celsr3f/f females,which mice are called Celsr3|Isletl for *** Celsr3|Islet,the thalamocortical and the corticothalamic axons stopped navigation in the internal capsule at E14.5,and most fibers tangled in the ventral telencephalon but still a few axons could reach their targets,cortex and dorsal thalamus respectively at P0,which phenotype is similar,but a little subtle,to the ones in Celsr3|Dlx5/6,in which internal capsule is completely absent. This suggests expression of Celsr3 in Isletl positive cells is required for internal capsule *** we compared Isletl expression pattern between the wild type and Celsr3 from E10.5 to *** the basal forebrain, two pools of cells showed strong Isletl expression,one in the thalamic eminence and another in the internal capsule, where the thalamocortical and corticothalmic axons ***,Isletl positive cells showed much less in the mutant from E13.5,but no difference at the earlier *** the later stages,the positive cells formed a tumor-like pump in the internal capsule,where projecting axons stopped in Celsr3|Isletl *** immunostaining showed neurofilament-positvie fibers closely intermingled with Isletl-positive cells in the thalamic eminence and internal capsule from the control and Celsr3 embryos at E13.5 and *** results indicate that the growing axons probably interact with Isletl-positive guidepost cells through Celsr3 expression in these cells,which subsequently steer axons projection,and the Islet-positive guidepost cells

关键词： Celsr3 and Isletl positive guidepost cells in steering axonal projection

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Inflammatory pain induced ProBDNF and its receptors expression change in rat spinal dorsal horn

Inflammatory pain induced ProBDNF and its receptors expressi...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Hua LI~(1,2),Yang XU~1,Wen-Yu CAO~1,Xiao-Ling ZHONG~1,Yan-Wei LUO~1,Xue-Gang LUO~1,Chang-Qi LI~(1,*) 1 Department of Anatomy and Neurobiology,Xiangya School of Medicine,Central South University,Changsha 410013 2 Department of Histology and Embryology,Hunan University of Chinese Medicine,Changsha 410208

Objective To explore expression changes of ProBDNF and its receptors P75 and Sortilin in Posterior horn of the spinal cord followed by Complete Freund's Adjuvant（CFA） induced inflammatory *** Rats received plantar subcutaneous injection of CFA and saline mixed solvent 100μl,establishing inflammatory pain *** were randomly divided into normal group,after injection of CFA 6 h,1 d,3 d,7 d and 14 d *** change of paw withdrawal threshold（PWT） was observed by Von Frey fibers in rats at different time points;the expressions of ProBDNF,P75 and Sortilin in spinal dorsal hom were detected using *** PWT decreased quickly at 1 h after CFA injection,and to the lowest value at 6 *** gradually rose at 3 d and was still lower than baseline at 14 *** expression can be seen in the normal spinal dorsal *** with the contralateral side,ProBDNF was significantly increased in ispilateral spinal dorsal horn at 1d after CFA injection;the increase continued until about 7 d,and gradually restored at 14 *** rat spinal dorsal horn had a weak expression of P75,mainly in the posterior hornⅠ,Ⅱlamellar;P75 was significantly increased in the spinal dorsal horn of the injected side at 6h after CFA injection,positive products inⅢ-Ⅴlayers were also *** increase reached its peak at 7 d and gradually decreased at 14 *** positive product was weak in the normal superficial spinal dorsal *** expression in the spinal dorsal horn had no significant difference at different time points after CFA *** CFA can induce inflammatory pain more than 2 weeks duration;ProBDNF and P75 upregulation in spinal dorsal horn may be related to peripheral pain signal transmission and central sensitization in inflammatory pain.

关键词： inflammatory pain spinal dorsal horn ProBDNF P75NTR sortilin rat

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Thyrotropin-releasing hormone excited preganglionic inspiratory tracheal vagal motoneurones via multiple mechanisms

Thyrotropin-releasing hormone excited preganglionic inspirat...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Li-Li HOU~(1,2),Xu-Jiao ZHOU~1,Yong-Hua CHEN~1,Dong-Ying QIU~(1,3),Lei ZHU~2,Ji-Jiang WANG~(1,*) 1 The State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences,Fudan University Shanghai Medical College,138-Yi-Xue-Yuan Road,Shanghai 200032,China 2 Department of Respiratory Medicine,Fudan University Zhongshan Hospital,180 Fenglin Road,Shanghai 200032,China.3 Department of Gerontology,Fudan University Zhongshan Hospital,180 Fenglin Road,Shanghai 200032,China

The inspiratorily activated preganglionic tracheobronchial vagal motoneurones（I-TVMs） in the nucleus ambiguus,which predominate in the central control of the tracheobronchial smooth muscles,receive dense inputs from terminals containing thyrotropin-releasing hormone（TRH）.TRH microinjection into the nucleus ambiguus caused constriction of the tracheal smooth muscles however the neuronal and synaptic mechanisms are *** this study, the I-TVMs were retrogradedly labeled from the extrathoracic trachea of newborn rats,identified in rhythmically firing brainstem slices,and the effects of TRH were examined using *** voltage clamp TRH(100 nmol L) caused a slow excitatory inward current,enhanced the excitatory inputs and evoked a distinct oscillatory pattern of the baseline *** slow excitatory inward current and the oscillatory pattern were unaffected by blockade of chemical *** junction blocker carbenoxolone(100μmol L) prevented the oscillatory pattern without affecting the slow excitatory inward current and the enhancement of the excitatory ***(1μmol L),a blocker of both the voltage-dependent sodium transient and persistent sodium current,riluzole(20μmol L),a blocker of the persistent the sodium current,and cadmium chloride(200μmol L),a non-selective blocker of the voltagedependent calcium channels,each blocked a major proportion of the slow excitatory inward current and prevented the oscillatory *** current clamp TRH caused a slow depolarization and continuous or oscillatory firing. These results demonstrate that TRH excited the I-TVMs presynaptically via enhancement of the excitatory inputs,and postsynaptically via a slow excitatory inward current and a gap junction-mediated oscillatory pattern.

关键词： thyrotropin-releasing hormone oscillation vagal neuron

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Partial epilepsy with antecedent febrile seizures plus characterized by antiepileptic drugs-induced seizure aggravation and loss of function of Nav1.1

Partial epilepsy with antecedent febrile seizures plus chara...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Wei-Ping LIAO~*,Yi-Wu SHI,Yue-Sheng LONG,Yang ZENG,Tao SU,Na HE,Bing-Mei LI,Xiao-Rong LIU, Yong-Hong YI Institute of Neuroscience and the Second Affiliated Hospital,Guangzhou Medical College,Guangzhou 510260,China

Objective Generalized epilepsy with febrile seizures plus(GEFS+)and severe myoclonic epilepsy in infancy(SMEI)are associated with sodium channel a-subunit type-1 gene(SCNIA)mutations,although previous studies failed to correlate the functional defects(funotypes)with *** seizures and partial epilepsy are the two common features of GEFS+ and *** is thus suspected that partial epilepsy with antecedent febrile seizures(PEFS+)may also be a phenotype of SCNIA *** aggravation induced by antiepileptic drugs(AEDs),a feature of SMEI,is considered here as a clue to find SCNIA mutations in isolated PEFS+ patients. Methods Two isolated PEFS+ patients with AEDs-induced seizure aggravation were screened for mutations in SCNIA,SCN2A,SCN1B,and GABRG2 using denaturing high-performance liquid chromatography and direct *** biophysiological features of two newly defined mutants were studied in transfected tsA201 cells using whole-cell patch-clamp *** characterize PEFS+ biologically,the genotype-funotype-phenotype relationships in all previously reported SCNIA mutations were *** One PEFS+ patient each had heterozygous de novo mutations of c.2837G>A/p.R946H and c.5295 T>A/p.F1765L in SCNIA,which cause the loss of function of the *** the defining of PEFS+,classifying the funotype in detail,and considering the subtle differences in the amino acid substitution,a close genotype-funotype-phenotype relationship was found in epilepsies with SCNIA mutations at a submolecular ***+ is clinically mild,with also mild channel dysfunction and mutations outside the pore ***+ is clinically similar to GEFS+,but distinct from GEFS+ in its funotype and AEDs-induced seizure ***+ is much milder than SMEI clinically,similar to SMEI biophysiologically with features of loss of function but less in degree,structurally different from SMEI by substitutions without changes in polarity. Conclusions PEFS+ may be

关键词： SCN1A channelopathy partial epilepsy febrile seizures sodium channel

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Effects of melatonin on nigrostriatal dopamine pathway of unilateral 6-hydroxydopamine-lesioned rats

Effects of melatonin on nigrostriatal dopamine pathway of un...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Tao MENG~1,Ling LIN~(1,2,*),Zhi-Hong ZHENG~(1,2),Ting-Ting LIU~1,Zhong-Hai LIU~1,Wen-Ling XIONG~1,Mei-E YU~1, Teng-Fei GUO~1 1 Department of Biochemistry and Molecular Biology,Fujian Medical University,Fuzhou 350004,China 2 Research Center of Neurobiology,Fujian Medical University,Fuzhou 350004,China

Objective There is increasing interest in interactions between the nigrostriatal dopamine(NSD) system and the circadian system in Parkinson's *** two systems are mainly involved in neurotransmitters such as dopamine(DA) and melatonin(MLT).The purpose of our study was to investigate interactions between DA and MLT in the lesioned and intact NSD pathway of unilateral 6-hydroxydopamine(6-OHDA)-lesioned model *** Extracellular levels of DA and its metabolites DOPAC and HVA,as well as MLT in the lesioned-side striatum of unilateral 6-OHDA-lesioned rats were dynamically measured by microdialysis with *** contents of these neurotransmitters in lesioned and intact sides of midbrain and striatum,as well as pineal gland of model rats were assayed by HPLC at different times ***(1) Extracellular DA,DOPAC and HVA levels in the lesioned-side striatum of 6-OHDA-lesioned rats declined evidently,while MLT levels in the lesioned side increased distinctly at 10:00 and 22:00 compared with the controls.(2) Homogenate contents of DA,DOPAC and HVA in the lesioned-side midbrain and striatum of model rats decreased sharply,while DA,DOPAC and HVA contents in the intact side had no significant changes compared with the *** contents of MLT at 10:00 and 22:00 in both sides of midbrain and striatum,as well as pineal gland of model rats increased obviously contrast to the controls, and MLT contents in the lesioned side increased distinctly contrast to the intact *** These data suggest that MLT might play different roles in the lesioned and intact NSD pathway of unilateral 6-OHDA-lesioned *** levels of MLT may not protect dopaminergic neurons from oxidative stress in the lesioned NSD pathway of 6-OHDAlesioned rats and may even decrease the release of DA,while relative high levels of MLT may still exert antioxidant effect on the intact NSD pathway.

关键词： Parkinson's disease dopamine melatonin brain microdialysis

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Tri-lithium pyrroloquinoline quinine ameliorates cognitive impairment and extenuates cerebral pathological lesions in amyloid precursor protein/presenilin-1 transgenic mice

Tri-lithium pyrroloquinoline quinine ameliorates cognitive i...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Lei ZHAO~1,Neng GONG~2,Zhe YU~2,Qi FANG~2,Tian-Le XU~(2,*),Chun-Jiu ZHONG~(1,*) 1 Department of Neurology,Zhongshan Hospital,Fudan Univeristy,Shanghai 200032,China 2 Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

Alzheimer's disease（AD） is the most common age-related neurodegenerative disorder and cause of dementia in the elderly,characterized by global cognitive impairment and the presence of extracellular beta-amyloid （Aβ） deposition（senile plaques） and intracellular hyperphosphorylated tau protein（neurofibrillary tangles）.Currently, the dominant theory to explain pathogenesis of AD is the "Amyloid Cascade Hypothesis" first proposed in 1992. However,almost all previous clinical trials targeting Aβhave received negative *** disappointing fact triggers us to reconsider this hypothesis and to explore more effective treatment *** drastic disturbance of glucose metabolism in the brain is one of the striking features of AD.A significant reduction in cerebral glucose consumption precedes overt clinical symptoms or brain atrophy,even for *** studies have demonstrated multiple defects in glucose and energy metabolism in AD ***,the decreased glucose and energy metabolism induces various pathogeneses similar to AD such as oxidative stress,activated glucose synthase kinase-3（GSK-3） signal pathway,and excitatory and inhibitory signaling dysfunction,and so ***,the drug or therapy only targeting to a single mechanism is difficult to modify the *** is essential to design new treatment strategy that can rectify the disturbed cellular energy metabolism and stop the multiple pathogenic cascades ***,a GSK- 3 inhibitor,has been demonstrated the beneficial effect on *** quinone,a new B vitamin,has been demonstrated neuroprotective action through the mechanisms of powerful anti-oxidation and improving mitochondria *** independently synthesized tri-lithium pyrroloquinoline quinone（LiPQQ）.We found that LiPQQ exhibited a very low acute toxicity（LiPQQ ID50 2.50 g/kg weight vs LiC1 ID50 0.53 g/kg weight） by evaluating acute toxicity with *** use the amyloid precursor protein/presenilin-1（APP/PSl）

关键词： lithium pyrroloquinoline quinine Alzheimer's disease

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Cannabinoid receptor-2 contribute to the regulation of electroacupuncture on expression of β-endorphin in inflamed skin tissue of rats

Cannabinoid receptor-2 contribute to the regulation of elect...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Tang-Feng SU,Ling-Hong ZHANG,Cai-Hua WU,Yi-Qing ZHAO,Miao PENG,Bo TIAN,Jing SHI,Man LI~* Department of Neurobiology,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China

Objective It has been reported that EA-produced analgesia is mediated by endogenous opioid systems in uninjured and inflammatory pain animal ***,whether CB2Rs activation contributes to 2Hz EA regulation ofβ-endorphin in inflamed skin tissue of rats was still *** we determined the effects of CB2R activation and EA on the expression and distribution patterns of B-endorphin in inflamed skin tissues and the role of peripheral MORs in the analgesia *** Inflammatory pain was induced by injection of complete Freund's adjuvant into the left hindpaw of *** hyperalgesia was tested with a radiant heat stimulus,and mechanical allodynia was quantified using von Frey *** mRNA level of POMC and protein level of B-endorphin were quantified by using real-time PCR and Western blotting,*** distribution of B-endorphin on keratinocytes and immune cells recruited to the inflamed skin tissues was detected by using double-immunofluorescence labeling. Results(1) The CB2R agonist AM1241 and 2 Hz EA applied to GB30 and GB34 significantly reduced thermal hyperalgesia and mechanical allodynia induced by CFA *** specific CB2R antagonist AM630 and selective MOR antagonistβ-funaltrexamine significantly attenuated the antinociceptive effect 2Hz EA.(2) AM1241 and 2Hz EA significantly increased the mRNA level of POMC and protein level of B-endorphin in inflamed skin tissues. Pretreatment with AM630 significantly reversed the excitatory effect of EA onβ-endorphin expression.(3)Through activation of CB2Rs,AM1241 and 2Hz EA significantly increased the number of keratinocytes,macrophages,and T-lymphocytes withβ-endorphin-immunoreactivity in the inflamed skin *** EA primarily potentiates the expression ofβ-endorphin on keratinocytes and infiltrating inflammatory cells at the site of inflammation through activation of CB2Rs.β-endorphin in turn activates peripheral MORs to reduce inflammatory pain.

关键词： electroacupuncture hyperalgesia allodynia inflammatory pain P-endorphin cannabinoid CB2 receptors

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Antisense-mediated knockdown of Nav1.8,but not Nav1.9,generates inhibitory effects on complete Freund's adjuvant-induced inflammatory pain in rat

Antisense-mediated knockdown of Nav1.8,but not Nav1.9,genera...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yao-Qing YU~1,Feng ZHAO~1,Su-Min GUAN~2,Jun CHEN~(1,3,*) 1 Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,the Fourth Military Medical University,Xi'an 710038,China 2 School of Stomatology,the Fourth Military Medical University,Xi'an 710032,China 3 Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China

Objective:Tetrodotoxin-resistant（TTX-R） sodium channels Na1.8 and Na1.9 in sensory neurons were key pain *** with the well reported roles of Na1.8,evaluations of Na1.9 on inflammatory pain is poorly studied by antisense agents inducing specific gene ***,we used molecular,electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide（AS ODN） targeting Na1.8 and Na1.9 on inflammatory *** Complete Freund's adjuvant（CFA） was used to induce peripheral inflammatory ***-PCR,Western blot,immunocytochemistry and whole cell patch-clamp were used to evaluate the expressions and functions of Na1.8 and *** Following CFA inflammation treatment,Na1.8 and Na1.9 in rat dorsal root ganglion（DRG） were activated demonstrated in the up-regulations of mRNA and protein expression and increased sodium current *** data demonstrated that Na1.8 was mainly localized in medium and small-sized DRG neurons,whereas Na1.9 was only expressed in small-sized DRG ***（i.t.） delivery of AS ODN was used to down-regulate Na1.8 or Na1.9 expressions confirmed by immunohistochemistry and Western ***,behavioral tests showed that only Na1.8 AS ODN,but not Na1.9 AS ODN could reverse CFA-induced heat and mechanical *** Our data indicated that the key pain modulators Na1.8 and Na1.9 played distinct functional roles in the processing of inflammatory pain and antisense oligodeoxynucleotide-mediated blocking of Na1.8 over-expression might point toward a potential treatment strategy for certain type of pathological pain.

关键词： antisense oligodeoxynucleotide dorsal root ganglion Nav1.8 Nav1.9 inflammatory pain

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