Objective To observe the effects of low dose of veratrine on the discharges of rat hippocampus pyramidal neurons,and to elucidate its possible cytological mechanism.Methods The discharge features of hippocampus CA1 pyramidal neurons of 14-day-aged healthy Sprague-Dawley rats induced by low dose(0.3～0.8?mol/L)of veratrine were observed by slice patch-clamp technique.Presynap- tic stimulation was given to Schaffer collaterals.Presynaptic receptor inhibitors such as 6-cyano-7-nitroquinoxaline-2,3-dione(CNQX, 5?mol/L),DL-2-amino-5-phosphonopentanoic acid(AP-5,12.5?mol/L),bicuculline(Bic,10?mol/L)and tetrodotoxin(TTX,40～80nmol/L)were used to investigate the influence on veratrine-induced epilepsy andⅠ-Ⅴcurves were plotted under these conditions.Elec- trophysiological mechanism of veratrine-induced epilepsy was elucidated on the basis of these experiments,Results After a perfusion with low dose of veratrine,the pyramidal neurons were found to discharge relatively fixed-mode slow wave epileptoid bursts accompanied with hyperpolarization of membrane potential.These epileptoid bursts were not blocked by a mixture of CNQX,AP-5 and Bic,but by low dose of TTX.After a perfusion with veratrine,Ⅰ-Ⅴrelationship tended to be nonlinear and the depolarization rectification was enhanced,which were reversed by administration of low dose of TTX.The subthreshold TTX-sensitive persistent sodium current of CA1 pyramidal cells was enhanced by veratrine in a voltage-dependent manner.Conclusion Inducing slow wave epileptoid bursts,the low dose of veratrine can remarkably change the discharge features of CA1 pyramidal neurons.Such epileptoid activities were not influenced by the synaptic receptor inhibitors,and were obviously related to the persistent sodium current.

Objective To observe the effects of phenytoin and gabapentin in therapeutic dosage on low-dose veratridine-induced epileptiform discharge in rats' hippocampal CA1 neurons,and explore the involved mechanisms.Methods By means of whole-cell patch clamp technique,the epileptiform discharge model of rats' hippocampal CA1 neurons was constructed with extracellular perfusion of 0.5?mol/L veratridine,and the model should be regarded as successfully estabilshed if bursting discharge emerged within 30min perfusion.The effects of phenytoin(2.5,5,10 and 15?mol/L) and gabapentin(2.5,5 and 10?mol/L) on the epileptiform activity were observed under the voltage-clamp configuration,and the current changes for 1 hour in CA1 neurons was also observed.Results Nine-sixteen minutes after veratridine perfusion,the huge,rhythmic slow oscillation emerged,with 100～200Hz high-frequency discharge,in the hippocampal CA1 neurons,which was similar to the paroxysmal depolarization shifts(PDS),implying that the epileptiform activity was reproduced.Therapeutic dose of phenytoin blocked the veratridine-induced epileptiform activity.The bursting interval of the epileptiform activity was prolonged along with the increased phenytoin concentration,and the duration of bursting was not shortened.1h current decreased gradually in the generation of veratridine-induced epileptiform activity.Therapeutic dose of gabapentin did not block the epileptiform activity in this model.Conclusions In the epileptiform discharge model of rats' hippocampal CA1 neurons,phenytoin can block the epileptic activity in a dose-dependent manner,and the effect may be related to the inhibition of 1h currents.Gabapentin shows no influence on the epileptiform activity,and the possible mechanism may be its ineffectiveness to the persistent sodium currents,and vertridine-induced epileptiform activity does not enhance the 1h currents.

BACKGROUND: The event of paroxysmal deplorizing shift (PDS) is the cellular hallmark of brain neurons of epileptiform activities. Its development used to be considered to be related to abnormal synaptic interactions. Recertly, the intrinsic nature of PDS has received more attention.OBJECTIVE: To observe the characteristics of epileptiform activities of rat hippocampal CA1 pyramidal neurons induced by low-dosage veratridine and investigate its possible ion mechanism.DESIGN: An exploratory and observational trial.SETTING: Institute of Neuroscience, Fourth Military Medical University of Chinese PLA.MATERIALS: This study was conducted at the Institute of Neuroscience,Fourth Military Medical University of Chinese PLA, from October 2002 to October 2004. Forty healthy SD rats of 14 days old were selected. Drugs were provided from Tianjin Drug Company and Sigma Company.METHODS: Rats were anesthetized by intraperitoneal injection, and their brain was removed and cut into slices. Epileptiform activities were induced by 0.5 μ mol/L veratridine. Then 80 nmol/L tetrodotoxin was added into the perfused solution on 6 cerebral slices, and 5 μmol/L phenytoin was used on another 5 cerebral slices. The electrophysiological characteristics of the cells under the effect of different kinds of drugs were observed.MAIN OUTCOME MEASURE: Discharge pattern of cells and tetrodotoxin-sensitive sodium currents under voltage-clamp configuration through Ⅰ-Ⅴ reaction.RESULTS: After perfusion of 0.5 μmol/L veratridine, the rat pyramidal neurons in CA1 area displayed relatively fixed-mode of runs of PDS bursting,followed by the hyperpolarization of cell membrane. Such epileptiform activities were blocked either by 80 nmol/L tetrodotoxin or 5 μnol/L phenytoin. The tetrodotoxin-sensitive sodium currents in epileptic neurons and normal controls under voltage-clamp configuration on holding potential of -55 rmV, -60 rmV, -65 mV. This shows that persistent sodium currents could be improved by low-dosage veratridine in a voltage-dependent manner.CONCLUSION: Low-dosage veratridine may induce runs of PDS like epileptiform activities on rat CA1 pyramidal neurons. Such changes can be blocked by low-dosage tetrodotoxin or phenytoin. Its ion mechanism may be related to persistent sodium currents.

Objective To assess the epidemiology and clinical characteristics of sleep disorders in a single center in northwest China.Methods Using the International Classification of Sleep Disorders, 3rd Edition, all consecutive patients which were suspected as sleep disorders in Tangdu Hospital between January 2007 and December 2016, were included retrospectively.Results The average age of 8 037 patients was (46.59±15.83) years with male-female ratio 1∶1.24.Chronic insomnia was found in 3 848 (47.9%) patients, obstructive sleep apnea was found in 2 648 (32.9%) patients, narcolepsy was found in 294 (3.7%) patients, Kleine-Levin syndrome was found in 11 (0.1%) patients, circadian rhythm sleep-wake disorders were found in 14 (0.2%) patients, rapid eye movement behavior disorder was found in 193 (2.4%) patients, restless legs syndrome was found in 139 (1.7%) patients, periodic limb movement disorder was found in 109 (1.4%) patients, and other possible sleep disorders were found in 478 (5.9%) patients, respectively.Chronic insomnia and obstructive sleep apnea combided with somatic diseases.Conclusions Patients diagnosed by polysomnography in our single center suggested consultation rate of sleep disorders was increasing in past ten years, of which chronic insomnia and obstructive sleep apnea were dominant and comorbided with somatic diseases.

Objective To observe the changes of cerebral inflammation-related markers in brain of a transgenic mouse model of Alzheimer's disease (AD) ,and to determine the causative factor to the development of cerebral inflammation in AD. Methods 3- and 12-month-old β-amyloid protein precursor ( APP)/presenilin (PSI) transgenic mice and age-matched wild-type mice (WT) were used in the study. The changes of amyloid plaques, inflammatory factors ( interleukin 1β ( IL-1β ); interleukin 6( IL-6 ); tumor necrosis factor α (TNFα) ;prostaglandin E2 (PGE2)) in the brains among these mice were measured by immunohistochemistry and ELISA. Results Immunohistochemical analysis revealed that no amyloid plaques and activated astrocytes as well as microglia were observed in the 3-month-old APP/PS1 mice. There were no significant differences in the levels of inflammatory factors (IL-1β, IL-6 ,TNFα,and PGE2) between the 3-month-old APP/PS1 and WT mice ( Ps ＞ 0. 05 ). However, abundant amyloid plaques accompanied by a remarkable increase of activated astrocytes and microglia were found in the brain of the 12-month-old APP/PS1 mice. The levels of inflammatory factors (IL-1β,IL-6,TNFα, and PGE2 ) were significantly increased in the 12-month-old APP/PS1 mice ([56. 02 ±9. 04] ng/g, [8. 66 ±0.83] ng/g, [97.48 ±26.58] ng/g, [72. 18 ±21.01] ng/g) than in the WT mice ([29. 18 ± 6. 03] ng/g, [7. 73 ± 0. 74] ng/g, [61.98 ±11.11] ng/g, [37. 23 ± 10. 96] ng/g) and the 3-month-old APP/PS1 mice ( [30. 05 ± 3.53] ng/g, [7.43 ± 1.17] ng/g, [59.34 ± 10. 07] ng/g, [42. 56 ±5.93] ng/g) (P＜0.05,or P＜0.01,respectively). Conclusion This study demonstrates that the APP/PS1mice did not show cerebral inflammation before the appearance of amyloid plaques, and exhibited remarkable inflammation after amyloid plaque deposition. These findings suggest that the induction of cerebral inflammation is tightly associated with amyloid plaque formation, and deposition of amyloid-beta protein (Aβ) may be the direct causative factor to the development of cerebral inflammation in AD.

Objective To investigate the clinical features of restless legs syndrome(RLS),its possible pathogenesis.and the effects of benserazide on the patients with RLS.Methods Twenty-three patients who met the primary diagnostic criteria of RLS were retrospectively analyzed.Results Twenty-three middle-aged or elderly patients aged 56 years in average had an average onset age of 52 years.Insomnia and daytime sleepiness were mostly common complains for these patients.Based on the diagnostic criteria of International RLS study group(IRLSSG),the average IRLSSG score was 25,and 16 cases(69%)of the patients were severe(21-30).Polysomnographic examination showed that 18 cases(78%)had periodic limb movement.in which the PLM index of 11 cases(61%)patients Was moderate(25-49).PLM-arousal index of all patients was increased.that of 16 cases(67%)patients being moderate.After treatment by levodopa/benserazide 100/25 mg at bedtime each night for 4 weeks,most of patients'subjective symptoms improved markedly.and the IRLSSG score Was obviously decreased.with an average score of 13,and 5 patients became completely normal.Among patients with periodic legs movement.the PLM index became normal in 5 patients and became mild in others.In addition.the PLM-arousal index in all patients Was markedly decreased.with that of 11 patients becoming normal.The sleep latency of 19 patients became normal.On the other hand,6 patients(26%)had transient headache,nausea,and lethargy.Conclusions Patients with discomfortable feeling of lower extremity which is mitigated after movement.and legs movement during sleep should be check up as early as possible.Benserazide may be considered as an effeetive medication for patients with RLS.

Objective To investigate the clinical features and the possible pathogenesis of rhythmic movement disorder (RMD) by analyzing 2 patients with RMD and reviewing the literature. Methods By using overnight polysomnogram (PSG) and sleeping video monitoring, the movement patterns, sleep architecture, and sleep quality of 2 patients who met the RMD diagnostic criteria were examined. Results Two male patients were 15-years old. The onset age of patient 1 was 3-years old, and patient 2 was 10-years old. All abnormal movements occurred in sleep, which presented with repetitive, stereotyping and rhythmical movements. Multiple patterns of abnormal sleeping movement were observed in 2 patients: head hypsokinesis, thoracic and waist hyperextension, and pendular movement of bilateral upper extremities. In the sitting position, the patient exhibited kneeling position, and fore-and-aft or lateral rhythmical swing of the upper body accompanied with head-banging. In the prone position, the patient behaved head backward hyperextension, and horizontal and fluctuating pendular movement of the body, which was just like the auto-erotic situation. In the lateral sleep position, the patient supported their head by using the right hand accompanied with fore-and-aft pendular movement of the head and the upper body. These symptoms mentioned above emerged immediately when the patient fell asleep, and continuously existed in all sleep period including non-rapid eye movement and rapid eye movement. All of the symptoms disappeared once the patient woke. The abnormal movement frequency was 0.1-2.0 Hz. In addition, the sleep architecture and quality were severely influenced by RMD in patient 2. Clonazepam might markedly ameliorate the symptoms and sleep quality. Conclusions Multiple abnormal movement patterns may exist in the RMD patients, and these abnormal movements could last during the whole sleep period. PSG and sleeping video monitoring should be undertaken for the suspected RMD patients, which are very useful for the definite diagnosis of RMD.

Objective To explore the expression and function of galanin and its receptor in the female mice of anxiety-and depression-like behavior.Methods In situ hybridization was used to detect the expression of galanin,GalR1,GalR2 and GalR3 in the hippocampus of C57BL/6J female mice.A total of thirty female mice was divided into two groups:experiment group (n=15) and control group (n=15).The experiment group was subjected to the chronic unpredictable mild stress (CUMS) for four weeks,and the control group was not subjected to any treatment.Four weeks later,a series of tests were performed on those two groups,including the sucrose preference test,the novel object recognition test,the open field test and suspension tail test.After behavior tests,the hippocampus RNA was extracted from eight mice in each group to test the expression of galanin and its receptor through qPCR.The rest part of mice were used to mark C-Fos immunostaining in the dentate gyms (DG) of hippocampus.Results The result of in situ hybridization showed that galanin,GalR1 and GalR2 distributed in the Hillus of ventral hippocamous,GalR3 had no positive signal.In the sucrose preference test,the experiment group drunk less sucrose when compared with the control group (P＜0.05).In the novel object recognition test,the experiment group contacted shorter time to the novel object when compared with the control group (P＜0.05).In the open field test,the experiment group had shorter in session time when compared with the control group (P＜0.05).In the suspension tail test,the experiment group had longer immobility time when compared with the control group (P＜0.05).The qPCR result showed that the higher expression of galanin and GalR1 in the hippocampus of experiment group (P＜0.05).More C-Fos positive cells in the DG of hippocampus of experiment mice were immunostained (P＜0.05).Conclusions Galanin,GalR1 and GalR2 mainly distribute in the Hillus of the ventral hippocampus.Galanin may be involved in the anxiety-and depression-like behavior of C57BL/6J through GalR1.

Objective　To understand the relationship between elective motivation and sleep emotional characteristics of students in sleep medicine course.Methods　The study used Wenjuanxing to investigate data,including demographic data,motivation to elect the Sleep Medicine Course,Pittsburgh Sleep Quality Index (PSQI),Insomnia Severity Index (ISI),Epworth Sleep Score (ESS),Morningness/Eveningness Questionnaire (MEQ),Self-Rating Depression Scale (SDS),Self-Rating Anxiety Scale (SAS) and Fatigue Severity Scale (FSS).Results　From 2017 to 2019,410 students selected the Sleep Medicine Course,in which 70.3% were interested in the course and 27.4% had the demands to resolve sleep problems.The percentage of PSQI≥6 is 28.85%，ESS ≥9 is 6.15%,ISI≥8 is 29.49%,SAS≥508 is 9.1%,SDS≥53 is 25%，the score of FSS is 35.9±12.5.Students were separated to three different groups by cluster analysis.The characteristic of first group was depression (14%),the second group was anxiety and fatigue (63%),and the third was poor sleep quality,sleepiness,anxiety,fatigue,and depression (23%).Conclusions　The motivation of taking Sleep Medicine Courses may be related to the high level of anxiety.Sleep problems are prone to comorbid anxiety and depression and affect daytime function.