Effects of rapamycin intervention during pregnancy on cognitive function of autism model in rat offspring / 中国临床药理学与治疗学

AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring. METHODS: Fourteen pregnant rats were randomly divided into normal group (n = 3), model group (n = 4), rapamycin (RAPA) control group (n =3) and intervention group (n = 4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P < 0.05), while the indexes between the intervention group and model group were reversed (P < 0.05). The model group had higher PWMT than normal group (P < 0.01) and the PWMT of intervention group was lower than that of model group (P < 0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P < 0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P < 0.01) and intervention group shifted to left compared with model group (P < 0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P < 0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P < 0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.

Establishing reference intervals of serum anti-Müllerian hormone in women of childbearing age (20-34 years old) in Henan area / 中华检验医学杂志

Objective:To analyze the serum anti-Müllerian hormone (AMH) levels in women of childbearing age in different age groups in Henan, and establish the medical reference intervals based on measurement results from this population.Methods:From January to June 2017, 620 healthy women of childbearing age (20-34 years old), who underwent pre-pregnancy eugenics and pre-marital checkups in 13 project sites in Henan, were included in this study. Participants were divided into 3 age groups: 20-24 years group ( n=210), 25-29 years group ( n=207), and 30-34 years group ( n=203). Spearman correlation coefficient was used to evaluate the correlation between serum AMH level and age; Kruskal-Wallis H test was used to compare the serum AMH levels of different age groups; Wilcoxon test was used for comparison between pairs; the percentile method ( P2.5, P97.5) was used to establish medical reference interval of serum AMH in women of childbearing age for the whole population and different age groups, respectively. Results:The correlation coefficient between serum AMH and age in women of childbearing age (20-34 years old) is -0.17 ( P<0.001). There was a statistically significant difference in the overall frequency distribution of serum AMH levels among the three different age groups ( H=21.978, P<0.05). Among them, there is a statistically significant difference between the 20-24 years group and the 30-34 years group ( Z=4.292, P<0.05). There is a statistically significant difference between the 25-29 years group and the 30-34 years group ( Z=3.803, P<0.05). The reference range of serum AMH is 0.281-9.693 μg/L in this cohort; the reference range of serum AMH is 0.524-10.760, 0.229-9.200, 0.115-8.200 μg/L for women of childbearing age at 20-24, 25-29 and 30-34 years, respectively. Conclusion:The serum AMH level of women of childbearing age (20-34 years old) decreases with age. It is of great significance to establish the serum AMH reference interval for women of childbearing age in different age groups in Henan.

Etomidate reduces excitability of the neurons and suppresses the function of nAChR ventral horn in the spinal cord of neonatal rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord.@*METHODS@#The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time.@*RESULTS@#The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed ( < 0.01), and spontaneous discharge frequency was obviously reduced ( < 0.01, =12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures ( < 0.01, =6).@*CONCLUSIONS@#etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.

Electrophysiological monitoring of pain afferent pathway of the trigeminal nerve and its functional plasticity in response to occlusal interference in rats / 南方医科大学学报

OBJECTIVE@#To observe the effect of occlusal interference on the afferent pathway of the trigeminal nerve and neuronal excitability in the trigeminal subnucleus caudalis (SPVC) of rats by electrical stimulation of the trigeminal ganglion (TG) and extracellular recordings of SPVC activities.@*METHODS@#Twenty male Wistar rats were randomly divided into control group and model group (=10). In the model group, occlusal interference for 30 consecutive days was induced using light-cured flowable resin on the right maxillary molars. During occlusal interference, the pain sensitivity was scored with von Frey Fibers in the masseter. Simultaneous recordings of electrical activities from the SPVC, electrocardiogram, body temperature and electromyogram of the breath muscles of the anesthetized rats were performed, and the responses evoked by electrical stimulation of the TG were analyzed.@*RESULTS@#Compared with the control rats, the rats in the model group showed significantly increased pain sensitivity scores ( 0.05). Train stimulation (0.2 ms, 1 mA, 30 s, 100 Hz) of the TG significantly increased the discharge frequency of the SPVC only in the rats in the model group ( < 0.05).@*CONCLUSIONS@#The functional activities of the pain afferent pathway of the trigeminal nerve can be electrophysiologically monitored by electrical stimulation of the TG and extracellular recordings of SPVC activities in rats. Occlusal interference can increase the excitability of the neurons in the SPVC and enhance their sensitivities to TG afferent activation, suggesting the neural plasticity of the pain afferent pathway.

β2-nicotinic acetylcholine receptor promotes development of GABA receptors in mouse hippocampal CA1 and CA3 pyramidal neurons / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of β2-nicotinic acetylcholine receptor (β2-nAChR) in the development of γ- aminobutyric acid A type receptors (GABA-Rs) in hippocampal CA1 and CA3 pyramidal neurons of mice.</p><p><b>METHODS</b>The hippocampal CA1 and CA3 pyramidal neurons were acutely isolated from β2-nAChR gene knockout (β2-KO group) mice. GABA currents in CA1 and CA3 pyramidal neurons were induced with the selective GABA-R agonist muscimol and recorded using perforated patch-clamp recording technique. The GABA currents of CA1 and CA3 pyramidal neurons were tested for their equilibrium potentials (Es) and kinetic parameters and were compared with the measurements in wild-type mice (WT group).</p><p><b>RESULTS</b>The mean E of CA1 neurons (=7) of β2-KO mice (=4) was -31.7±3.5 mV, showing an obvious depolarizing shift compared with the WT mice ( < 0.05); the mean E of CA3 neurons (=4) was -16.1±4.6 mV, also showing a depolarizing shift ( < 0.01). The difference in the Es between CA3 and CA1 neurons in β2-KO mice, but not in WT mice, was significant ( < 0.05). The GABA-R desensitization was significantly slowed down in both CA1 and CA3 neurons of β2-KO mice, with decay time of 2.2±0.2 s and 3.2±0.1 s, respectively, significantly longer than those in WT mice (1.6±0.1 s and 2.3±0.1 s, respectively; < 0.05).</p><p><b>CONCLUSIONS</b>β2-containing nAChRs may promote the functional maturation of GABA-R in CA1 and CA3 pyramidal cells in mouse hippocampus.</p>

Characteristics of opening movement in patients with unilateral mastication / 中南大学学报(医学版)

OBJECTIVE@#To analyze characteristics of mandibular movement in patients with unilateral mastication.
@*METHODS@#Undergraduate students in oral medicine from Grade 2011 and 2012 in Wannan Medical College were enrolled for this study by cluster sampling method, which include 30 people with unilateral mastication and 30 people with bilateral mastication. The surface electromyogram (sEMG) of masseter muscle and anterovent of digastric muscle were recorded and the trajectory of mandibular incisor point was recorded simultaneously in the maximum opening and closing movement. The results were analyzed by SPSS 19.0 software.
@*RESULTS@#Average electrical peak of left anterior digastric muscle and right anterior digastric muscle in the unilateral chewing group was lower than that in the bilateral chewing group (P<0.05). The jaw tangent point trajectory was separate in the unilateral chewing group. There were significant differences at the opening type between the 2 groups. The vertical displacement and the sagittal displacement in the unilateral chewing group were significantly lower than those in the bilateral chewing group (P<0.01). There was significant positive correlation between the average peak potential of masseter muscle and displacement on the right side.
@*CONCLUSION@#Average electrical peak of left masseter muscle, left anterior digastric muscle, and right anterior digastric muscle decreases in the unilateral chewing group. Jaw tracking in most people deflects to the working side. Opening and closing jaw tracking is separate in 50% unilateral chewing individuals with the decreased opening degree. Unilateral chewing leads to changes in muscle performance accompanied by trajectory anomalies.

Effects of biological rhythm disturbance on sedation induced by propofol in rats / 中华麻醉学杂志

Objective To evaluate the effects of biological rhythm disturbance on sedation induced by propofol in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups (n =8 each) using a random number table:circadian rhythm + administration during night-time group (group CN),circadian rhythm + administration during day-time group (group CD),biological rhythm+administration during night-time group (group BN),and biological rhythm+administration during day-time group (group BD).In CN and CD groups,the rats were fed for 2 weeks in the experimental boxes in a 12 (7:00-19:00):12 h (19:00-7:00) light:dark cycle.While the rats were fed for 2 weeks in the experimental boxes in a 24 h light cycle.Propofol 75 mg/kg was intraperitoneally injected at 14:00 in CN and BN groups,or at 22:00 in CD and BD groups.The duration of loss of righting reflex was recorded.At 20 min after recovery of righting reflex,the cognitive function was assessed.The latency of passive avoidance was measured at 6,12,24 and 48 h after training.Results Compared with group CN,the duration of loss of righting reflex was significantly shortened,and the latency of passive avoidance was prolonged at 12 and 24 h after training in group CD,and the duration of loss of righting reflex and latency of passive avoidance at 12 and 24 h after training were shortened in group BN.Compared with group CD,no significant change was found in the duration of loss of righting reflex,and the latency of passive avoidance was significantly shortened at 24 h after training in group BD.There was no significant change between BN group and BD group in the duration of loss of righting reflex and latency of passive avoidance.Conclusion Biological rhythm disturbance can counteract circadian rhythmproduced effects on sedation induced by propofol in rats.

Effects of yohimbine on norepinephrine release by locus coeruleus in stressed rats / 中华行为医学与脑科学杂志

Objective To study the cellular and molecular modulation mechanisms of norepinephrine (NE) release in hypothalamus induced by electrical stimulation in locus coeruleus (LC) in the rat model of depression-like behavior.Methods The depression-like behavior model was established by combining separation and chronic unpredictable stress stimulations.After the model establishment,behavior tests were used to verify the success of modeling.NE release in the hypothalamus induced by electrical stimulation in LC was studied in real time and NE signal was recorded with carbon fiber electrode.The peak value,the time to peak and half-life period of NE signal in both group rats were measured and analysed.Results The bodyweight,score of open-field test,percentage of sucrose preference of model group rats ((263.9± 16.4) g,(19.4±7.9),(44.3± 10.8) ％) were significantly lower than those((314.3±24.3) g,(53.3± 19.0),(60.6± 13.3) ％) of control group(P＜0.01).The peak value of NE signal in the hypothalamus induced by electrical stimulation in locus coeruleus in depression-like behavior model rats((176.9±50.4) pA)was less than that((361.6±88.6) pA)in control group(P＜0.01),and the time to peak of NE signal was also shortened in depression-like behavior model group rats (P＜0.05).Intraperitoneal injection of yohimbine (3 mg/kg) potentiated electrical stimulation induced NE release in depression-like behavior model rats but not in control group.Conclusion The chronic unpredictable stresses attenuate the secretion of NE in the hypothalamus induced by electrical stimulation in LC in rats.Yohimbine,a presynaptic α2 receptor antagonist,increased NE release in hypothalamus in depression-like behavior model rats.These findings suggest that the LC projects functionally to the hypothalamus and the projection may contribute to the pathogenesis of depression.

Practice and experience in teaching neurobiology / 中华医学教育探索杂志

Neurobiology,one of the important subject in life science frontier,comprises extensive and comprehensive contents.It is significant and essential for each discipline of medicine to offer this course.During last several years of teaching and practice,some methods,skills and ideas have been utilized and summarized.Modem medical education,by offering this course,will accord with the development concept of the transition from biomedicine to bio-psycho-social medical model,and this course will provide the substantial foundation for cultivating qualified medical students.

The correlation study on active avoidance behavior and electroencephalogram in rat with chronic unpredictable stress / 中华行为医学与脑科学杂志

Objective To investigate whether there is correlation exists in the effection of chronic unpredictable stress on active avoidance behavior and electroencephalogram ( EEG) of rat. Methods Twenty male SD rats (weight～200 g) were randomly divided into control group( n= 10) and model group( n- 10). Rats in model group were subjected to chronic unpredictable stress . Active avoidance response were observed with GeminiTM avoid system and EEG power spectrum was evaluated with Powerlab system. Results The failure rate in active avoidance test was correlation with delta wave power in EEG. Compared with control group, rats in model group had reduced failure rate in active avoidance task(42 ±36)% vs (82 ±30)% , P＜0.05). The EEG power spectrum of model group rats increased in delta band((47.09 ±22.86)μV2 vs (22. 55 ± 11. 57) μV2, P＜0. 05), which had the significant difference between the two group rats. The failure rate of active avoidance task in model group rats was positive correlation with EEG power spectrum of delta wave (r = 0. 717, P ＜ 0. 05) . Conclusion Chronic unpredictable stress facilitated active avoid behavior and changed spontaneous EEG, which suggested chronic unpredictable stress actived the neurotransmitter network system involved with active avoidance task in central nervous system. Brain cognitive function correlated positively with brain electrophysiology activity measured in chronic unpredictable stress induced rat model.

Effects of sodium nitroprusside on glutamate-induced responses of supraoptic nucleus neurons in vitro / 中国药理学通报

Aim To realize the modulatory actions of nitric oxide(NO) on supraoptic nucleus(SON)neurons by observing the effects of NO donor sodium nitroprusside(SNP) on the SON neurons. Methods The cell electrophysiology properties were obtained by the intracellular recording techniques from the SON neurons in adult rat hypothalamic slices. Results Local pressure ejection of glutamate induced depolarizing responses with decrease of input resistance, concentration- and membrane potential-dependent properties in 12 SON neurons. The amplitude and duration of glutamate responses were suppressed by bath of SNP in 67% of tested cells(P

Inhibitory and excitatory effects of sodium nitroprusside on supraoptic nucleus neurons in vitro / 中国临床药理学与治疗学

AimTo realize the regulatory actions of nitric oxide(NO) on supraoptic nucleus (SON) neurons by observing the effects of NO donor sodium nitroprusside(SNP) on SON neurons. Methods The cell electrophysioloical properties were obtained by the intracellular recording techniques from the SON neurons in adult rat hypothalamic slices. Results In 11 silent cells, superfusion of SNP(1 mmol · L-1) for 3～5 min resulted in the depolarization response with a decrease of membrane resistance and time constant(P＜0.05) in 55% of cells, while hyperpolarization with an increase of membrane resistance in 45 % of neurons. In 73% of tested cells, SNP also decreased the amplitude, overshoot, firing frequency and slope of current-voltage curve, and increased the afterhyperpolarization of action potentials evoked by intracellular depolarizing current pulses(P ＜0.05).However, SNP enhanced the spontaneous firing in 67% of 6 tested cells with spontaneous activities. ConclusionSNP presents an inhibitory or excitatory effect on SON neurons in aneurontype-andfunctionalstate-dependent manner, which suggests that NO may exhibit adverse regulatory actions on SON neurons.

Effects of psychological stress on pathogenetic condition and rapeutic effect of ulcerative colitis / 中国临床药理学与治疗学

AIM: To investigate the effects of psychological stress on ulcerative colitis rats and to explore the mechanisms of this;meanwhile to investigate the effects of anxiolytic drug on symptoms of ulcerative colitis rats under psychological stress and the mechanisms of it.METHODS: eighty male Wistar rats were randomly divided into four groups(n=20): UC control group;UC stress group;UC+clonazepam group;UC stess+clonazepam group.After UC model was established with immunization,these rats were fightened by cat to set up psychological stress model.During establishing stress model,each groups were respectively received physiologic saline or clonazepam by intragastric administration.After 15d treatment,all rats were sacrified simultaneously.Colon mucosal inflammationand damage were assessed by measuring colon mass,morphologic damage score,colonic MPO and NO activity levels.Morphologic damage score was examined under microscope.Colonic MPO and NO was measured by spectrophotometric method.Serum hydrocortisone was determined by radioimmunoassay(RIA).RESULTS: Morphologic damage score,colonic MPO and NO,serum hydrocortisone of UC stress group were significantly increased compared with those of UC control group;morphologic damage score,colonic MPO and NO,serum hydrocortisone of UC+clonazepam group were decreased markedly vs UC stress group;Little difference was observed between UC+clonazepam group and UC control group.CONCLUSION: Psychological stress can aggravate symptoms of UC.Although benzodiazepine have no anti-inflammatory action,it relieve effects on internal organs of psychological stress and aggravation of symptoms of UC by to effect limbic system and formatio reticularis.

Enhancement and depression of cholinergic transmission by 9-amino-1,2,3,4-tetrahydroacridine in rat superior cervical ganglia / 中国药理学通报

Using the conventional intracellu-lar recording techniques in the rat superior cervical ganglion, the effects of 9-amino-1,2,3,4-tetrahydroacridine(THA) on cholinergic transmission were studied. By superfusion of THA 0. 1~1 ?mol ?L-1(n = 26), the f-EPSPs evoked by preganglionic stimulation were facilitated, while 50~100 ?mol-L-1(n= 17) inhibited in a concentration-dependent manner, but 10 ?mol?L-1in 46% cells (n=11) increased and another 54% inhibited. Also exogenous ACh-induced potentials (n=27) were enhanced with THA 0. 1~10 ?mol?L-1, and in 60% (n=10) with 50~100 ?mol?L-1but another 40% depressed. In 7 cells, no enhancement of carbachol-inducedpotentials were found with THA 1~100 ?mol-L-1, while depression in 5 cells by 50~100 ?mol?L-1was observed. Pretreatment of atropine (1?mol?L-1) only partially eliminated THA inhibition on f-EPSPs but not ACh-or carbachol-induced potentials. It was suggested that THA facilitated cholinergic transmission by its anti-cholinesterase action and inhibited by both pre-and postsynaptic mechanism at different concentration levels.