慢性强迫游泳应激对实验大鼠类关联负变事件相关电位的影响

Objective To explore whether there were abnormalities of behavioral tests and CNV-like potential in stressed rats following repeatedly forced swim stress.Methods Forty male rats were randomly divided into 4 groups: the control groups (Control-1 and Control-2) and the stress groups ( Stress-1 and Stress-2).Rats in stress groups were administered to repeatedly forced swim 7 or 14 days respectively.Body weight gain, saccharin preference test and open field test were performed.After being anesthetized with urethane, CNV-like potentials were elicited by condition-test stimulus.Results Results of behavioral tests displayed less body weights (F =253.60, P＜0.001 ) and less saccharine solution intake (F= 13.67, P=0.001 ) in stressed group rats and significant effects of stress on the number of crossing squares, the duration of rearing and the number of grooming in open field test.CNV amplitudes were lower in the stressed rats than those in control (F=21.312, P＜0.01 ).Conclusion This study provides an important evidence of changes of CNV-like potential in depressed rats following repeatedly forced swim stress.Based on this study, ER Ps should be taken into consideration and applied as the useful tools in the research work of depressed animal models.     

Effects of unpredictable chronic stress on behavior and brain- derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

Background Brain-derived neurotrophic factor （BDNF） is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal （HPA） axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield （CA3） and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages （2 months and 15 months） were randomly assigned to six groups： two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field （OF） test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals （age： F=6.173, P〈0.05, stress： F=6.056, P 〈0.05）. Stress was the main factor affecting sucrose preference （F=123.608, P 〈0.05）. Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals （P 〈0.05）. The older stress rats showed a lower sucrose preference than young stress rats （P 〈0.05）. Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square （P 〈0.05）, exhibiting fewer vertical movements （P 〈0.05） and less grooming （P 〈0.05）. Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups （P〈0.05）, a reduction that was still present at the eighth day after stress （P〈0.05）. Stress and age were the main factors affecting the expression of BDNF （F=9.408, P 〈0.05; F=106.303, P 〈0.05）. The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point. Conclusion Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.     

Analysis of Age Dependent Effects of Heat Stress on EEG Frequency Components in Rats

Objective To demonstrate changes in different frequencies of cerebral electrical activity or electroencephalogram （EEG） following exposure to high environmental heat in three different age groups of freely moving rats. Methods Rats were divided into three groups （i） acute heat stress - subjected to a single exposure for four hours at 38 ℃; （ii） chronic heat stress exposed for 21 days daily for one hour at 38 ℃, and （iii） handling control groups. The digital polygraphic sleep-EEG recordings were performed just after the heat exposure from acute stressed rats and on 22nd day from chronic stressed rats by simultaneous recording of cortical EEG, EOG （electrooculogram）, and EMG （electromyogram）. Further, power spectrum analyses were performed to analyze the effects of heat stress. Results The frequency analysis of EEG signals following exposure to high environmental heat revealed that in all three age groups of rats, changes in higher frequency components （β2） were significant in all sleep-wake states following both acute and chronic heat stress conditions. After exposure to acute heat, significant changes in EEG frequencies with respect to their control groups were observed, which were reversed partly or fully in four hours of EEG recording. On the other hand, due to repetitive chronic exposure to hot environment, adaptive and long-term changes in EEG frequency patterns were observed. Conclusion The present study has exhibited that the cortical EEG is sensitive to environmental heat and alterations in EEG frequencies in different sleep-wake states due to heat stress can be differentiated efficiently by EEG power spectrum analysis.     

阿魏酸钠对慢性应激抑郁模型大鼠抗抑郁作用的实验研究

Objective To measure the antidepressive activity of sodium ferulate (SF) in chronic unpre-dictable mild stress (CUMS) rat model of depression. Methods Male Sprague-Dawley (SD) strain rats weighing 220～280g were divided into six matched groups (n=11 in each group ) based on their sucrose consumption in preliminary tests (1% sucrose solution) : control, CUMS(model) , CUMS + fluoxetine (FLU) ( positive control), and treatment ( CUMS + SF) groups. The rats in model group were exposed to CUMS for 28 days;the rats in posi-ly) for 28 days;the animals in treatment groups were exposed to CUMS and received administration of SF (20,40, care and received ip administration of normal saline simultaneously. The rats except control were housed separately in different rooms during the duration of the stress procedure. The rat model of depression was established by expo-sing to an unpredictable sequence of stressors;the body weight,food intake and fluid consumption were measured ;the behaviors were examined by open field and forced-swimming tests. A representative sections cutting across hip-pocampal area of the rats in the six groups were examined by light microscopy. Results The rat model of depres-sion has been established successfully at 28th day. The results showed that chronic ip administration of SF signifi-cantly reversed the effects of CUMS on the body weight gain,the consumption of sucrose solution,the squares cross-ing and rearing in open field test and the immobility time during forced-swimming test of the rats [(88.06±7.83) g vs. (77.15±14.66 )g;(66.33±3.03)g vs. (40.75±6.05)g;(25.10±4,90) times vs. (18.20±2.00) times, (6.60±1.20 ) times vs. (3.20±0.60) times ;(117.30±7.22) s vs. (148.10±8.25)s], the values of P were 0.0425,0.0087,0.0409,0.0317,0.0025 respectively,and also partially reversed the effects of CUMS on his-topathology of hippoeampus. Conclusion SF possesses potent antidepressant-like activity,and the antidepressant-like action may result from its neuroprotective effect.     

Astragaloside Ⅳ Protects Against Aβ1-42-induced Oxidative Stress,Neuroinflammation and Cognitive Impairment in Rats

Objective To investigate the neuroprotective action of astragaloside Ⅳ (AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42 (Aβ1-42) in rats and elucidate its underlying molecular mechanisms. Methods Adult-male Sprague-Dawley rats (230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳgroups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test (hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ (5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior software system. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer's instructions. The levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in tissue lysates were assayed with ELISA. Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳsignificantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia's rats. Conclusion Our findings suggest that AS-Ⅳ might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.     

Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats

Background The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats. Methods Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze （MWM）. The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique. Results The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group （P〈0.05）. The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group （P〈0.05）. The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group （P〈0.05）. Conclusions Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn, BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF/TrkB signal transduction pathways may participate in the process of the enhanced learning and memory durina chronic multiple stress.     

Effects of exercise on behavior and peripheral blood lymphocyte apoptosis in a rat model of chronic fatigue syndrome

This study examined the effects of exercise on behavior and peripheral blood leukocyte apoptosis in a rat model of chronic fatigue syndrome （CFS）. Thirty-six healthy male Sprague-Dawley rats were equally randomized into 3 groups： the control group, CFS model group and the exercise group in terms of body weight. A total of 25 rats entered the final statistical analysis due to 11 deaths during the study. CFS model was established by subjecting the rats in CFS model group and exercise group to electric shock, chronic restraint stress and cold water swim. Besides, rats in the exercise group took rtmning wheel exercise. After a week of conditioning feeding, model construction and running wheel exercise were performed simultaneously, and lasted for 23 consecutive days. The behavior experiments, including running wheel exercise, open-field test, tail suspension test and Morris water maze test, were conducted, either before or after the model establishment. Rats were sacrificed and peripheral blood was obtained for the assessment of lymphocyte apoptosis index by flow cytometry （FCM）. It was found that as compared with those in the control group, the weight of the rats was decreased obviously （P〈0.01）, the mobility time in the open-field and the tail suspension tests was shortened significantly （P〈0.01）, the time to locate the platform was enhanced （P〈0.01） and the cell apoptosis index was increased substantially （P〈0.01） in the CSF model group. Meanwhile, in comparison to the model group, the behavior in the open-field and the tail suspension tests was improved significantly （P〈0.05）, and the apoptosis index decreased remarkably （P〈0.01） in the exercise group. It is concluded that sport intervention can prevent lymphocyte apoptosis and improve animal behavior rather than the memory.     

萱草花对抑郁模型大鼠行为学及学习记忆的影响

Objective To observe the effects of the extract from daylily on the learning and memory in depression model rats, and to explore its possible mechanism. Methods Rats were randomly divided into control group, model group ( CUMS), the positive group (CUMS + fluoxetine) , high, medium and low dose group (stress + daylily extract in different doses), 12 rats in each group. The depression model was established by combining separation and chronic unpredictable stress. Body mass, open-field-test and sugar consumption experiment were used to evaluate the changes of behaviors in rats. And morris water Maze test was used to evaluate the ability of learning and memory. Results There was no statistically distinction between the rats of each group on weight and the behavioral indicator before modeling. Compared with the control group, the vertical movement,horizontal movement of open box test in the model group were reduced (P＜0.05 ) ,and sugar consumption and preference degree decreased (P<0.05 ).The target quadrant time, platform resident time, effective area residence time and crossing platform times in the water maze test of the model group was less than those of the control group. The daylily effect was evaluated at 0, 7, 14, 21, 28, 35, 42 days respectively post treatment. There were significant differences in depression behaviors between model group and daylily group(P＜0.05). And each indicator in the water maze test of the daylily group (high, medium dose) was more than that of model group (P ＜ 0. 05). Control group, model group, positive group, high, medium and low dose group, vertical movement scores were (41.83 ± 17.63; 8.14 ±4.23; 12.73 ±7.21; 23.17 ± 18.75; 8.38 ±3.46; 13.50 ±5.44); horizontal movement scores were (69.92 ±34.04; 28.33 ±20.36; 62.25 ± 15.72; 69.42 ±35.17 ; 49.08 ±32.85; 48.08 ±21.19). Conclusion Daylily may be partially work on the depression of rats, with some antidepressant effect, meantime,daylily can improve the ability of learning and memorizing of the depressed rats.     

Eiectroacupuncture Prevents Cognitive Deficits Caused by Topiramate （TPM） in Rats

Objective Recent studies have demonstrated that acupuncture is feasible to treat cognitive impairments. The objective of this study was to present behavioral evidence that electro-acupuncture （EA） could improve the learning and memory of TPM administrated rats. Methods The pattern of TPM-induced cognitive deficits in rats was made by administration of TPM intragastrically for 3 weeks. Of them the rats which showed damage in learning and memory （n=45） were randomly allocated to 3 groups： Impaired group （n=15）, EA group （n=15） and placebo-EA group （n=15）. Moreover, normal group （n=15） was set as control groups. EA stimulation was provided at acupoints located in either the midline of the back or of the head： Gv-20 （Baihui）, Gv-14 （Dazhui）. Morris water maze test was employed to assess spatial discriminative ability per group respectively and to analyze the curative effects of EA. Results Compared to the normal group, obvious cognitive deficits were found in the impaired and placebo-EA groups, and the statistic analysis showed that there were significant differences between normal and impaired groups in ANOVA. In the EA group, shortened mean escape latency was detected compared with the impaired effect on cognitive group during the same trial days; search strategy changed from random pattern adopted by impaired and placebo-EA rats to tendency or linear pattern popular in the normal group. Conclusion The present results suggested that EA exerted a protective impairment caused by TPM in rats, and EA has a specificity of cure. EA as a potential clinic method in treating TPM-induced cognitive impairment should be developed and investigated in the future.