ω-3 多不饱和脂肪酸对PTSD-SPS 大鼠空间学习记忆和海马神经元 溶酶体损伤的防护作用研究

目的:观察饲料中添加ω-3多不饱和脂肪酸对PTSD-SPS大鼠空间学习记忆能力及海马神经元溶酶体损伤的保护作用。方法:将48只健康成年雄性SD大鼠随机分为正常对照组、PTSD-SPS模型组、30%ω-3PUFAs+PTSD-SPS模型组、60%ω-3PU-FAs+PTSD-SPS模型组。采用Morris水迷宫测试方法,观察大鼠定位航行实验中逃避潜伏期及空间探索实验中靶象限活动时间的百分比及穿台次数。电子显微镜观察大鼠海马神经元超微结构变化。结果:与对照组相比,SPS模型组大鼠逃避潜伏期延长,第5天达到(39.12±7.34)s(P<0.05);第6天大鼠靶象限内活动时间百分比明显缩短及穿台次数减少,分别是10.01%±3.03%及(1.05±0.13)次;与SPS模型组对比,喂饲60%ω-3PUFAs的SPS组大鼠逃避潜伏期为(19.13±4.26)s(P<0.05),靶象限内活动时间百分比及穿台次数为25.56%±2.13%、(2.36±0.34)次(P<0.05)。电镜结果显示,喂饲ω-3PUFAs的SPS模型组大鼠海马神经元中溶酶体数量比SPS组明显减少,与对照组没有显著差异。结论:ω-3多不饱和脂肪酸可能通过减少海马神经元溶酶体的数量对PTSD-SPS大鼠学习记忆损伤起到一定的防护作用。     

SPS建立PTSD样大鼠旷场行为的改变及十味温胆汤的调节作用

目的:观察单次延长应激(single-prolonged stress,SPS)建立PTSD模型对实验大鼠模后7天后的旷场行为的变化以及中药复方十味温胆汤对其的调节作用.方法:采用旷场实验,观察不同处理组大鼠的行为改变情况.结果:模型组大鼠在直立次数、穿格次数、运动总距离、中央格停留时间方面均明显低于正常大鼠(P＜0.05),西药阿普唑组大鼠,经统计在直立次数、穿格次数、中央停留时间方面与模型组有明显差异(P＜0.05),而十味温胆汤组大鼠各项指标均明显高于模型组,其中穿格次数、中央格停留时间与模型组具有非常显著的差异(P＜0.01),且与正常组及西药组接近(P＞0.05).结论:本课题成功复制了PTSD样大鼠模型,所选取的中药复方十味温胆汤能显著改善PTSD样大鼠的情绪行为变化,其效用与西药阿普唑仑类似.     

慢性脑低灌注大鼠焦虑样行为与海马区域炎性细胞因子水平的相关性分析

目的:分析慢性脑低灌注(CCH)大鼠模型焦虑样行为和海马和血清炎性细胞因子水平的相关性。方法:将成年雄性Sprague-Dawley(SD)大鼠(200-220 g)分为两组(假手术(sham)和双侧颈总动脉结扎(BCCAO)组,每组N=40),分别给予BCCAO或者假手术。造模4周后,通过旷场实验和高架十字迷宫测试大鼠焦虑样行为;间接免疫荧光(Iba1和GFAP染色)和酶联免疫吸附实验(ELISA)分别测定海马CA1区胶质细胞激活和血清及海马区域白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、细胞粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1))水平。结果:旷场实验结果表明相比sham组,BCCAO组总穿行距离、中央区穿行距离和停留时间明显增多(P<0.05),高架十字迷宫实验中BCCAO组开臂停留时间和访问次数明显增加(P<0.05),闭臂停留时间显著缩短(P<0.05)。另外,相比sham组,BCCAO组大鼠海马CA1区胶质细胞明显激活,海马以及血清中炎性因子的表达水平均显著上调。Pearson相关性分析显示海马区域而非血清ICAM-1和VCAM-1水平与CCH大鼠焦虑样行为(中央区和开臂的停留时间)呈显著正相关(P<0.05)。结论:海马区域ICAM-1和VCAM-1升高与CCH大鼠焦虑样行为显著相关,可能参与CCH慢性期焦虑样行为的发生。     

焦虑性抑郁模型大鼠脑区单胺递质含量与神经因子表达的变化

目的研究焦虑性抑郁模型大鼠海马、杏仁核、前额叶皮质内单胺递质的含量变化及脑内神经营养因子的表达趋势,探讨其可能的发病机制。方法 60只SD大鼠随机分为正常对照组、溶媒对照组、焦虑模型组、抑郁模型组、焦虑性抑郁模型组,每组12只。采用慢性束缚应激联合皮质酮注射的方法建立焦虑性抑郁大鼠模型,造模时间为21 d,造模结束后采用高架十字迷宫测试,旷场实验,强迫游泳实验评价大鼠的焦虑和抑郁样行为,HPLC-ECD法检测大鼠海马、杏仁核、前额叶皮质的单胺递质5-HT、NE、DA含量,蛋白印迹法检测大鼠各脑区神经营养因子BDNF、NT-3的含量。结果焦虑性抑郁模型组大鼠在进入开臂的时间、次数、旷场中自主活动次数均与焦虑组相当,与对照组及抑郁组比较差异有显著性(P0.01或P0.05),在强迫游泳中的不动时间显著增加,与对照组及焦虑组对比差异有显著性(P0.01);同时,与对照组比较,焦虑性抑郁模型组大鼠海马5-HT、杏仁核及前额叶皮质区的5-HT和NE含量均显著下降(P0.01或P0.05);此外,与对照组比较,焦虑性抑郁模型组大鼠各脑区BDNF、NT-3含量显著下降(P0.01或P0.05),同时与焦虑组比较,BDNF含量显著下降(P0.05)。结论焦虑性抑郁模型组大鼠具有显著的焦虑及抑郁样行为,其发病机制可能与脑内海马、杏仁核、前额叶皮质区域的单胺递质含量降低及神经营养因子BDNF、NT-3表达下调有关。     

刺五加对抑郁症大鼠行为学的影响

目的:研究刺五加对抑郁症动物行为学的影响。方法:采用大鼠强迫游泳试验,确定实验中刺五加治疗组剂量。采用慢性温和性不可预知应激(CUMS)+孤养的方法复制大鼠抑郁模型,将48只SD雄性大鼠分为6组(n=8):正常对照组(NC)、空白对照组(BC)、实验对照组(EC)、刺五加浸膏治疗组(AS)、盐酸氯丙咪嗪治疗组(CH)及刺五加浸膏+盐酸氯丙咪嗪联合治疗组(A+C),观察大鼠糖水偏爱度、体重增长和行为学改变。结果:在强迫游泳实验中,一定剂量的刺五加浸膏能明显缩短大鼠水面停留时间,其中600mg/kg剂量作用最为显著。在CUMS+孤养抑郁模型动物实验中,与NC组相比,BC组和EC组中央格停留时间显著增加(P0.05),其它各项指标显著减少(P0.05),BC组和EC组间各项指标没有显著差异(P0.05);经过28天的治疗后,AS组的中央格停留时间和穿越格数,CH组的穿越格数和清洁运动次数有改善但与NC组相比仍有显著差异(P0.05),AS组、CH组的其余各项指标及A+C组的各项指标都恢复至NC组水平(P0.05)。结论:刺五加在改善抑郁模型大鼠快感缺乏和其他行为学变化方面的作用与盐酸氯丙咪嗪相似,在提高动物对周围环境的要求及对自身的关注度方面略优于盐酸氯丙咪嗪。联合用药能有效改善各种症状且效果优于单独用药。     

慢性炎性痛模型大鼠诱发焦虑抑郁样情绪行为观察

目的动态观察弗氏完全佐剂(CFA)诱导慢性炎性痛模型大鼠痛情绪的改变情况,探索慢性炎性痛模型大鼠诱导焦虑、抑郁情绪的时间差异性。方法所有实验大鼠随机分为空白对照组和模型对照组,模型对照组于足底注射CFA建立慢性炎性痛模型。动态观察各组大鼠造模前、造模后1,3,7,18和26 d机械缩足阈变化(PWTs);观察造模后28 d旷场实验(OF),29 d高架O迷宫实验(EZM),30 d新奇食物抑制实验(NSF),造模后12,20和31 d大理石掩埋实验(MBT),造模后17,25和35 d糖水偏爱度实验(SPT)中大鼠行为改变情况。结果造模后1 d,模型对照组大鼠PWTs显著降低(P 0. 01),且在整个实验过程中均显著低于空白对照组(P 0. 01)。模型对照组在OF中较空白对照组大鼠的中央区运动距离、中央区停留时间、中央区进入次数显著减少(P 0. 01);在EZM中较空白对照组大鼠的开放臂运动距离,开放臂停留时间,开放臂进入次数显著减少(P 0. 05);在NSF中较空白对照组大鼠摄食潜伏期明显增加(P 0. 05),且食物消耗量无明显差异(P 0. 05);而MBT仅模后31 d,模型对照组较空白对照组大鼠大理石埋藏数量显著增加(P 0. 05); SPT中模后各时间点模型对照组与空白对照组大鼠比较均无明显差异(P 0. 05)。结论 CFA诱发的慢性炎性痛模型大鼠在4周后可出现多种与焦虑样情绪相关的动物行为改变,但在5周内均并未观察到与抑郁样情绪相关的动物行为改变。     

前扣带皮层区域磷酸激酶Czeta在弗氏安全佐剂致炎性痛大鼠情绪反应中的作用

目的观察CFA致炎性痛模型大鼠的情绪反应,探讨前扣带皮层(ACC)磷酸激酶Czeta(PKCzeta)与炎性痛大鼠情绪反应的关系。方法 24只清洁级雄性SD大鼠随机分为空白对照组和模型对照组。足底皮下注射弗氏完全佐剂建立慢性炎性痛模型。动态观察各组大鼠造模前(base)、造模后3、7、14、21和28 d的体重和痛阈变化;观察造模后14、21、28 d所有大鼠在高架O迷宫中的总运动距离、开放臂运动距离、开放臂进入次数和开放臂停留时间百分比。观察造模后14、29 d所有大鼠在旷场中的总运动距离、中央象限运动距离、中央象限进入次数和中央象限停留时间。采用免疫印迹法检测造模后14 d和29 d健侧和患侧ACC区域PKCzeta蛋白表达。结果各个时间点两组大鼠体重差异无显著性(P0.05)。造模前,两组大鼠痛阈差异无显著性(P0.05);造模后1 d,模型对照组大鼠痛阈显著降低(P0.05),且在整个实验过程中均显著低于空白对照组(P0.05)。与空白对照组比较,模型对照组大鼠于模后28 d开放臂运动距离和开放臂停留时间百分比显著减少(P0.05),于模后29 d中央象限运动距离和中央象限进入次数明显减少(P0.05)。造模后29 d,模型对照组大鼠患侧ACC区域PKCzeta蛋白表达明显多于空白对照组(P0.05)。且开放臂运动距离、开放臂停留时间百分比、中央象限运动距离、中央象限进入次数与患侧PKCzeta蛋白表达变化呈负相关。结论 CFA诱导的慢性炎性痛大鼠可出现异常情绪行为;慢性炎性痛情绪样行为可能与ACC区域PKCzeta的高表达相关。     

1ω-3不饱和脂肪酸对视网膜新生血管的实验研究

目的:研究ω-3不饱和脂肪酸对鼠视网膜新生血管的作用。方法:32只7日龄Wistar白鼠分为4组。每组各8只,分别与母鼠共同饲养,制备早产儿视网膜病变(ROP)视网膜新生血管动物模型,其中A组为ROP模型对照组,B、C、D组为ω-3PUFAs喂养组,分别按母鼠公斤体重给与ω-3PUFAs2.5mg/kg/d、7.5mg/kg/d及15mg/kg/d喂养。采用免疫组化观察小鼠中突破视网膜内界膜CD31的特异性表达,Western印迹法检测视网膜标本中RGS5的表达。结果:免疫组化观察视网膜CD31的特异性表达,A、B、C、D组突破视网膜内界膜的新生血管内皮细胞核数分别为(17.25±1.04)个、(15.75±1.83)个、(9.75±1.49)个、(8.5±1.69)个;免疫印迹法检测各实验组视网膜RGS5结果:A组与C组、A组与D组比较差异均有显著意义((P<0.001),其中A、B组相比较;C、D组相比较差异无显著意义(P>0.05)。结论:一定剂量的摄入量后对于新生鼠视网膜新生血管病变将起到一定的防治作用。     

SHR、WKY大鼠与SD大鼠注意缺陷多动障碍模型行为学特征的比较

目的比较SHR、WKY、SD大鼠行为学特征,探寻研究SHR大鼠注意缺陷多动障碍(ADHD)理想的对照模型。方法运用旷场实验统计大鼠运动距离、运动速度、穿格数及理毛次数来评价SHR、WKY、SD大鼠自主运动情况;运用水迷宫实验检测三组大鼠的学习记忆能力。结果旷场实验结果显示,SHR大鼠在总运动量、平均运动速度及穿格次数上较WKY及SD大鼠均显著增加(P0.01);与WKY大鼠相比,SD大鼠运动距离显著高于WKY组(P0.01),其运动速度及穿格数略高于WKY组(P0.05);水迷宫隐匿站台实验中,与SHR大鼠相比,SD大鼠潜伏期较长(P0.05),在潜伏期运动距离上,SD大鼠在训练第1天、第3天及第4天运动距离较SHR大鼠延长(P0.05或P0.01);比较WKY组,SD大鼠潜伏期及潜伏期运动距离较WKY在各个训练时间均有不同程度的下降(P0.05或P0.01)。在空间探索阶段,SD大鼠穿台次数及目标象限运动时间、距离比率等均较SHR大鼠有所减少(P0.05),而较WKY大鼠则有不同程度的升高(P0.05或P0.01)。结论 WKY大鼠与SHR大鼠行为学差异过大,两者的比较存在一定的不足,增设SD大鼠作为SHR大鼠的对照组能够提升SHR大鼠行为学特征的可比性,更为客观的反映SHR大鼠的行为学特征。     

利多卡因对异氟醚麻醉后大鼠海马组织炎症及认知功能的影响

目的:研究利多卡因对异氟醚麻醉后大鼠海马区炎症因子、神经活性物质及认知功能的影响。方法:60只老龄SD大鼠随机分为3组:异氟醚组、利多卡因+异氟醚组、对照组各20只,建立大鼠吸入麻醉模型。利多卡因+异氟醚组给予静脉注射利多卡因,其他组给予生理盐水作为对照。麻醉结束后24 h Morris水迷宫实验评价大鼠认知功能,ELISA法检测大鼠海马组织炎症因子和神经活性物质。结果:与对照组相比,异氟醚组Morris水迷宫逃避潜伏期延长(P0.05),平台象限停留时间及穿越平台次数减少(P0.05),海马组织TNF-α、IL-6、IL-1β水平升高(P0.05),NT-3、NGF、BDNF水平降低(P0.05)。利多卡因明显缩短异氟醚麻醉大鼠的逃避潜伏期并增加其平台象限停留时间及穿越平台次数(P0.05),降低海马组织炎症水平(P0.05),升高神经活性物质水平(P0.05)。结论:利多卡因可明显缓解异氟醚麻醉后大鼠海马组织的炎症反应并升高海马组织神经活性物质水平,改善认知功能障碍。     

One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. The present study was designed to examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience.     

Influence of omega-3 Fatty Acid status on the way rats adapt to chronic restraint stress

Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.     

Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice

Neuropeptide Y (NPY) acting through Y1 receptors reduces anxiety- and depression-like behavior in rodents, whereas Y2 receptor stimulation has the opposite effect. This study addressed the implication of Y4 receptors in emotional behavior by comparing female germ line Y4 knockout (Y4−/−) mice with control and germ line Y2−/− animals. Anxiety- and depression-like behavior was assessed with the open field (OF), elevated plus maze (EPM), stress-induced hyperthermia (SIH) and tail suspension tests (TST), respectively. Learning and memory were evaluated with the object recognition test (ORT). In the OF and EPM, both Y4−/− and Y2−/− mice exhibited reduced anxiety-related behavior and enhanced locomotor activity relative to control animals. Locomotor activity in a familiar environment was unchanged in Y4−/− but reduced in Y2−/− mice. The basal rectal temperature exhibited diurnal and genotype-related alterations. Control mice had temperature minima at noon and midnight, whereas Y4−/− and Y2−/− mice displayed only one temperature minimum at noon. The magnitude of SIH was related to time of the day and genotype in a complex manner. In the TST, the duration of immobility was significantly shorter in Y4−/− and Y2−/− mice than in controls. Object memory 6 h after initial exposure to the ORT was impaired in Y2−/− but not in Y4−/− mice, relative to control mice. These results show that genetic deletion of Y4 receptors, like that of Y2 receptors, reduces anxiety-like and depression-related behavior. Unlike Y2 receptor knockout, Y4 receptor knockout does not impair object memory. We propose that Y4 receptors play an important role in the regulation of behavioral homeostasis.     

Anxiolytic-like effects of sinapic acid in mice

Sinapic acid is a phenylpropanoid compound and is found in various herbal materials and high-bran cereals. With the exception of its antioxidant activities, the pharmacological properties of sinapic acid have been rarely reported. The purpose of this study was to characterize the putative anxiolytic-like properties of sinapic acid using an elevated plus-maze (EPM) and hole-board test. Control mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). Sinapic acid (4 mg/kg, p.o.) significantly increased the percentages of time spent in the open arms of the EPM test (P<0.05). In the hole-board test, sinapic acid also significantly increased the number of head-dips at 4 mg/kg (P<0.05). In addition, the anxiolytic-like properties of sinapic acid examined in the EPM test were blocked by flumazenil or bicuculline, which are GABA(A) antagonists. Moreover, sinapic acid markedly potentiated GABA current in single cortical neurons in a dose-dependant manner, and reactive I(GABA) increased to 1.8 times at 1 muM of sinapic acid. These results suggested that sinapic acid is a prominent anxiolytic agent, and that its anxiolytic-like effects are mediated via GABA(A) receptors and potentiating Cl(-) currents.     

大鼠内侧前额叶皮质内ERK1/2 活化参与脊髓损伤后抑郁情绪

目的:观察细胞外信号调节激酶1/2(ERK1/2)的活化在脊髓损伤引起抑郁中的作用。方法:应用Western blot和行为药理学方法,观察脊髓损伤后(SCI)大鼠内侧前额叶皮质内(mPFC)ERK1/2及磷酸化-ERK1/2(p-ERK1/2)的表达情况及ERK1/2磷酸化抑制剂U0126对抑郁样行为的影响。结果:脊髓损伤后的第2天到第8周,SCI模型大鼠的BBB评分均显著低于假手术组,差异具有统计学意义(p0.05)。脊髓损伤后8周-12周,SCI模型大鼠强迫游泳不动时间与假手术组相比明显缩短,mPFC内pERK1/2蛋白表达水平明显升高,总ERK 1/2的蛋白水平则未见组间差异,而给予U0126的大鼠的不动时间与给药之前相比明显延长增加,mPFC内pERK1/2蛋白表达水平较SCI模型大鼠明显降低,差异均具有统计学意义(P0.05)。结论:内侧前额叶皮质内ERK1/2的激活参与了脊髓损伤后引起的突触可塑性,在相关的抑郁样行为的产生中发挥了重要的作用。     

Role of free radicals in stress-induced neurobehavioural changes in rats

Effect of restraint stress (RS) and its modulation by antioxidants were evaluated on elevated plus maze (EPM) and open field (OF) tests in rats. Restraint stress (RS for 1 hr) reduced the number of open arm entries, as also the time spent on open arms indicating enhanced anxiogenic response in the EPM test as compared to normal non RS group of rats. Pretreatment with ascorbic acid (100 and 200 mg/kg) and alpha-tocopherol (30 and 60 mg/kg) attenuated these RS-induced effects. In the OF test, RS-reduced (a) ambulations; and (b) rearings, whereas an increase was seen in (a) latency of entry and (b) number of fecal boluses. The RS-induced changes in OF parameters were reversed after pretreatment with the antioxidants, (ascorbic acid and alpha tocopherol). Biochemical data showed that RS enhanced MDA levels in both serum and brain, and these were attenuated after pretreatment with the antioxidants. The pharmacological and biochemical results indicate that free radicals might be involved in such stress-induced neurobehavioural effects.     

Midazolam Ameliorates the Behavior Deficits of a Rat Posttraumatic Stress Disorder Model through Dual 18 kDa Translocator Protein and Central Benzodiazepine Receptor and Neurosteroidogenesis

Post-traumatic stress disorder (PTSD) is a debilitating anxiety disorder that may develop after an individual has experienced or witnessed a severe traumatic event. It has been shown that the 18 kDa translocator protein (TSPO) may be correlated with PTSD and that the TSPO ligand improved the behavioral deficits in a mouse model of PTSD. Midazolam, a ligand for TSPO and central benzodiazepine receptor (CBR), induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether midazolam ameliorates PTSD behavior in rats as assessed by the single prolonged stress (SPS) model. The SPS rats received daily Sertraline (Ser) (15 mg/kg, p.o.) and midazolam (0.125, 0.25, 0.5, and 1 mg/kg, p.o.) during the exposure to SPS and behavioral assessments, which included the open field (OF) test, the contextual fear paradigm (CFP), and the elevated plus-maze (EPM). The results showed that, like Ser (15 mg/kg, p.o.), midazolam (0.25 and 0.5 mg/kg, p.o.) significantly reversed the behavioral deficiencies of the SPS rats, including PTSD-associated freezing and anxiety-like behavior but not the effects on spontaneous locomotor activity. In addition, the anti-PTSD effects of midazolam (0.5 mg/kg, p.o.) were antagonized by the TSPO antagonist PK11195 (3 mg/kg, i.p.), the CBR antagonist flumazenil (15 mg/kg, p.o.) and the inhibitor of steroidogenic enzymes finasteride (30 mg/kg, p.o.), which by themselves had no effect on PTSD-associated freezing and anxiety-like behavior. In summary, this study demonstrated that midazolam improves the behavioral deficits in the SPS model through dual TSPO and CBR and neurosteroidogenesis.     

海马齿状回神经再生对WKY大鼠抑郁样行为的影响*

目的:观察海马齿状回(DG)神经再生对成年Wistar Kyoto(WKY)大鼠抑郁样行为的影响。方法:实验共分三个组(n = 10):①正常对照(Wistar)组:选取 9 周龄Wistar大鼠,给予生理盐水 3 周(10 mg/kg, 灌胃);②抑郁模型(WKY)组:选取同龄WKY大鼠并经行为学测定后筛选出抑郁大鼠作为抑郁模型组,给予生理盐水 3 周(10 mg/kg, 灌胃);③阳性对照(AMI+WKY)组:选取同龄WKY抑郁大鼠,给予阿米替林(AMI) 3 周(10 mg/kg, 灌胃)。选用免疫荧光染色细胞增殖标记物Ki67、未成熟神经元标志物DCX检测大鼠的海马神经再生水平;应用糖水偏好实验(SPT)、旷场实验(OFT)和强迫游泳实验(FST)检测各组大鼠的抑郁样行为学变化。结果:①WKY抑郁大鼠海马DG区细胞增殖标志物Ki67⁺细胞数和未成熟神经元标志物DCX⁺细胞数较Wistar大鼠分别降低了 33.0%(P＜0.01)和39.2%(P＜0.01);阿米替林给药后使抑郁大鼠海马DG区Ki67⁺细胞数和DCX⁺细胞数分别增加了43.8%(P＜0.01)和46.7%(P＜0.01)。②与Wistar大鼠相比,WKY抑郁大鼠糖水偏好程度明显降低(P＜ 0.01),旷场实验中运动总距离显著缩短(P＜0.01)和中心停留时间显著减少(P＜0.01),强迫游泳实验中不动时间明显延长(P＜ 0.01);阿米替林治疗可显著改善WKY大鼠的上述抑郁样行为。结论:①成年WKY抑郁大鼠的海马神经干细胞的增殖和分化能力较正常对照组显著降低,提示成年WKY抑郁大鼠的神经再生受损;②改善海马受损的神经再生可以部分逆转成年WKY大鼠的抑郁样行为。