盐酸多奈哌齐对血管性痴呆模型小鼠海马神经元ERK表达的影响

目的探讨盐酸多奈哌齐对血管性痴呆(VD)模型小鼠海马神经元中细胞外信号调节激酶(ERK)表达的影响。方法采用双侧颈总动脉反复缺血-再灌注法制备小鼠VD模型。将小鼠随机分为假手术组、模型组及盐酸多奈哌齐治疗组,药物组给予盐酸多奈哌齐灌胃治疗。术后第29、30天,采用跳台试验和水迷宫试验对各组小鼠进行行为学成绩测试,采用免疫组化法观察各组小鼠海马神经元ERK表达的变化。结果盐酸多奈哌齐可明显改善VD模型小鼠学习、记忆成绩(P<0.05)。模型组小鼠海马CA1区ERK1、ERK2表达及海马CA3区p-ERK表达较假手术组及治疗组减少(均P<0.05)。结论盐酸多奈哌齐通过增加乙酰胆碱含量,后者作用于毒蕈碱乙酰胆碱受体(M受体)激活ERK,从而有助于改善学习和记忆功能。海马神经元内ERK的表达减少可能参与了VD的发病机制。     

藏红花素通过调控cGMP/PKG通路对癫痫大鼠的神经保护及对海马神经元兴奋性的影响

目的 观察藏红花素对癫痫大鼠的神经保护及对海马神经元兴奋性的影响。方法 取45只大鼠,随机选取10只设为健康组,剩余35只建立癫痫模型,成功30只。随机分为癫痫组(10只)、藏红花素组(10只)、抑制剂组(10只); 藏红花素组腹腔注射藏红花素(50 mg/kg); 抑制剂组腹腔注射藏红花素(50 mg/kg),髓鞘注射ODQ[1H(1,2,4)oxadiazolo(4,3 α)quinoxaline 1 one] [环磷酸鸟苷(Cyclic guanosine monophosphate,cGMP)/cGMP依赖性蛋白激酶(cGMP-dependent protein kinase,PKG)通路抑制剂](10 μg/只); 健康组、癫痫组腹腔注射等体积生理盐水; 1次/d,干预14 d; 检测血清氧化应激反应水平指标; 检测神经元钙离子水平; 用原位末端标记法(Terminal deoxynucleoitidy transferase mediated nick end labeling,TUNEL)检测海马神经元凋亡率; 用免疫印迹法检测海马组织cGMP,PKG、磷酸化-PKG(Phosphorylation-PKG,p-PKG)蛋白表达水平。结果 与癫痫组比较,藏红花素组血清丙二醛(Malondialdehyde,MDA)水平、海马神经元内钙离子水平、海马神经元凋亡率降低,血清超氧化物歧化酶(Superoxide dismutase,SOD)活性水平、海马组织cGMP蛋白表达水平、p-PKG/PKG升高(P<0.05); 与藏红花素组比较,抑制剂组血清MDA水平、海马神经元内钙离子水平、海马神经元凋亡率升高,血清SOD活性水平、海马组织cGMP蛋白表达水平、p-PKG/PKG降低(P<0.05)。结论 藏红花素可抑制海马组织氧化应激,降低海马神经元兴奋性,保护神经功能,推测其作用机制可能与激活cGMP/PKG信号通路有关。     

血管性痴呆小鼠海马ERK2及p-ERK的表达特征

目的观察血管性痴呆（VD）小鼠海马中细胞外信号调节激酶（ERK2、p-ERK）的表达变化,探讨其在VD发病中的作用机制。方法采用双侧颈总动脉反复缺血-再灌注法制备小鼠VD模型,设立假手术组作为对照。术后第29、30天,经跳台试验和水迷宫试验对各组小鼠进行行为学成绩测试,用免疫组化方法观察各组小鼠海马CA1区ERK2及海马CA3区p-ERK的表达变化。结果VD模型小鼠学习、记忆成绩较假手术组显著下降（P〈0.05）;模型组小鼠海马CA1区ERK2的表达及海马CA3区p-ERK的表达较假手术组减少,差异有统计学意义（P〈0.05）。结论海马神经元内ERK的表达减少可能参与了血管性痴呆的发病机制,因此应用能促进ERK表达的药物可能成为治疗VD的有效方法之一。     

Effects of propofol on amino acid neurotransmitter levels and neuronal apoptosis in the hippocampus in a rat model of ischemia/reperfusion injury

BACKGROUND： Excitatory amino acids including glutamic acid and aspartic acid play a neurotrophic role during early development of the central nervous system but go on to promote toxic effects. Inhibitory amino acids include γ-aminobutyric acid and glycine. Changes in their concentration can reflect the degree of injury to brain tissue after cerebral infarction. OBJECTIVE： To investigate the effects of propofol on amino acid neurotransmitter levels and neuronal apoptosis in the hippocampus in a rat model of ischemia/reperfusion injury. DESIGN： Randomized controlled animal study. MATERIALS： Sixty male Wistar rats were randomly divided into a sham operation group, model group and propofol （50, 100 and 150 mg/kg） groups （n = 12）. METHODS： Global brain models of ischemia/reperfusion injury were established in the model group and the propofol groups. The vertebral artery and common carotid artery were merely isolated in the sham operation group. Ten minutes before ischemia, rats in the propofol groups were induced with an intraperitoneal injection of propofol （50, 100 or 150 mg/kg）; rats in the model and sham operation groups were induced with an intraperitoneal injection of saline （5 mL）. MAIN OUTCOME MEASURES： Content of amino acids, neuronal apoptotic index and density of apoptotic neurons in the hippocampal CA1 region. RESULTS： After a 10-minute ischemia / 60-minute reperfusion, the content of glutamic acid and aspartic acid was significantly decreased in the propofol （50, 100 and 150 mg/kg） groups compared with the model group （P 〈 0.05 or P 〈 0.01）; but the content of γ-aminobutyric acid was significantly increased in the propofol （100 and 150 mg/kg） groups （P 〈 0.05）. After a 72-hour reperfusion, the neuronal apoptotic index was significantly decreased in the propofol （50, 100 and 150 mg/kg） groups compared with the model group （P 〈 0.05 or P 〈 0.01 ）, and the decrease was remarkable in the propofol （100 and 150 mg/kg） groups. After a 72-hour     

血管性痴呆小鼠海马细胞外信号调节激酶表达的变化

目的:观察血管性痴呆(VD)小鼠海马中细胞外信号调节激酶(ERK1、p-ERK)的表达特征,探讨其在VD发病中的作用机制。方法:采用双侧颈总动脉反复缺血-再灌注法制备小鼠VD模型,设立假手术组作为对照。术后第29、30天,经跳台试验和水迷宫试验对各组小鼠进行行为学成绩测试,用免疫组化方法观察各组小鼠海马CA1区ERK1及海马CA3区p-ERK的表达变化。结果:VD模型小鼠学习、记忆成绩较假手术组显著下降(P<0.05)。模型组小鼠海马CA1区ERK1的表达及海马CA3区p-ERK的表达较假手术组减少,均有显著性差异(P<0.05)。结论:海马神经元内ERK的表达减少可能参与了血管性痴呆的发病机制,因此应用能促进ERK表达的药物可能成为治疗VD的有效方法之一。     

活血益智片对血管性痴呆大鼠海马区环氧化酶-2、核因子-κB表达的影响

目的观察活血益智片对血管性痴呆(VD)大鼠行为学改变及海马区环氧化酶-2(COX-2)、核转录因子-κB(NF-κB)表达的变化,探讨其对VD大鼠脑保护作用的可能机制。方法反复缺血再灌注建立血管性痴呆大鼠动物模型,60只雄性SD大鼠随机分为:假手术组、模型组和活血益智片低剂量(1.55g/kg)组、中剂量(3.1g/kg)组、高剂量(6.2g/kg)组、甲磺酸二氢麦角毒碱片(5.4mg/kg)组。Y迷宫及Morris水迷宫实验检测认知行为学改变,Western blot法检测大鼠海马区COX-2、NF-κB的表达。结果活血益智片可以显著提高血管性痴呆大鼠的学习记忆力和反应能力;与假手术组相比,模型组COX-2、NF-κB表达明显增高,活血益智片组可降低其表达。结论活血益智片可以明显改善血管性痴呆大鼠的行为学症状,可能是通过抑制大鼠脑组织COX-2、NF-κB的表达发挥其脑保护作用。     

盐酸多奈哌齐对血管性痴呆小鼠海马神经细胞神经元蛋白激酶C表达变化的影响

目的探讨盐酸多奈哌齐对血管性痴呆（Vascular dementia,VD）小鼠海马神经元蛋白激酶C（protein kinase C,PKC）变化的影响。方法将3月龄雄性昆明小鼠随机分为假手术组、模型组、多奈哌齐治疗组。采用双侧颈总动脉结扎,反复缺血-再灌注制备VD模型,药物治疗30d。术后第29、30天,分别进行跳台试验和水迷宫试验观察各组小鼠行为学改变。采用免疫组织化学法观察各组海马CA1区神经元PKC表达的变化。结果药物治疗组小鼠学习、记忆成绩较模型组明显改善（P〈0.05）。模型组PKC免疫反应阳性神经元平均光密度值为（0.2730±0.0709）,与假手术组（0.3206±0.0642）和药物组（0.3036±0.0688）相比均显著降低（P〈0.05）,而药物组与假手术组间无明显差别（P〉0.05）。结论反复缺血-再灌注导致VD小鼠海马神经元PKC表达减少;多奈哌齐通过抑制中枢神经系统中乙酰胆碱的降解,可增加VD小鼠海马神经元PKC表达,从而改善VD小鼠学习、记忆能力,推测此也是该药物改善VD小鼠学习、记忆障碍的一个重要环节。     

宽叶缬草对血管性痴呆小鼠学习记忆及海马区神经元病理学改变的影响

目的:观察宽叶缬草对血管性痴呆模型小鼠学习记忆及海马区神经元病理学改变的影响。方法:采用反复夹闭双侧颈总动脉结合腹腔注射硝普钠的方法复制小鼠拟血管性痴呆的模型。健康昆明小鼠54只,随机分为3组:假手术组、血管性痴呆模型组、宽叶缬草组。分别于术后7、15、30 d,跳台实验检测其痴呆程度;透射电镜、HE和Nissl染色对海马区神经元病理学改变进行观察。结果:宽叶缬草组跳台实验潜伏期明显短于模型组(P<0.01),受电击总时间少于模型组(P<0.01);宽叶缬草组海马CA1区神经元数量明显多于模型组(P<0.01);模型组可见神经元脱失、部分神经细胞核固缩并有胶质细胞增生等病理学改变。结论:宽叶缬草能明显减轻血管性痴呆小鼠海马CA1区神经元损伤,改善脑缺血引起的学习记忆障碍。     

依达拉奉对海人酸致颞叶癫痫大鼠海马神经元的保护作用

目的本实验观察依达拉奉对海人酸致痫大鼠海马神经元损伤的保护作用。方法选用成年健康雄性Wistar大鼠18只,体重260±20g。实验动物随机分为3组,①sham组(n=6):右侧海马CA3区注入等量的生理盐水;②KA模型组(n=6):右侧海马CA3区注入KA 4μg.kg-1(4μg/μl);③依达拉奉组(n=6):右侧海马CA3区注入KA 4μg.kg-1(4μg/μl)后,即刻给予依达拉奉10mg.kg-1.d-1腹腔注射。于大鼠注药或假手术后立即观察各组大鼠的行为学表现,于7d断头取脑,石蜡切片进行硫堇染色,于光学显微镜下观察注药对侧(左侧)海马CA1、CA3区及CA4门区组织形态学特征,并对其进行组织学分级。结果 Sham组大鼠注射对侧海马CA1、CA3和CA4门区无明显组织损伤,组织学分级多为0～1级,ND值为198±20.62和212±30.14;模型组KA致痫大鼠可见明显的组织损伤,组织学分级多为2～3级,ND值为79±13.72和90±14.98,与sham组相比,组织学分级显著升高(p<0.05),ND值显著降低(p<0.01)。依达拉奉组大鼠海马CA1区可见少量、散在性神经元坏死,组织学分级多1～2级,ND值为101±16.85和135±12.17。与模型组相比,组织学分级降低(p<0.05),ND值显著升高(p<0.05)。结论依达拉奉能够减轻KA致痫大鼠海马神经元的损伤,对神经元具有保护作用。     

γ-氨基丁酸对慢性脑缺血致血管性痴呆大鼠学习记忆能力的影响

目的观察γ-氨基丁酸（GABA）对慢性脑缺血致血管性痴呆（VD）大鼠学习记忆能力及海马CA1区神经元形态学的影响。方法将SD大鼠随机分为假手术组、模型组、GABA组,采用双侧颈总动脉永久性结扎法建立VD模型。GABA组术后腹腔注射GABA0.5g.kg-1.d-1,连续注射60d;用Morris水迷宫实验检测大鼠空间学习记忆能力;Nissl染色观察大鼠海马CA1区神经元形态学变化。结果 GABA能明显改善VD大鼠学习记忆能力,也能减轻海马CA1区神经元损伤。结论 GABA能改善慢性脑缺血致VD大鼠的学习记忆能力,减轻海马神经元损伤可能是其机制之一。     

碱性成纤维细胞生长因子对血管性痴呆大鼠海马胆碱能神经元的影响

目的皮下注射碱性成纤维细胞生长因子(bFGF)于血管性痴呆大鼠,研究用药前后大鼠海马胆碱能神经元的变化。方法制作血管性痴呆(VD)大鼠模型,随机取用VD大鼠模型12只,分治疗组6只,痴呆组6只。另外,取假手术组6只。皮下注射bFGF于治疗组中血管性痴呆大鼠。治疗5周后,以Morris水迷宫定位航行试验和空间探索试验来检测大鼠的学习记忆能力,乙酰胆碱转移酶(ChAT)免疫组织化学染色观察海马CA1区胆碱能神经元数目的变化。结果治疗组大鼠海马CA1区胆碱能神经元数目较痴呆组明显增多。结论皮下注射bFGF后能迁移至海马,诱导海马产生具有ChAT活性神经元,所产生的ChAT活性神经元可能就是胆碱能神经元。     

Antidepressant-like effect of celecoxib piroxicam in rat models of depression

Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.     

Basic fibroblast growth factor improves learning and memory deficits in a mouse model of vascular dementia Associated with the role of free radicals clearance?

BACKGROUND:Basic fibroblast growth factor(bFGF)exhibits neuroprotective functions,but the possible mechanisms of bFGF on vascular dementia remain unclear.OBJECTIVE:To explore the neureprotective effects of bFGF on a mouse model of vascular dementia,with focus on oxidative damage.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Medical College of Beihua University from March to December 2008.MATERIALS:bFGF was purchased from Peprotech,USA.METHODS:A total of 80 healthy,Kunming mice were randomly assigned to control,sham-surgery,model,and bFGF groups.The model and bFGF groups were used to establish vascular dementia models by repetitive cerebral ischemia-reperfusion in a conscious state.In addition,bFGF group mice were intraperitoneally injected with bFGF(100 μg/kg)following model establishment,once a day for 7 consecutive days.MAIN OUTCOME MEASURES:The Morris water maze was used to determine the influence of bFGF on learning and memory abilities in vascular dementia mice.The pathomorphological changes in hippocampal CA1 neurons were observed by Nissl staining.Superoxide dismutase and malondialdehyde changes were analyzed using biochemical analysis methods.Annexin V-FITC/PI-double-labeled flow cytometry was used to detect neuronal apoptosis.RESULTS:Learning and memory functions in model mice significantly decreased,as characterized by prolonged latency and reduced time and number of platform crossings(P < 0.01,P < 0.05).Superoxide dismutase activity was significantly reduced,malondialdehyde content was significantly increased(P < 0.01),and hippocampal neuronal apoptosis was increased(P < 0.01)following vascular dementia,bFGF increased superoxide dismutase activity,decreased malondialdehyde content,and reduced hippocampal neuronal apoptosis(P < 0.01),which resulted in improved learning and memory in mice with vascular dementia.CONCLUSION:bFGF improved learning and memory deficits in mice with vascular dementia by reducing free radical injury and inhibiting hippocampal neuronal apoptosis.     

钾通道Kv4.2、Kv1.4在硫化氢后处理对大鼠短暂全脑缺血神经保护中的作用研究

目的研究硫氢化钠(sodium hydrosulfide,Na HS)后处理对短暂全脑缺血大鼠海马中钾通道Kv4.2和Kv1.4 mRNA表达变化的影响及其脑保护作用,从而探讨Na HS对大鼠短暂全脑缺血神经保护作用的机制。方法用4VO方法建立大鼠短暂性全脑缺血(transient global cerebral ischemia,t GCI)模型,大鼠被随机分配到3组,分别为:假手术组(sham)、t GCI组、Na HS后处理组。Na HS后处理组为t GCI之后1 d,给予大鼠腹腔注射Na HS 24μmmol/kg或者180μmmol/kg。通过尼氏染色与Neu N免疫染色确定海马神经元的死亡,通过RT-PCR方法检测海马组织Kv4.2和Kv1.4mRNA水平的表达变化。结果 (1)与t GCI组比较,在t GCI之后1 d给予24μmol/kg Na HS后处理使海马CA1区存活细胞数目显著增加,而高剂量的Na HS(180μmol/kg)后处理对t GCI大鼠海马CA1区则无明显的保护作用。(2)在Re 26 h和Re 48 h,海马组织中Kv4.2、Kv1.4的mRNA表达水平均明显低于假手术组(P<0.05)。在Re 26 h+Na HS组,kv4.2(1.24±0.08)和kv1.4(1.11±0.07)的mRNA表达水平均分别高于Re 26 h组的kv4.2(0.75±0.04)和kv1.4(0.79±0.06),差异均有显著性(P<0.05)。结论外源性Na HS可能通过上调大鼠t GCI后海马区Kv4.2和Kv1.4 mRNA的表达,从而导致膜电位超极化,降低神经元兴奋性和氧耗,继而保护神经元免受脑缺血损伤。     

Correlates of hippocampal neuron number in Alzheimer's disease and ischemic vascular dementia

The cornu ammonis 1 region of the hippocampus (CA1) sector of hippocampus is vulnerable to both Alzheimer's disease (AD)-type neurofibrillary degeneration and anoxia-ischemia. The objective of this article is to compare number and size of neurons in CA1 in AD versus ischemic vascular dementia. Unbiased stereological methods were used to estimate the number and volume of neurons in 28 autopsy-derived brain samples. For each case, the entire hippocampus from one cerebral hemisphere was sliced into 5mm slabs (5-7 slabs/case), cut into 50 microm sections, and stained with gallocyanine. Using the optical dissector, we systematically sampled the number and size of neurons throughout the extent of CA1 and CA2. The total number of neurons was significantly less in AD compared with ischemic vascular dementia (p < 0.02), but there was no significant difference in neuron size. The greatest loss of neurons was observed in two cases with combined AD and hippocampal sclerosis. Regardless of causative diagnosis, the number of CA1 neurons correlates with magnetic resonance imaging-derived hippocampal volume (r = 0.72; p < 0.001) and memory score (r = 0.62; p < 0.01). We conclude that although CA1 neuron loss is more consistently observed in AD than ischemic vascular dementia, severity of loss shows the expected correlation with structure and function across causative subtype. Reductions in magnetic resonance imaging-derived hippocampal volume reflect loss, rather than shrinkage, of CA1 neurons.     

海马锥体细胞的变化对血管性痴呆大鼠学习记忆能力的影响

目的研究海马锥体细胞的变化对血管性痴呆大鼠学习记忆能力的影响。方法将大鼠随机分成手术组及对照组,手术组制作血管性痴呆大鼠模型,30d后用Morris水迷宫检测两组大鼠学习记忆能力及HE染色检测海马锥体细胞数目的变化。结果手术组大鼠学习记忆能力明显下降,海马锥体细胞数目较对照组明显减少。结论血管性痴呆大鼠海马锥体细胞减少,学习记忆能力下降。     

Effect of treatment with choline alphoscerate on hippocampus microanatomy and glial reaction in spontaneously hypertensive rats

The influence of long term treatment with choline alphoscerate on microanatomy of hippocampus and glial reaction was assessed in spontaneously hypertensive rats (SHR) used as an animal model of cerebrovascular disease. Choline alphoscerate is a cholinergic precursor, which has shown to be effective in countering cognitive symptoms in forms of dementia disorders of degenerative, vascular or combined origin. Male spontaneously hypertensive rats (SHR) aged 6 months and age-matched normotensive Wistar-Kyoto (WKY) rats were treated for 8 weeks with an oral daily dose of 100 mg/kg of choline alphoscerate, 285 mg/kg of phosphatidylcholine (lecithin) or vehicle. On the hippocampus of different animal groups, nerve cell number and GFAP-immunoreactive astrocytes were assessed by neuroanatomical, immunochemical and immunohistochemical techniques associated with quantitative analysis. Treatment with choline alphoscerate countered nerve cell loss and glial reaction primarily in the CA1 subfields and in the dentate gyrus of the hippocampus of SHR. Phosphatidylcholine did not affect hypertension-dependent changes in hippocampal microanatomy. Both compounds did not affect blood pressure values in SHR. These data suggest that choline alphoscerate may play a role in the countering hippocampal changes induced by cerebrovascular involvement. The observation that treatment with choline alphoscerate attenuates the extent of glial reaction in the hippocampus of SHR suggests also that the compound may afford neuroprotection in this animal model of vascular brain damage.     

Quantitative changes in hippocampal microvasculature of chronically stressed rats: No effect of fluoxetine treatment

Exposure to chronic stress alters the number and morphology of neurons and glia in the hippocampal formation; however, little is known about possible changes in vasculature. Here, we examined the effect of chronic social defeat stress on hippocampal vascular supply in rats. Recent reports document that antidepressant treatment can influence angiogenesis in the hippocampus; therefore, we also studied the effect of antidepressant drug treatment on hippocampal capillarization. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) treatment during the last 4 weeks. Rat endothelial cell antigen‐1 (RECA‐1)‐labeling of capillaries and quantitative stereological techniques were used to evaluate the treatment effects on capillary number. Special attention was paid to analysis of the vascular supply of the subgranular zone, which is regarded as an important component of the neurogenic niche for adult hippocampal neurogenesis. Chronic stress significantly decreased the number of microvessels by 30% in all hippocampal subregions, whereas fluoxetine treatment had no influence on capillary number. Furthermore, chronic stress decreased the capillarization of the subgranular zone to a similar extent, indicating that chronic stress affects the vascular niche for adult hippocampal neurogenesis. However, fluoxetine treatment had no impact on capillarization in the subgranular zone. We also detected a decrease in hippocampal volume in the animals as a result of stress, which was mildly altered by fluoxetine treatment. These pronounced changes in vascular supply may explain why the hippocampus is more vulnerable to insults when chronic stress precedes or coincides with other harmful conditions. Reduced microvasculature may also contribute to hippocampal volume decrease in stress‐related disorders. © 2009 Wiley‐Liss, Inc.     

Neurons in the hippocampal CA1 region,but not the dentate gyrus,are susceptible to oxidative stress in rats with streptozotocin-induced type 1 diabetes

In this study, we investigated the effects of streptozotocin-induced type 1 diabetes on antioxidant-like protein-1 immunoreactivity, protein carbonyl levels, and malondialdehyde formation, a marker for lipid peroxidation, in the hippocampus. For this study, streptozotocin(75 mg/kg) was intraperitoneally injected into adult rats to induce type 1 diabetes. The three experimental parameters were determined at 2, 3, 4 weeks after streptozotocin treatment. Fasting blood glucose levels significantly increased by 20.7–21.9 m M after streptozotocin treatment. The number of antioxidant-like protein-1 immunoreactive neurons significantly decreased in the hippocampal CA1 region, but not the dentate gyrus, 3 weeks after streptozotocin treatment compared to the control group. Malondialdehyde and protein carbonyl levels, which are modified by oxidative stress, significantly increased with a peak at 3 weeks after malondialdehyde treatment, and then decreased 4 weeks after malondialdehyde treatment. These results suggest that neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress 3 weeks after malondialdehyde treatment.     

Prenatal stress causes gender-dependent neuronal loss and oxidative stress in rat hippocampus

Our purpose was to investigate the effects of prenatal stress on neuronal changes in the hippocampus and the possible involvement of oxidative stress in female and male rats. Female and male offspring (1-month-old), whose dams were restrained in middle or later pregnant stage (MS or LS), were studied to observe changes in the number of hippocampal neurons and the expression of neuronal nitric oxide synthase (nNOS) in the hippocampus. Both MS and LS induced an increase in the number of nNOS-positive expression in female and male offspring in the hippocampus; however, both MS and LS caused a significant decrease in the number of hippocampal neurons in the female, but not in the male offspring. In addition, significant increases in calcium content and oxidant generation were induced by LS in the hippocampal CA3 region in female rats. These data suggest that prenatal stress can cause oxidative stress and consequent damage to neurons, leading to neuronal loss in the brain of offspring during development.