Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study

We have investigated immunohistochemically the effects of melatonin on Leydig cells in rat. Three groups of Wistar rats were used. Rats in group I and II were sham-pinealectomized (control) and pinealectomized, respectively, whereas rats in group III were pinealectomized and injected daily with melatonin for 2 months. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum testosterone levels were determined with the use of a chemiluminescent enzyme immunoassay. Testicular tissue was collected and processed for semiquantitative evaluation of immunohistochemical testosterone staining. Intensity of immunostaining was determined on a scale between 0 (no staining) and 5 (heavy staining). In pinealectomized rats, serum testosterone levels were significantly increased as compared to sham-pinealectomized rats. Daily administration of melatonin after pinealectomy resulted in significant decreased serum testosterone levels as compared to levels in control and pinealectomized rats. Immunostaining of testosterone was moderate (3+) in sham-pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in pinealectomized rats that were treated with melatonin, respectively. The results of our study indicate that pinealectomy induces increased testosterone secretion in Leydig cells and this increased secretion can be prevented by administration of melatonin.     

Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats

Previous observations demonstrated that physiological levels of melatonin, the pineal secretory product, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects of pinealectomy and administration of exogenous melatonin on liver tissue in rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, reduced glutathione (GSH) levels and malondialdehyde (MDA) levels. Rats were divided into three groups (10 rats in each group): control (non-Px), Px+vehicle and Px+melatonin (4 mg/kg given daily intraperitoneally for 10 days). Liver GSH levels were significantly lower in Px rats than in the control group. Melatonin administration significantly increased GSH levels (p < 0.05). Px caused a significant increase in MDA levels as compared with the control group and melatonin administration to Px rats significantly reduced MDA levels in the liver (p < 0.05). Sinusoidal dilatation to a varying degree developed in all Px rats. Severity of mononuclear cell infiltration and sinusoidal congestion were lower in Px+melatonin group than in the Px group. These findings suggest that a significant increase in oxidative and structural changes occur in rat livers after pinealectomy, which can be diminished by melatonin treatment.     

松果体摘除及褪黑素对大鼠胸腺上皮细胞白细胞介素-7表达的影响

目的 探讨松果体摘除及褪黑素对大鼠胸腺上皮细胞白细胞介素7(IL-7)表达的影响及其意义.方法 1.培养大鼠胸腺上皮细胞,应用广谱角蛋白抗体进行免疫细胞化学显色鉴定;MTT法观察褪黑素(1×10-3～10-9mol/L)干预对细胞生长的影响;细胞分空白对照组、褪黑素10-8mol/L处理组和褪黑素10-6mol/L处理组,RT-PCR法观察细胞IL-7 mRNA的表达;2.选用清洁级雄性SD大鼠110只,分为正常对照组、假手术对照组、松果体摘除组、松果体摘除+褪黑素7.5ms/(kg·d)腹腔注射组和松果体摘除+褪黑素15mg/(kg·d)腹腔注射组.术后4周和8周取材,运用免疫组织化学和RT-PCR方法 观察胸腺上皮细胞IL-7表达的变化. 结果 褪黑素干预对大鼠胸腺上皮细胞的生长无显著影响,但能使IL-7 mRNA的表达水平呈剂量依赖性升高;松果体摘除对大鼠胸腺上皮细胞表达IL-7无显著影响,补充褪黑素15mg/(kg·d)4周后IL-7表达显著增高,8周后均下降至正常水平. 结论 松果体及褪黑素可能通过影响大鼠胸腺上皮细胞IL-7的表达,从而调节胸腺细胞的分化发育.     

白藜芦醇对糖尿病大鼠心功能障碍及酸性鞘磷脂酶-神经酰胺通路的影响

目的:观察白藜芦醇(RSV)对糖尿病大鼠心功能障碍的影响并探讨其与酸性鞘磷脂酶-神经酰胺通路的关系。方法:通过一次性腹腔注射小剂量链脲佐菌素(STZ;30 mg/kg)联合高脂饮食饲养12周构建2型糖尿病(T2DM)大鼠模型。实验分为正常对照(control)组、T2DM组、T2DM+RSV组(灌胃给予糖尿病大鼠白藜芦醇100 mg·kg~(-1)·d~(-1))和RSV组(正常大鼠灌胃给予同等容量RSV),共灌胃12周,每周称量体重并调整给药剂量。实验结束后,釆用小动物M型超声检测模型大鼠心脏功能、形态和结构的变化;颈动脉插管检测血流动力学变化;生化方法检测血清中糖、脂水平以及心脏组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;油红O染色和天狼星红染色分别观察心脏组织中脂肪堆积和心肌纤维化情况;高效液相质谱法检测心脏组织中神经酰胺(ceramide)含量;Western blot检测酸性鞘磷脂酶(ASMase)和过氧化物酶增殖体激活受体γ辅激活因子1α(PGC~(-1)α)的蛋白表达。结果:T2DM组大鼠空腹血糖、甘油三酯、胆固醇及低密度脂蛋白胆固醇水平均较control组显著升高,心功能显著降低(P0.05);T2DM组大鼠心脏组织中脂肪堆积、MDA含量显著增加(P0.05),SOD活性、ATP水平和PGC~(-1)α蛋白表达均显著降低(P0.05),且出现明显心肌纤维化;给予白藜芦醇治疗12周可显著改善以上指标的异常变化,同时,显著下调糖尿病大鼠升高的心肌ASMase蛋白和ceramide水平。结论:白藜芦醇可显著改善糖尿病诱导的大鼠心功能障碍和心肌纤维化,其机制可能与抑制ASMase-ceramide通路有关。     

Melatonin protects against epirubicin-induced cardiotoxicity

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.     

Effect of binge ethanol treatment on prooxidant-antioxidant balance in rat heart tissue

Binge drinking of alcohol is known to cause cardiac dysfunction in some drinkers. This study was designed to examine the effect of ethanol on rat heart tissue with an experimental model mimicking human binge drinking. Female Sprague-Dawley rats were given ethanol diluted with normal saline (40%, v:v) by gavage at the dose of 5.0g/kg every 12h for 3 doses as total. Serum activities of lactate dehydrogenase (LDH), creatine phosphokinase (CK) and aspartate transaminase (AST) were determined. Endogenous lipid peroxidation was assessed by measuring the levels of malondialdehyde (MDA) in heart homogenates. In vitro susceptibility of tissues to oxidative stress was assessed by using two different media. Tissue glutathione (GSH) and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. All serum enzymatic activities were found markedly elevated in ethanol group. Binge ethanol administration significantly enhanced endogenous lipid peroxidation and caused an enhanced in vitro susceptibility to lipid peroxidation. Levels of reduced GSH and GSH-Px and GST activities were found unchanged as compared to controls. SOD activity was found significantly increased. As a conclusion, binge ethanol consumption which was applied to rats to investigate acute tissue injury, appeared to confirm the generation of oxidative stress in rat hearts.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

AT1-AA通过上调细胞自噬诱导大鼠心功能不全

目的:建立血管紧张素Ⅱ1型受体自身抗体(AT1-AA)主动免疫大鼠模型,观察AT1-AA对心肌细胞自噬和凋亡的影响,并探究其引起心功能不全的作用机制.方法:以人工合成的血管紧张素Ⅱ1型受体细胞外第二环肽段主动免疫建立大鼠模型;小动物超声仪检测心脏功能和结构变化;HE染色观察心脏结构变化;TUNEL染色检测心肌细胞凋亡情...     

松果体及褪黑素对大鼠胸腺CD4+/CD8+T细胞分化发育的影响

目的：探讨松果体和褪黑素对胸腺T细胞分化发育的影响。方法：实验组为松果体摘除组和松果体摘除 褪黑素组。ABC法染胸腺CD4^ 、CD8^ 细胞。流式细胞术测定胸腺和血液T淋巴细胞CD4^ 、CD8^ T亚类。结果：松果体摘除后胸腺明显萎缩,并随时间延长而加剧,补充褪黑素后胸腺重量逐渐恢复。松果体摘除后胸腺和血液中CD4^ T细胞百分比无明显波动;胸腺CD8^ T细胞比例上升,但血液CD8^ T细胞比例则下降;补充褪黑素后胸腺CD4^ T细胞在低剂量组略有下降,而高剂量组则显著升高,胸腺和血液CD8^ T呈下降趋势,双阳性细胞比例恢复正常,双阴性细胞比例则上升。结论：松果体能显著影响CD8^ T细胞的分化发育和释放,降低血液CD8^ T细胞的比例。补充褪黑素能缓解相关影响。     

缺血预适应对青年与老年大鼠缺血/再灌注心肌氧化应激及线粒体功能的影响

目的:探讨缺血预适应(ischemic preconditioning,IPC)对青年与老年大鼠缺血/再灌注(ischemia/reperfusion,IR)心肌损伤的影响。方法:雄性3月龄(青年)与20月龄(老年)Wistar大鼠,应用离体心脏灌流方法复制心肌IR与IPC模型。实验分为青年缺血/再灌注(YIR)组、青年缺血预适应(YPC)组、老年缺血再灌注(OIR)组与老年缺血预适应(OPC)组。透射电镜观察心肌及心肌线粒体超微结构变化;TTC染色测定心肌梗死面积;比色法测定冠脉流出液中乳酸脱氢酶(LDH)活性、心肌组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;酶联免疫吸附法测定心肌组织硝基化与羰基化蛋白质含量,TUNEL方法检测心肌细胞凋亡;氧电极法测定线粒体呼吸功能及钙诱导的线粒体渗透性转运孔开放情况。结果:与YIR组比较,YPC组心肌梗死面积明显减少,冠脉流出液中LDH活性降低,心肌组织的SOD活性增加,MDA含量降低,心肌硝基化与羰基化蛋白含量降低。电镜下可见YPC组心肌及分离的心肌线粒体膜结构完整、基质致密。YIR组心肌线粒体呼吸控制率与Ⅲ态耗氧量及P/O比值均明显增加,质子漏出减少,钙诱导的线粒体肿胀明显减轻,心肌细胞凋亡率下降。而与OIR组比较,OPC组上述指标均无显著统计学差异。与YPC组比较,OPC组心肌超微结构损伤明显增加,心肌氧化应激水平增加,线粒体呼吸功能下降,心肌细胞凋亡与坏死增多。结论:缺血预适应能够保护青年大鼠心肌缺血/再灌注损伤;而老年大鼠心脏对预适应刺激减敏,导致缺血预适应心肌保护作用钝化,这可能与老龄IPC心脏氧化应激水平增加导致线粒体损伤、细胞凋亡有关。     

褪黑激素对老年大鼠肝MDA含量和GSH—px、CAT，Ca^2＋—ATPase活性的影响

为探讨褪黑激素保肝抗衰老的作用及其机理 ,文章观察了褪黑激素对老年大鼠肝过氧化脂质产物含量和氧自由基、细胞内钙离子清除能力的影响。连续 30天给初老大鼠补充褪黑激素后 ,用生化比色法测定了肝组织内丙二醛 (MDA)含量和谷胱甘肽过氧化物酶 (GSH- px) )、氢过氧化物酶(CAT)、钙离子 -三磷酸腺苷酶 (Ca2 - ATPase)活性。与对照组比较 ,实验组大鼠肝内 MDA含量下降了 31.2 % ,GSH- px、CAT和 Ca2 - ATPase活性分别提高了 2 5.1%、49.6%和 2 5.4%。提示 ,褪黑激素能增强肝细胞抗氧化能力和清除细胞内游离钙离子的能力 ,具有一定的保护肝细胞和抗衰老作用。     

Pineal involvement in the alimentary behavior and taste preferences in the rat

The purpose of this experiment was to explore the effects of pinealectomy or sham pinealectomy on circadian rhythms of taste preferences, food and fluid intake and body weight gain in rats. We compared the body weight gain, the amounts of food eaten and that of deionized water, total fluid, salt, sour, sweet and bitter near-threshold solutions consumed by rats before all surgical manipulations and after pinealectomy or sham pinealectomy. The results showed that the pineal gland does not exert a major influence on circadian organization of taste preferences, drinking, feeding and body weight modifications in the rat. The failure of pinealectomy to modify light/dark rhythms of taste preferences and other related alimentary behaviors may be explained by the fact that pinealectomy does not completely eliminate circulating melatonin.     

Pinealectomy ameliorates collagen II-induced arthritis in mice.

To extend our previous findings that exposure to constant darkness (stimulation of endogenous melatonin release) as well as treatment with exogenous melatonin magnifies the severity of collagen-induced arthritis in mice, we have examined the effects of melatonin cutback by removing the pineal gland. Two strains of mice, DBA/1 and NFR/N, were subjected to surgical pinealectomy. The melatonin levels in sera were reduced by approximately 70% by the pinealectomy compared with the corresponding sham-operated controls. After 3-4 weeks of rest the mice were immunized with rat type II collagen to induce autoimmune arthritis, and the animals were kept in constant darkness during the experiments. In comparison with the controls, all groups of pinealectomized mice showed reduced severity of the arthritis by means of (i) a slower onset of the disease, (ii) a less severe course of the disease (reduced clinical scores), and (iii) reduced serum levels of anti-collagen II antibodies. These effects were not significant in all experiments, but the trends were always the same. Thus, the present result strengthen the hypothesis that high physiological levels of melatonin (which can be induced by exposure to darkness) stimulate the immune system and cause exacerbation of autoimmune collagen II arthritis, while inhibition of melatonin release (pinealectomy or exposure to light) has a beneficial effect.     

二氧化硫对大鼠缺血再灌注心脏的损伤作用

目的观察二氧化硫(SO2)在心肌缺血再灌注损伤中的作用。方法大鼠心脏分为:I/R组,SO2组及天冬氨酸异羟肟酸(HDX)组。采用Langendorff离体心脏灌注模型。MacLab数据采集系统监测离体心脏功能。结果SO2组心功能恢复率明显低于I/R组(P<0.05,P<0.01);HDX组显著高于I/R组(P<0.05,P<0.01)。SO2组冠脉流液中乳酸脱氢酶(LDH)、肌酸激酶(CK)、谷氨酸-草酰乙酸转移酶(GOT)活性、肌红蛋白(Mb)含量及心肌丙二醛(MDA)、共轭双烯键(CD)含量及GOT活性显著高于I/R组(P<0.05,P<0.01);HDX组冠脉流液中上述指标明显低于I/R组(P<0.05,P<0.01)。SO2组心肌还原型谷胱甘肽(GSH)含量明显低于I/R组(P<0.05);HDX组心肌GSH含量显著高于I/R组(P<0.01)。结论SO2参与了大鼠心肌缺血再灌注损伤。增加心肌脂质过氧化及降低心肌还原型谷胱甘肽含量可能与SO2心肌损伤有关。     

多肽化合物urantide抑制动脉粥样硬化大鼠心脏Ⅰ型胶原的表达

目的 观察多肽类化合物urantide对动脉粥样硬化（As）大鼠心脏组织中Ⅰ型胶原（ColⅠ）表达的影响,探讨其防治损伤的作用机制。方法 选取健康雄性3周龄SPF级Wistar大鼠60只,采用腹腔注射维生素D3（VD3）损伤动脉内膜及高脂饲料饲养的方法建立大鼠As模型,随机分为：正常组、As模型组、辛伐他汀组和urantide（3 d、7 d、14 d）组。采用HE染色和Masson三色染色方法,观察大鼠心脏组织形态和胶原纤维表达,免疫组织化学、Western blotting和Real-time PCR方法检测大鼠心脏Col Ⅰ蛋白和基因的表达。结果 与正常组相比,As模型组大鼠心脏组织中出现心肌细胞变性,细胞间浸润大量的中性粒细胞,且有散布的泡沫细胞及充血出血等病理现象,同时胶原纤维增加,ColⅠ的基因和蛋白表达水平升高。与As模型组相比,经urantide治疗后心脏病理现象有缓解。随着给药时间的延长,胶原纤维减少,ColⅠ的基因和蛋白表达水平逐渐下调,尤以给药14 d时效果最佳。 结论 Urantide可抑制As大鼠心脏组织ColⅠ表达以缓解心肌间质损伤,对As大鼠的心脏具有保护作用。     

褪黑激素对老年大鼠肾MDA含量和GSH—px、CAT、Ca^2＋—ATPase活性的影响

为探讨褪黑激素在抗肾老化的作用及机理，观察了褪黑激素对老年大鼠肾过氧化脂质产物的含量及对氧自由基与细胞内钙离子清除能力的影响。本实验连续３０ 天给初老大鼠补充褪黑激素，采用生化比色法测定了肾组织内丙二醛（ＭＤＡ）含量和谷胱甘肽过氧化物酶（ＧＳＨｐｘ）、氢过氧化物酶（ＣＡＴ）与钙离子三磷酸腺苷酶（Ｃａ２＋ ＡＴＰａｓｅ）活性。与对照组比较，实验组大鼠肾组织ＭＤＡ 含量下降了１２７％ ，而ＧＳＨｐｘ、ＣＡＴ 和Ｃａ２＋ ＡＴＰａｓｅ 活性则分别提高了２７５％ 、２９５％ 和３９８％ 。提示　褪黑激素能增强肾抗氧化能力和清除游离钙离子的能力，对延缓肾结构老化和肾功能减退具有一定的作用     

松果体褪黑素对大鼠胸腺CD4~+ CD25~+调节性T细胞发育及其相关基因Foxp3的影响

目的研究松果体摘除及补充褪黑素对大鼠胸腺CD4+ CD25+调节性T细胞(Treg细胞)产生、输出及其相关基因叉状头/翅膀状螺旋转录子(Foxp3)表达的影响。方法选用雄性清洁级SD大鼠120只,分为正常组、假手术组、松果体摘除组、松果体摘除+褪黑素低剂量组[腹腔注射7.5mg/(kg·d)]和松果体摘除+褪黑素高剂量组[腹腔注射15mg/(kg·d)],术后4、8周取材。应用流式细胞检测技术、RT-PCR法及免疫组织化学染色法观察并分析松果体摘除及补充外源性褪黑素后胸腺及外周血CD4、CD25双阳性细胞数量及胸腺Foxp3表达的变化。结果松果体摘除术后无论4周或者8周胸腺CD4+ CD25+ Treg细胞数量均无明显变化,补充褪黑素后双阳性细胞数量呈时间、剂量依赖性明显增加;松果体摘除术后4周外周血CD4+ CD25+ Treg细胞数量明显增加,但补充褪黑素后恢复正常,而术后8周各组之间无显著性差异;半定量RT-PCR及免疫组织化学结果显示,松果体摘除后4周大鼠胸腺Foxp3表达水平明显升高,补充高低两种剂量褪黑素后均有所下降并达到正常水平,而松果体摘除后8周各组之间Foxp3的表达无明显差异。结论松果体摘除对胸腺CD4+ CD25+ Treg细胞的产生无明显影响,但导致大鼠胸腺Foxp3的转录和翻译明显增加,胸腺CD4+ CD25+ Treg细胞的输出增加,而补充外源性褪黑素后能逆转上述异常,长时间作用则其影响逐渐消失。     

Not Only Melatonin but also Caffeic Acid Phenethyl Ester Protects Kidneys against Aging-related Oxidative Damage in Sprague Dawley Rats

Microscopic features and antioxidant status of kidneys of young, old, and caffeic acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats were evaluated. Aging-related tubular and glomerular changes were evident. The most prominent tubular alterations were massive vacuole formation, mitochondrial degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001), and glutathione peroxidase (GPx) activities (p < .05), and total glutathione (GSH) level were decreased in old animals. Melatonin significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean tissue MDA levels of melatonin and CAPE-administered rats were even lower than those of young rats (p < .05). In conclusion, tubular and glomerular structures and tissue antioxidant enzyme activities were very well preserved in CAPE and melatonin-administered rats.     

Melatonin modulates cytoskeletal organization in the rat brain hippocampus

Melatonin concentration in plasma reaches high levels during the night and synchronizes body rhythms with the photoperiod. Previous evidence obtained in cultured cells suggests that melatonin synchronizes cytoskeletal re-arrangements at nocturnal plasma concentration. In this study, we determined the amount of microtubules and microfilaments in the rat hippocampus as an index of cytoskeletal organization in rats submitted to a photoperiodic regime. Additionally, these parameters were determined in control rats, sham rats, pinealectomized rats, and rats that were pinealectomized and treated with melatonin for 1 week. The results showed an increase in both the amount of microfilaments in the hippocampus of rats sacrificed in the dark phase, and in melatonin levels. In addition, a decrease in both microfilament and microtubule amounts occurred in pinealectomized rats. In contrast, melatonin treatment partially reestablished actin and tubulin proportions organized in microfilaments and microtubules, respectively. The results indicate that actin organization in microfilaments was associated with both the photoperiod and with melatonin levels. Together, the data support that cytoskeletal organization is regulated rhythmically by melatonin in synchrony with the photoperiod.     

Pinealectomy causes hippocampal CA1 and CA3 cell loss: reversal by melatonin supplementation

This experiment determined if the loss of endogenous melatonin via pinealectomy affected rat CA1 and CA3 pyramidal neuron numbers over a 20-month span. Since pinealectomy eliminates many neurohormones, some rats received daily melatonin supplementation to determine if this would reverse its effects. CA1 pyramidal cells were significantly reduced between 2 and 4 months after pinealectomy. CA3 loss was evident at 2 months post-pinealectomy. Melatonin replacement in the drinking water prevented these effects and seemingly promoted the genesis of CA1 cells. Analyses of hippocampal thiobarbituric acid reactive substances (TBARS) levels at 3 and 20 months post-surgery, revealed no significant group differences in lipid peroxidation. However, hippocampal TBARS were higher at 20 than at 3 months in all groups. Pinealectomized rats exhibited a significantly higher ratio of reduced to oxidized glutathione at 3 months but not 20 months, when compared to the sham and melatonin-supplemented rats. This suggests that pinealectomy caused oxidative stress and a subsequent compensatory change in the glutathione system. These results indicate that endogenous melatonin is neuroprotective.