Glycine Provokes Lipid Oxidative Damage and Reduces the Antioxidant Defenses in Brain Cortex of Young Rats

Patients affected by nonketotic hyperglycinemia (NKH) usually present severe neurological symptoms and suffer from acute episodes of intractable seizures with leukoencephalopathy. Although excitotoxicity seems to be involved in the brain damage of NKH, the mechanisms underlying the neuropathology of this disease are not fully established. The objective of the present study was to investigate the in vitro effects of glycine (GLY), that accumulate at high concentrations in the brain of patients affected by this disorder, on important parameters of oxidative stress, such as lipid peroxidation (thiobarbituric acid-reactive substances (TBA-RS) and chemiluminescence) and the most important non-enzymatic antioxidant defense reduced glutathione (GSH) in cerebral cortex from 30-day-old rats. GLY significantly increased TBA-RS and chemiluminescence values, indicating that this metabolite provokes lipid oxidative damage. Furthermore, the addition of high doses of the antioxidants melatonin, trolox (soluble vitamin E) and GSH fully prevented GLY-induced increase of lipid peroxidation, indicating that free radicals were involved in this effect. GLY also decreased GSH brain concentrations, which was totally blocked by melatonin treatment. Finally, GLY significantly reduced sulfhydryl group content from a commercial GSH solution, but did not oxidize reduced cytochrome C. Our data indicate that oxidative stress elicited in vitro by GLY may possibly contribute at least in part to the pathophysiology of the neurological dysfunction in NKH.     

Increased Receptor for Advanced Glycation Endproducts Immunocontent in the Cerebral Cortex of Vitamin A-Treated Rats

Vitamin A, beyond its biological role, is an alternative choice in treating some life threatening pathologies, for instance leukemia and immunodeficiency. On the other hand, vitamin A therapy at moderate to high doses has caused concern among public health researchers due to the toxicological aspect resulting from such habit. It has been described hepatotoxicity, cognitive disturbances and increased mortality rates among subjects ingesting increased levels of vitamin A daily. Then, based on the previously reported data, we investigated here receptor for advanced glycation endproducts (RAGE) immunocontent and oxidative damage levels in cerebral cortex of vitamin A-treated rats at clinical doses (1,000–9,000 IU/kg day⁻¹). RAGE immunocontent, as well as oxidative damage levels, were observed increased in cerebral cortex of vitamin A-treated rats. Whether increased RAGE levels exert negative effects during vitamin A supplementation it remains to be investigated, but it is very likely that deleterious consequences may arise from such alteration.     

Topiramate and Vitamin E Modulate the Electroencephalographic Records,Brain Microsomal and Blood Antioxidant Redox System in Pentylentetrazol-Induced Seizure of Rats

We investigated the effects of vitamin E and topiramate (TPM) administrations on pentylentetrazol (PTZ)–induced blood and brain toxicity in rats. Forty rats were randomly divided into five equal groups. The first and second groups were used for the control and PTZ groups, respectively. Fifty or 100 mg TPM were administered to rats constituting the third and fourth groups for 7 days, respectively. The TPM and vitamin E combination was given to animals in the fifth group. At the end of 7 days, all groups except the first received a single dose of PTZ. Blood and brain samples were taken at 3 hrs after PTZ administration. Lipid peroxidation levels of plasma, erythrocyte, brain cortex and brain microsomal fraction; nitric oxide levels of serum; and the number of spikes and epileptiform discharges of the EEG were increased by PTZ administration. Plasma and brain vitamin E concentration, erythrocyte glutathione peroxidase (GSH-Px) activity and latency to first spike of the EEG were decreased by PTZ. Plasma lipid peroxidation levels in the third group and plasma and erythrocyte lipid peroxidation levels in the fifth group were decreased compared to the second group, whereas brain vitamin C, vitamin E, erythrocyte GSH-Px and reduced glutathione (GSH) values increased in the fifth group. Brain microsomal GSH levels and EEG records in the third, fourth and fifth groups were restored by the TPM and vitamin E treatment. In conclusion, TPM and vitamin E seems to have protective effects on PTZ-induced blood and brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.     

Acute and Chronic Hyperammonemia Modulate Antioxidant Enzymes Differently in Cerebral Cortex and Cerebellum

Studies on acute hyperammonemic models suggest a role of oxidative stress in neuropathology of ammonia toxicity. Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated functions. To understand whether cerebellum responds differently than other brain regions to chronic type HA with respect to oxidative stress, this article compares active levels of all the antioxidant enzymes vis a vis extent of oxidative damage in cerebral cortex and cerebellum of rats with acute and chronic HA induced by intra-peritoneal injection of ammonium acetate (successive doses of 10 × 10³ & 8 × 10³ μmol/kg b.w. at 30 min interval for acute and 8 × 10³ μmol/kg b.w. daily up to 3 days for chronic HA). As compared to the respective control sets, cerebral cortex of acute HA rats showed significant decline (P < 0.01–0.001) in the levels of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) but with no change in glutathione reductase (GR). In cerebellum of acute HA rats, SOD, catalase and GR though declined significantly, GPx level was found to be stable. Contrary to this, during chronic HA, levels of SOD, catalase and GPx increased significantly in cerebral cortex, however, with a significant decline in the levels of SOD and GPx in cerebellum. The results suggest that most of the antioxidant enzymes decline during acute HA in both the brain regions. However, chronic HA induces adaptive changes, with respect to the critical antioxidant enzymes, in cerebral cortex and renders cerebellum susceptible to the oxidative stress. This is supported by ∼ 2- and 3-times increases in the level of lipid peroxidation in cerebellum during chronic and acute HA respectively, however, with no change in the cortex due to chronic HA.     

Fulminant Hepatic Failure in Rats Induces Oxidative Stress Differentially in Cerebral Cortex,Cerebellum and Pons Medulla

Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat brain-cerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex. Murthy Ch.R.K—Deceased while in service.     

液压脑损伤大鼠大脑皮质突触素的动态变化

目的:探讨液压脑损伤后突触素在皮质区表达的动态变化.方法:应用液压脑损伤复制脑损伤动物模型,应用免疫组织化学和计算机图像分析技术定量分析皮质受损区突触素表达的动态变化.结果:突触素在皮质受伤区表达呈现两次高峰:分别为3～12h和15～30d,90d表达接近正常.结论:突触素在皮质受伤区第2次表达增高可能与脑的结构和功能恢复有关.急性期表达增高则可能与脑的直接损伤有关.     

幼年大鼠视皮层神经元对闪光刺激的反应特性

哺乳动物视觉系统的发育延续到出生后,大鼠出生后 3~5 周是视觉系统发育的关键期 . 在关键期中,视皮层的兴奋性和抑制性突触连接逐渐成熟,形成有效的皮层内回路 . 为了观察发育关键期大鼠视皮层神经元的反应特性与成年大鼠的异同,使用胞外单细胞记录的方法对比研究了幼年和成年大鼠对闪光刺激的视觉反应特性 . 结果显示：与成年大鼠相比较,幼年大鼠视皮层神经元对持续闪光刺激显示出更强的适应性,对光刺激的诱发放电频率更低,而在没有光刺激时的自发放电频率更高,从而导致信噪比更低 . 这一结果表明,幼年大鼠视皮层对连续刺激的反应能力下降,对信号的分辨能力也更弱,其原因可能是兴奋性突触和抑制性突触发育的不同步所致 .     

Brain most susceptible to cadmium induced oxidative stress in mice

Accumulated evidence over the years indicate that cadmium (Cd) may be a possible etiological factor for neurodegenerative diseases. This may possibly be linked to excessive generation of free radicals that damages the organs in the body depending on their defence mechanism. Since Cd is a toxic agent that affect several cell types, the aim of this study was to shed light on the effect of Cd and its consequences on different organs of the mice body. To test the hypothesis of concentration dependent Reactive Oxygen Species (ROS) generation and DNA damage, observations were done in the serum of 4–5 weeks old male Swiss albino mice by treating with cadmium chloride (CdCl₂) in drinking water for 30 days. The expression of Bcl-2-associated X protein (Bax) an apoptotic marker protein was two times higher in brain compared to liver at an exposure level of 0.5 mg L⁻¹ CdCl₂. Furthermore the correlation and linkage data analysis of antioxidant defence system revealed a rapid alteration in the brain, compared to any other organs considered in this study. We report that even at low dose of Cd, it impaired the brain due to lipid peroxidase sensitivity which favoured the Cd-induced oxidative injury in the brain.     

双酚A对雄性大鼠抗氧化能力影响的初步研究

目的：探讨双酚A（BPA）对成年大鼠抗氧化能力的影响。方法：将健康成年雄性SD大鼠84只随机分为5个双酚A染毒剂量组（200、50、5、0.5、0.0005 mg/kg）和1个对照组,连续灌胃染毒8周,并监测体重变化,染毒结束后测定血浆超氧化物歧化酶（SOD）和谷胱甘肽-过氧化物酶（GSH-Px）含量;此外,提取肝脏组织RNA,用荧光实时定量PCR测定肝脏硫氧还原蛋白过氧化物酶2（prdx2）mRNA的表达水平。结果：随着染毒时间的延长,50 mg/kg及200 mg/kg剂量组的动物体重增长速度逐渐减慢,自4周开始,与对照组相比有显著差异（P〈0.05）;染毒结束时,其体重分别为对照组的90.52%和91.61%（p〈0.05）,而其它低剂量组间则无明显差异;大鼠血浆GSH-Px含量总体上呈下降趋势,且5 mg/kg以上剂量组与对照组相比差别均有统计学意义（p〈0.01）;染毒组血浆SOD水平虽也低于对照组,但无统计显著性;此外,大鼠肝脏组织prdx2 mRNA水平随双酚A剂量增高呈剂量依赖性降低,与对照组相比,其在最低剂量组（0.0005 mg/kg）即有显著差异（p〈0.01）。结论：双酚A可造成大鼠抗氧化酶系统失衡,导致氧化损伤效应,prdx2可能是反映其氧化损伤敏感的生物学标志。     

右美托咪啶通过抑制线粒体功能障碍衍生的氧化应激保护宫内窘迫新生鼠的脑功能障碍的机制

摘要 目的：探讨右美托咪啶通过抑制线粒体功能障碍衍生的氧化应激保护宫内窘迫新生鼠的脑功能障碍的机制。方法：24周龄Sprague-Dawley大鼠,按照雌雄比= 1：2的饲养于笼中自然受孕,对确定受孕的大鼠进行宫内窘迫模型手术,然后分为对照组、宫内窘迫组和右美托咪啶组。通过莫里斯水迷宫测试测和牵引力测试分别检测大鼠的学习能力、运动能力。使用电子分析天平检测大鼠脑含水量,通过FJB染色确定退化神经元的数目。通过商购试剂盒检测大鼠氧化应激指标谷胱甘肽过氧化物酶（Glutathione peroxidase, GPx）、丙二醛（Malondialdehyde, MDA）和还原型辅酶Ⅱ（Nicotinamide adenine dinucleotide, NADPH）的含量。通过蛋白印迹分析Hsp90和p-AKT Thr 308的蛋白表达。通过RT-PCR分析线粒体介导的神经元凋亡相关因子caspase-3、Bax和Bcl-2的mRNA表达。结果：与对照组相比,宫内窘迫组迷宫测试用时、脑水含量、退化神经元量、MDA和NADPH含量以及caspase-3和Bax的mRNA表达均显著增加,牵引力得分、Hsp90和p-AKT Thr 308的蛋白表达以及Bcl-2mRNA表达均显著降低（P<0.05）,而与宫内窘迫组相比,右美托咪啶组迷宫测试用时、脑水含量、退化神经元量、MDA和NADPH含量以及caspase-3和Bax的mRNA表达均显著减少,牵引力得分、Hsp90和p-AKT Thr 308的蛋白表达以及Bcl-2mRNA表达均显著增加（P<0.05）。结论：右美托咪啶减轻了宫内窘迫大鼠的线粒体功能障碍,进而抑制了氧化应激并改善了大鼠的神经功能缺损和脑损伤。     

双酚A 对雄性大鼠抗氧化能力影响的初步研究

目的:探讨双酚A(BPA)对成年大鼠抗氧化能力的影响。方法:将健康成年雄性SD大鼠84只随机分为5个双酚A染毒剂量组(200、50、5、0.5、0.0005 mg/kg)和1个对照组,连续灌胃染毒8周,并监测体重变化,染毒结束后测定血浆超氧化物歧化酶(SOD)和谷胱甘肽-过氧化物酶(GSH-Px)含量;此外,提取肝脏组织RNA,用荧光实时定量PCR测定肝脏硫氧还原蛋白过氧化物酶2(prdx2)mRNA的表达水平。结果:随着染毒时间的延长,50 mg/kg及200 mg/kg剂量组的动物体重增长速度逐渐减慢,自4周开始,与对照组相比有显著差异(P<0.05);染毒结束时,其体重分别为对照组的90.52%和91.61%(p<0.05),而其它低剂量组间则无明显差异;大鼠血浆GSH-Px含量总体上呈下降趋势,且5 mg/kg以上剂量组与对照组相比差别均有统计学意义(p<0.01);染毒组血浆SOD水平虽也低于对照组,但无统计显著性;此外,大鼠肝脏组织prdx2 mRNA水平随双酚A剂量增高呈剂量依赖性降低,与对照组相比,其在最低剂量组(0.0005 mg/kg)即有显著差异(p<0.01)。结论:双酚A可造成大鼠抗氧化酶系统失衡,导致氧化损伤效应,prdx2可能是反映其氧化损伤敏感的生物学标志。     

Aging Diminishes Serotonin-Stimulated Arachdonic Acid Uptake and Cholinergic Receptor-Activated Arachidonic Acid Release in Rat Brain Cortex Membrane

Abstract: Synaptoneurosomal and synaptosomal fractions from the brain cortex of adult (4-month-old) and aged (27-month-old) rats were used for studies on the uptake and subsequent release of [¹⁴C]arachidonic acid ([¹⁴C]AA) from brain lipids. The incorporation of AA and the pattern of its uptake into lipids of the aged brain cortex synapto-neurosomes and synaptosomes were not significantly different when compared with those in the adult brain cortex fractions. Serotonin (5-HT), at 10 μM to 1 μM in the presence of pargyline and the agonist of the 5-HT_1A receptor, buspirone, stimulated AA uptake into membrane lipids, mainly into phosphatidylinositol, by about 40% exclusively in adult brain synaptoneurosomes. Aging significantly diminished the effect of 5-HT on AA uptake. Synaptoneurosomal and synaptosomal fractions prelabeled with [¹⁴C]AA were used subsequently for investigation of voltage-dependent, muscarinic and 5-HT receptor-mediated AA release. Aging diminished markedly carbachol-stimulated Ca²⁺-dependent AA liberation from membrane lipids of synaptoneurosomes and synaptosomes. Moreover, aging decreased voltage-dependent and 5-HT₂ receptor-mediated AA release. These results show that aging affects receptor-dependent AA uptake and pre-and postsynaptic receptor-mediated AA release. These modulations of AA incorporation and release in aged brain may be of patho-physiological significance, in view of the importance of these processes for signal transmission in the brain. The changes of receptor-dependent processes of deacylation and reacylation may be responsible for alteration in the function of neuronal cells and may affect learning and memory ability and brain plasticity during aging.     

芸香苷对慢性脑低灌注大鼠认知功能障碍和脑损伤的神经保护作用

目的:研究芸香苷对慢性脑低灌注导致大鼠认知功能障碍和脑损伤的影响。方法:采用双侧颈总动脉结扎法(bilateral common carotid artery occlusion,BCCAO)建立慢性脑低灌注大鼠模型,随机分为4组(n=10):生理盐水治疗模型组、芸香苷治疗模型组、生理盐水治疗假手术组、芸香苷治疗假手术组;连续腹腔注射芸香苷和生理盐水共12周。采用Morris水迷宫评定大鼠学习和记忆能力。采用分光光度法检测脑组织中枢胆碱能相关指标和氧化应激指标。应用免疫组织化学和El ISA方法检测脑组织炎症反应。采用Nissl染色法检测脑组织神经元缺失。结果:芸香苷治疗模型组大鼠的逃脱潜伏期较生理盐水治疗模型组明显减少(P0.01)。与生理盐水治疗模型组相比,芸香苷治疗后显著提高了BCCAO大鼠脑组织中ACh水平(P0.01)和Ch AT活性(P0.01),并降低了ACh E活性(P0.01)。与生理盐水治疗模型组相比,芸香苷治疗模型组显著增加了大鼠脑组织中SOD活性(P0.01)和GPX活性(P0.01),降低了MDA水平(P0.01)和蛋白质羰基化合物水平(P0.01)。芸香苷治疗模型组大鼠海马区GFAP-免疫阳性星型胶质细胞(P0.01)和Iba1-免疫阳性小胶质细胞(P0.01)面积百分比较生理盐水治疗模型组显著减少。芸香苷治疗模型组大鼠海马区正常神经元的数量较生理盐水治疗模型组大鼠显著增加(P0.01)。结论:芸香苷可改善慢性脑低灌注引起的大鼠认知功能障碍和脑损伤。     

Age-related Oxidative Modifications of Proteins and Lipids in Rat Brain

Oxidants have been shown to play a major role in ageing and ageing-related neurodegenerative diseases. In the present study, we investigated the effect of ageing on oxidative damage to lipids and proteins in brain homogenate, mitochondria and synaptosomes of adult (6-month-old), old (15-month-old), and senescent (26-month-old) Wistar rats. There was a significant increase in thiobarbituric acid-reactive substances and conjugated dienes in homogenates, which indicate increased lipid peroxidation (LPO). Oxidative modifications of homogenate proteins were demonstrated by a loss of sulfhydryl content, accumulation of dityrosines and formation of protein conjugates with LPO-end products. Increase in protein conjugates with LPO-end products and a decrease in SH groups were observed also in mitochondria and synaptosomes, but dityrosine content was elevated only in synaptosomes. Protein surface hydrophobicity, measured by fluorescent probe 1-anilino-8-naphthalenesulfonate (ANS), was increased only in homogenate. These results suggest that besides mitochondria and synaptosomes other cellular compartments are oxidatively modified during brain ageing.     

Cysteamine Oxygenase: Possible Involvement of Superoxide Ion in the Catalytic Mechanism

The reaction catalyzed by cysteamine oxygenase on cysteamine in the presence of phenazine methosulphate as cofactor like compound is inhibited by nitroblue tetrazolium, a scavenger of superoxide ions. The reaction is not inhibited by superoxide dismutase and allyl alcohol and it is not activated by superoxide ions produced in solution. Nitroblue tetrazolium is reduced by cysteamine or mercaptoethanol and phenazine methosulphate. This reaction is completely inhibited by superoxide dismutase. In the presence of cysteamine oxygenase the reduction with mercaptoethanol is greatly enhanced and it is only partially inhibited by superoxide dismutase. According to these data a reaction mechanism is proposed in which superoxide ions and thiyl radicals are produced at the active site during catalysis.     

Fos Immunoreactivity and NADPH-d Reactivity in the Brain Cortex of Rats Realizing Motivated Stereotyped Movements by the Forelimb

A comparative study of mmunoreactivity with respect to c-Fos protein in the motor (zones М1 and М2), medial prefrontal (PrL and IL), and cingular (Cg1 and Cg2) cortices allowed us to find significant differences between the intensities of expression of gene c-fos in these cortical regions in control rats (group 1) and animals trained to perform catching of food globules by the forelimb (i.e., realizing an operant food-procuring reflex, group 2). The density of distribution of Fos-immunoreactive (Fos-ir) neurons in rats of group 2 in motor and limbic cortical zones at +2.2 to +0.2 levels rostrally from the bregma were significantly lower than in control rats (Р < 0.05). In animals of group 2, we also found significantly greater numbers of Fos-ir neurons in the contralateral (with respect to the active extremity) zones of the cortex at all examined levels. These changes are probably related to functional changes in the cortex resulting from learning of motor habits in the course of training sessions for stabilization of the operant reflex. Histochemical estimation of the NADPH-diaphorase (NADPH-d) activity in the motor and limbic cortex showed that, in rats of both groups, the maximum number of labeled interneurons per slice in the М1 zone were observed in layers II/III, V, and VI (5.6 ± 0.4, 6.4 ± 0.5, and 14.0 ± 0.8, respectively, within 200 × 200 μm₂ areas). In the limbic cortex, NADPH-d-reactive (NADPH-d-r) interneurons were also met in layers II/III, V, and VI. Cortical NADPHd-r neurons with the Fos-ir nuclei were not found. The presence of spatial associations of the somata or processes of NADPH-d-r neurons with intraparenchimal arterioles and microvessels was a typical feature of the distribution of NADPH-d-reactivity in the М1 and М2 zones, as well as in Cg1, Cg2, PrL, and IL. The following succession of the density of neurovascular associations was observed: Cg1 > Cg2 > М1 > М2 > > PrL. As is supposed, NADPH-d-r neurons (i.e., cells generating NO) are involved in the control of regional blood flow in the studied cortical regions. Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 348–358, July–August, 2008.     

Thyroid Hormone Influences Antioxidant Defense System in Adult Rat Brain

The objective of the current study was to find out whether thyroid hormone influences antioxidant defense parameters of rat brain. Several oxidative stress and antioxidant defense parameters of mitochondrial (MF) and post-mitochondrial (PMF) fractions of cerebral cortex (CC) of adult rats were compared among euthyroid (control), hypothyroid [6-n-propylthiouracil (PTU)-challenged], and hyperthyroid (T3-treatment to PTU-challenged rats) states. Oxidative stress parameters, such as thiobarbituric acid-reactive substances (TBA-RS) and protein carbonyl content (PC), in MF declined following PTU challenge in comparison to euthyroid rats. On the other hand, when PTU-challenged rats were treated with T3, a significant increase in the level of oxidative stress parameters in MF was recorded. Hydrogen peroxide content of MF as well as PMF of CC was elevated by PTU-challenge and brought to normal level by subsequent treatment of T3. Although mitochondrial glutathione (reduced or oxidized) status did not change following PTU challenge, a significant reduction in oxidized glutathione (GSSG) level was noticed in PMF following the treatment. T3 administration to PTU-challenged rats had no effect on mitochondrial glutathione status. Total and CN-resistant superoxide dismutase (SOD) activities in MF of CC augmented following PTU challenge. CN-resistant SOD activity did not change when PTU-challenged rats were treated with T3. Although CN-sensitive SOD activity of PMF remained unaltered in response to PTU challenge, its activity increased when PTU-challenged rats were treated with T3. Catalase activity in PMF of CC of PTU-challenged rats increased, whereas the activity was decreased when hypothyroid rats were treated with T3. Similarly, total and Se-dependent glutathione peroxidase (GPx) activities of MF increased following PTU challenge and reduced following administration of T3. Se-independent GPx activity of MF and PMF and glutathione reductase activity of PMF decreased following PTU challenge and did not change further when rats were treated with T3. On the other hand, glutathione S-transferase activity of MF and PMF of CC did not change following PTU challenge but decreased below detectable level following T3 treatment. Results of the current investigation suggest that antioxidant defense parameters of adult rat brain are considerably influenced by thyroid states of the body.     

Effect of Mobile Phone Exposure on Apoptotic Glial Cells and Status of Oxidative Stress in Rat Brain

The aim of this study was to investigate the effects of mobile phone exposure on glial cells in brain. The study carried out on 31 Wistar Albino adult male rats. The rat heads in a carousel exposed to 900 MHz microwave. For the study group (n:14), rats exposed to the radiation 2h per day (7 days in a week) for 10 months. For the sham group (n:7), rats were placed into the carousel and the same procedure was applied except that the generator was turned off. For the cage control (n:10), nothing applied to rats in this group. In this study, rats were euthanized after 10 months of exposure periods and brains were removed.

Brain tissues were immunohistochemically stained for the active (cleaved) caspase-3, which is a well-known apoptosis marker, and p53. The expression of the proteins was evaluated by a semi-quantitative scoring system. However, total antioxidative capacity (TAC), catalase, total oxidant status (TOS), and oxidative stress index were measured in rat brain.

Final score for apoptosis in the exposed group was significantly lower than the sham (p < 0.001) and the cage control groups (p < 0.01). p53 was not significantly changed by the exposure (p > 0.05). The total antioxidant capacity and catalase in the experimental group was found higher than that in the sham group (p < 0.001, p < 0.05). In terms of the TOS and oxidative stress index, there was no statistically significant difference between exposure and sham groups (p > 0.05).

In conclusion, the final score for apoptosis, total antioxidant capacity and catalase in rat brain might be altered by 900 MHz radiation produced by a generator to represent exposure of global systems for mobile communication (GSM) cellular phones.     

Interactions Between Chronic Stress and Chronic Consumption of Caffeine on the Enzymatic Antioxidant System

We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.     

Effect of Brain Ischemia on Protein Kinase C

We examined the influence of brain ischemia on the activity and subcellular distribution of protein kinase C (PKC). Two different models of ischemic brain injury were used: postdecapitative ischemia in rat forebrain and transient (6-min) cerebral ischemia in gerbil hippocampus. In the rat forebrain model, at 5 and 15 min postdecapitation there was a steady decrease of total PKC activity to 60% of control values. This decrease occurred without changes in the proportion of the particulate to the soluble enzyme pools. Isolated rat brain membranes also exhibited a concomitant decrease of [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding with an apparent increase of the ligand affinity to the postischemic membranes. On the other hand, the ischemic gerbil hippocampus model displayed a 40% decrease of total PKC activity, which was accompanied by a relative increase of PKC activity in its membrane-bound form. This resulted in an increase in the membrane/total activity ratio, indicating a possible enzyme translocation from cytosol to the membranes after ischemia. Moreover, after 1 day of recovery, a statistically significant enhancement of membrane-bound PKC activity resulted in a further increase of its relative activity up to 162% of control values. In vitro experiments using a synaptoneurosomal particulate fraction were performed to clarify the mechanism of the rapid PKC inhibition observed in cerebral tissue after ischemia. These experiments showed a progressive, Ca(2+)-dependent, antiprotease-insensitive down-regulation of PKC during incubation. This down-regulation was significantly enhanced by prior phorbol (PDBu) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)