SIMILAR EFFECTS OF AGING AND PINEALECTOMY ON RAT BRAIN

随着年龄增长松果体功能受损，导致松果体功能不足。 褪黑激素从这个腺体分泌的褪黑激素。因此， 给老年人服用褪黑素被认为是一种 与衰老相关的昼夜节律丧失的治疗。或用于 神经内分泌和免疫失衡。褪黑素的缺乏及其作用 老年人的抗氧化活性可能在 衰老相关神经退行性脑疾病的病理生理学。 褪黑素可能影响抑制性神经递质的受体 γ-氨基丁酸(GABA)；这些受体的表达是 受衰老的影响。我们和其他人已经证明，褪黑素可以保护 对抗兴奋性神经递质谷氨酸的神经毒性作用， 尤其是当海人酸敏感型谷氨酸受体被刺激时。 我们发现，给大鼠服用褪黑素可以减弱海人藻酸- 诱发脑损伤，且在老年患者中，海人酸后损伤更大 成年动物。这种损害在松果体切除组也比在松果体切除组大 假手术大鼠。此外，我们发现摘除松果体会降低 GABAA受体复合体α1亚单位的mRNA表达。 其他人则报道了alpha1受体亚单位的表达减少。 老年大鼠的基因表达。我们假设褪黑激素缺乏 随着年龄的增长而发生，是GABAA表达变化的原因 受体亚基，增加的神经毒性海人酸兴奋性毒性，以及 改变苯二氮类药物(BZD)的抗兴奋性毒性作用。我们建议 以下目标：目标1：检验衰老和 松果体摘除(PIN-X)类似地增强红藻氨酸触发的海马区 损伤，外源性褪黑素具有神经保护作用 在老年和PIN-X大鼠中都是如此；目的2：检验衰老和 PIN-X类似地影响脑内GABA受体亚单位mRNAs的含量。 大鼠脑内PIN-X的作用可被褪黑素逆转 3：检验抗惊厥/神经保护作用的假设 抗红藻氨酸的BZD的作用也同样受到老化和半衰期的影响。 建议的项目是我们以前工作的合乎逻辑的延伸到 老龄化领域。我们将获得的结果可能有助于指导治疗 应对与衰老相关的神经退行性疾病的策略 这些疾病的老化部分，而不是针对特定疾病 机械装置。

The impairment of pineal function with age results in insufficient secretion of the hormone melatonin from this gland. Thus, the administration of melatonin to the elderly has been considered as a treatment for the aging-associated loss of circadian rhythms. Or for neuroendocrine and immune imbalances. The lack of melatonin and its antioxidative activity in the elderly might be important in the pathophysiology of aging-associated neurodegenerative brain disorders. Melatonin may influence the receptors for the inhibitory neurotransmitter gamma aminobutyric acid (GABA); the expression of these receptors is affected by aging. We and others have shown that melatonin protects against neurotoxic effects of the excitatory neurotransmitter glutamate, in particular when kainate-sensitive glutamate receptors are stimulated. We found that administration of melatonin to rats attenuates kainate- induced brain damage, and that greater damage occurs after kainate in old adult animals. This damage is also greater in pinealectomized than in sham-operated rats. In addition, we found that pinealectomy decreases the expression of mRNA for the alpha1 subunit of the GABAA receptor complex. Others have reported a decreased expression of alpha1 receptor subunit mRNA in old rats. We hypothesize that the melatonin deficiency that occurs with aging is responsible for changes in the expression of GABAA receptor subunits, increased neurotoxic kainate excitotoxicity, and for a changed antiexcitotoxic efficacy of benzodiazepines (BZDs). We propose the following AIMs: AIM 1: testing the hypothesis that aging and pinealectomy (PIN-X) similarly potentiate kainate-triggered hippocampal damage, and that administration of exogenous melatonin is neuroprotective both in old and PIN-X rats; AIM 2: testing the hypothesis that aging and PIN-X similarly affect the content of GABA receptor subunits mRNAs in the rat brain and that the effect of PIN-X can be reversed by melatonin; AIM 3: Testing the hypothesis that the anticonvulsive/neuroprotective action of BZDs against kainate is similarly affected by aging and pinalectory. The project proposed is a logical extension of our previous work into the area of aging. The results we will obtain might help to direct treatment strategies for neurodegenerative diseases associated with aging toward the aging component of these disorders, rather than at disease-specific mechanisms.