MONOAMINERGIC NEURAL TRANSPLANTS IN DEPRESSION

情绪障碍是最常见和最令人衰弱的 精神障碍。有很大比例的重大疾病患者 抑郁症会出现慢性或反复发作的症状。的成本 无论是从人的角度还是从经济角度来看，大萧条都是巨大的。虽然目前 现有的抗抑郁疗法在许多情况下都有效，它们是 受限于潜在的严重副作用，患者依从性差，以及 故意服药过量。 临床抑郁症很可能与一种精神错乱和失衡有关 中枢单胺能系统的功能。一种新的方法来解决 恢复中枢神经系统不平衡的功能是使用神经 移植。当神经移植物被放置在适当的区域时，可以 作为长期和容易获得的神经活性来源 物质。这种方法的一个显著优势是，对于慢性 抑郁症患者会有能力提供一个不断再生的 长期或永久的单胺来源，减少或 消除了反复服用抗抑郁药的需要。这个 提出的研究是评估神经的潜力的初步尝试。 通过移植来缓解抑郁。 评估单胺生产细胞移植到 缓解抑郁，将使用两个成熟的动物模型 最初；习得性无助模型和行为绝望 模特。习得的无助模式是研究得最多的，也是 临床抑郁症和抑郁症之间的许多相似之处支持 实验室观察，包括体重减轻、嗜睡和减少 动机，以及在生化和治疗方面的相似之处。这个 行为绝望模型特别敏感，因为它是一种 临床抗抑郁药。 单胺能移植物来源将包括松果体，它产生 高水平的5-羟色胺和肾上腺髓质，它产生高水平的 去甲肾上腺素水平。固体组织、外植体和细胞悬液 将接受测试以确定是否有能力减少测试中的行为缺陷 抑郁症模型。最初，移植物将被放置在 额叶新皮质，因为这个部位已经牵涉到人类 抑郁症，以及在动物抑郁症模型中。从长远来看 神经移植减少行为抑郁的潜力将是 随着时间的推移进行评估，从一周到一年不等。特定拮抗剂 将被用来评估从空气中释放的物质的贡献 移植到减少行为抑郁。这是一种 神经移植减少神经毒素注射后的缺陷 也将接受测试。移植物的活性和功能将被确定 随着时间的推移，使用生化分析和免疫细胞化学。

Disturbances of mood are among the most common and most debilitating of psychiatric disorders. A large proportion of patients with major depressive disorders suffer chronic or recurrent symptoms. The cost of depression is great, both in human and economic terms. While currently available antidepressant therapies are effective in many cases, they are limited by potentially serious side effects, poor patient compliance, and intentional overdose. Clinical depression most likely involves a disturbed and imbalanced functioning of CNS monoaminergic systems. A novel approach towards restoring imbalanced functioning in the CNS is the use of neural transplantation. When placed in appropriate regions, neural grafts can serve as a long-term and readily available source of neuroactive substances. A significant advantage of this approach for the chronically depressed patient would be the ability to provide a continually renewable source of monoamines on a long-term or permanent basis, reducing or eliminating the need for repeated antidepressant administration. The proposed study is an initial attempt to assess the potential for neural transplants to alleviate depression. To assess the potential for transplants of monoamine-producing cells to alleviate depression, two well established animals models will be used initially; the learned helplessness model and the behavioral despair model. The learned helplessness model is the best studied and is supported by a number of parallels between clinical depression and laboratory observations, including weight loss, lethargy, and reduced motivation, as well as similarities in biochemistry and treatment. The behavioral despair model is particularly sensitive as a screen for clinical antidepressants. Monoaminergic graft sources will include the pineal gland, which produces high levels of serotonin, and the adrenal medulla, which produces high levels of norepinephrine. Solid tissue, explants, and cell suspensions will be tested for ability to reduce behavioral deficits in the ra t depression models. Initially the transplants will be placed in the frontal neocortex, since this site has been implicated in human depression, as well as in animal depression models. The long term potential for neural transplants to reduce behavioral depression will be assessed over time, ranging from 1 week to 1 year. Specific antagonists will be used to assess the contribution of substances released from the grafts to the reduction of behavioral depression. The ability for the neural transplants to reduce deficits following neurotoxin administration will also be tested. Graft viability and function will be determined over time using biochemical assays and immunocytochemistry.