SEROTONIN REGULATION OF BASAL GANGLIA NEUROPEPTIDES

这项研究将确定5-羟色胺传输在 基底神经节神经肽基因表达的调控。 具体来说，我们将测试假设： 提供对神经肽nMRA表达的调控， 基底神经节通过多种受体亚型。 虽然这一规定 在正常条件下，可能仅对基因表达提供轻微的调节， 在成人大脑中，血清素可能会产生更大的影响， 在发育过程中，对多巴胺耗竭的反应，或在 谷氨酸引起的兴奋性毒性损伤 以下具体目标将 确定： 1. 5-羟色胺受体介导的基因表达调控 正常成人基底神经节。 多种血清素受体亚型可能 差异地影响基底神经节中的基因表达。 北方 分析和原位杂交方法将用于确定 哪些血清素受体与转录调控有关 前速激肽原和前脑啡肽原基因在纹状体中表达。 2. 5-羟色胺对脑缺血再灌注损伤基底节基因表达的影响 发展5-羟色胺传入前脑出现早， 并被假定在脑的形态发生中起作用 成熟 在胚胎期和出生后早期， 传输将被改变，特定的受体亚型将被 确定了影响神经肽基因表达的发育 基底神经节的模式 3. 5-羟色胺对脑缺血后基底节基因表达的影响 多巴胺传输。 5-羟色胺可能会增加其对基础 神经节基因表达对多巴胺改变的反应 神经传递 因此，实验将确定 5-羟色胺及其受体调节神经肽基因表达 在新生儿和新生儿中， 成人大脑 4. 5-羟色胺影响谷氨酸代谢过程中基因表达的机制 基底神经节的神经传递和兴奋性毒性损伤。 血清素 可能调节谷氨酸兴奋性神经传递的影响， 基底神经节，以及介导谷氨酸受体诱导 兴奋性毒性 实验将确定血清素如何有助于 基底神经节基因表达的调控 谷氨酸受体刺激 完成这些研究将增加我们对如何 5-羟色胺传递影响正常人的基因表达模式 发育和成年基底神经节;以及对 多巴胺和谷氨酸神经传递。 这些信息将增加 我们意识到血清素是基底神经节的主要传入调节器 发挥作用，并导致开发了基于降钙素的治疗方法， 治疗基底神经节疾病。

This research will determine the role of serotonin transmission in the regulation of neuropeptide gene expression in the basal ganglia. Specifically, we will test hypothesis that: Serotonin transmission provides regulatory control over neuropeptide nMRA expression within the basal ganglia via multiple receptor subtypes. Although this regulation may only provide slight adjustments to gene expression under normal conditions in the adult brain, serotonin may exert larger influences during development, in response to dopamine depletion, or during glutamate-induced excitotoxic damage. The following specific aims will determine: 1. Serotonin Receptor-Mediated Regulation of Gene Expression in the Normal Adult Basal Ganglia. Multiple serotonin receptors subtypes may differentially influence gene expression in the basal ganglia. Northern analysis and in situ hybridization methods will be utilized to determine which serotonin receptors are linked to transcriptional regulation of preprotachykinin and preproenkephalin genes expressed in the striatum. 2. Serotonin Influences on Basal Ganglia Gene Expression during Development. Serotonin afferent to the forebrain appear early during development and have been postulated to play a morphogenic role in brain maturation. During embryonic and early postnatal time periods, serotonin transmission will be altered and specific receptors subtypes will be identified that influence the development of neuropeptide gene expression patterns in the basal ganglia. 3. Serotonin Influences on Basal Ganglia Gene Expression during Altered Dopamine Transmission. Serotonin may increase its influence on basal ganglia gene expression in response to altered dopamine neurotransmission. Therefore, experiments will determine the role of serotonin and its receptors in regulating neuropeptide gene expression following manipulation of dopamine neurotransmission in both neonatal and adult brains. 4. Serotonin Mechanisms That Affect Gene Expression during Glutamate Neurotransmission and Excitotoxic Damage of the Basal Ganglia. Serotonin may modulate the effects of glutamate excitatory neurotransmission in the basal ganglia, as well as mediate glutamate receptor induced excitotoxicity. Experiments will determine how serotonin contributes to the regulation of basal ganglia gene expression following abnormal glutamate receptor stimulation. Completion of these studies will increase our understanding of how serotonin transmission influences gene expression patterns in the normal developing and adult basal ganglia; as well as in response to changes in dopamine and glutamate neurotransmission. Such information will increase our awareness of serotonin as a major afferent regulator of basal ganglia function and lead to the development of serotonin-based therapies to treat basal ganglia disease.