Molecular Responses of Corticostriatal Pyramidal Cells to Antipsychotic Drugs

皮质纹状体锥体细胞对抗精神病药物的分子反应

• 批准号: 8150117
• 负责人: NATHANIEL HEINTZ
• 金额: $ 26万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8150117
• 关键词: Affect; Antipsychotic Agents; Basal Ganglia; Biochemical; Cells; Cerebral cortex; Cognitive deficits; Collaborations; Corpus striatum structure; Data; Drug effect disorder; Ganglia; Genetic; Immunohistochemistry; In Situ Hybridization; Mediating; Mental disorders; Messenger RNA; Molecular; Molecular Profiling; Mus; Myxoid cyst; Neurons; Patients; Population; Primates; Public Health; Pyramidal Cells; Rodent; Schizophrenia; Symptoms; Testing; Therapeutic Effect; Transgenic Organisms; adapter protein; atypical antipsychotic; cell type; frontal lobe; inter-alpha-inhibitor; member; novel; novel therapeutics; programs; response; transcription factor

Hypofunction of cortico-basal ganglia circuits has been hypothesized to underlie some of the debilitating cognitive deficits and negative symptoms that are seen in schizophrenic patients. Antipsychotics are thought to mediate some of their therapeutic effects by normalizing this activity. However, the precise cell populations and the molecular changes involved in this response are still not fully understood. In Project 2 of this Conte center application, we hypothesize that cell-type specific changes in neurons projecting from the frontal cortex to the basal ganglia occur in response to typical and atypical antipsychotic drugs. To test this hypothesis, we will make use of a novel mRNA translational profiling approach. In Aim 1 of this project, we will perform these studies on two distinct cortico-striatal cell populations we have targeted genetically. In Aim 2, we will characterize two newly generated mouse lines that may give us translational profiling access to two additional cortico-striatal cell populations. Finally, in Aim 3, in collaboration with the other projects of this center, we will perform a functional analysis of molecules identified in our translational profiling studies of Aims 1 and 2.

皮质-基底神经节回路功能减退已被假设为精神分裂症患者中出现的一些衰弱性认知缺陷和阴性症状的基础。抗精神病药物被认为是通过使这种活动正常化来调节它们的一些治疗效果。然而，参与这种反应的精确细胞群和分子变化仍未完全了解。在Conte center应用的项目2中，我们假设从额叶皮层到基底神经节的神经元的细胞类型特异性变化发生在典型和非典型抗精神病药物的反应中。为了验证这一假设，我们将使用一种新的mRNA翻译分析方法。在这个项目的目标1中，我们将在两个不同的皮质纹状体细胞群上进行这些研究。在Aim 2中，我们将描述两个新生成的小鼠系，这可能使我们能够获得两个额外的皮质纹状体细胞群的翻译分析。最后，在Aims 3中，我们将与本中心的其他项目合作，对Aims 1和Aims 2中翻译分析研究中发现的分子进行功能分析。