Hippocampal atrophy in major depression

描述（由申请人提供）：海马体的可塑性在学习和记忆以及对应激和抗抑郁药物作用的神经生物学反应中起作用。19例重性抑郁症（MDD）患者海马神经元和胶质细胞密度明显增加，神经元索马体积明显减小。MDD密度的变化与自杀或性别无关。据推测，海马神经元减少，响应于神经生长和突触连接的标记物减少，导致神经元和神经胶质密度增加，是MDD中海马组织病理学的微观基础。目的1-3检验与正常对照相比，MDD中海马神经元减少的假设。目的4-5检验MDD中海马中神经生长和突触连接的标记物减少的假设。在目标1中，MDD的体视学实验将估计神经元和神经胶质细胞的总细胞数和密度以及整个海马的相应体积。目的2：采用Golgi银法测量MDD患者海马CA 1、CA 3区锥体神经元树突棘密度、树突分支点数、树突顶端和基底端树突总长度。在目标3中，将在MDD的海马中测量胶质细胞酸性蛋白（GFAP）免疫反应性细胞体的密度和大小，以及星形胶质细胞中GFAP免疫反应性占据的面积分数。在目的4中，设计实验以体视学地估计MDD中整个海马中突触可塑性标记物[脑源性神经营养因子（BDNF）、生长相关蛋白-43（GAP-43）和聚唾液酸化神经细胞粘附分子（PSA-NCAM）]的总免疫反应细胞数和堆积密度。在目的5中，将进行实验以定量MDD中头侧海马的CA 3和CA 4中BDNF和GAP-43的mRNA。据预测，Aim 4中BDNF和GAP-43蛋白表达的假设降低将继发于海马中基因表达的相关降低。在MDD死后检测到的细胞变化可能是一些MDD活体受试者检测到的海马萎缩的基础。

DESCRIPTION (provided by applicant): Plasticity in the hippocampus plays a role in learning and memory, and in neurobiological responses to stress and antidepressant drug action. A significant increase in neuron and glial cell density and a decrease in neuronal soma size has been detected in hippocampus of 19 subjects with major depressive disorder (MDD). The changes in density in MDD were independent of suicide or gender. It is hypothesized that a decrease in hippocampal neuropil, in response to diminished markers of neural growth and synaptic connection, resulting in an increase in neuronal and glial density, is the microscopic basis for the histopathology of the hippocampus in MDD. Aims 1-3 examine the hypothesis that in MDD there is a decrease in hippocampal neuropil, as compared to normal controls. Aims 4-5 examine the hypothesis that there will be diminished markers of neural growth and synaptic connection in the hippocampus in MDD. In Aim 1, stereological experiments in MDD will estimate the total cell number and density of neurons and gila and the corresponding volume throughout the entire hippocampus. In Aim 2, the Golgi silver method will be used to measure spine density, number of dendritic branch points and total length of apical and basal dendritic trees of pyramidal neurons in hippocampal CA1 & CA3 subfields in MDD. In Aim 3, the density and size of glial fibrillary acidic protein (GFAP) -immunoreactive cell bodies, and the areal fraction occupied by GFAP-immunoreactivity in astrocytes will be measured in the hippocampus in MDD. In Aim 4, experiments are designed to stereologically estimate the total immunoreactive cell number and packing density of markers of synaptic plasticity [brain derived neurotrophic factor (BDNF), growth associated protein-43 (GAP-43) and polysialylated-nerve cell adhesion molecule (PSA-NCAM)] throughout the hippocampus in MDD. In Aim 5, experiments will be carried out to quantify mRNA for BDNF and GAP-43 in CA3 and CA4 of the rostral hippocampus in MDD. It is predicted that the hypothesized decrease in expression of BDNF and GAP-43 protein in Aim 4 will be secondary to related decreases in gene expression in the hippocampus. Cellular changes detected in MDD postmortem may underlie hippocampal atrophy detected by some in living subjects with MDD.