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，以及对压力和抗抑郁药物作用的神经生物学反应中发挥作用。19例重度抑郁障碍（MDD）患者海马神经元和神经胶质细胞密度显著增加，神经元胞体大小显著减小。重度抑郁症的密度变化与自杀或性别无关。据推测，由于神经生长和突触连接标志物的减少，海马神经pil减少，导致神经元和胶质细胞密度增加，这是MDD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，重度抑郁症患者海马神经pil减少的假设。目的4-5检验了MDD患者海马神经生长和突触连接标志物减少的假设。在Aim 1中，MDD的体视学实验将估计整个海马的神经元和gila的总细胞数量和密度以及相应的体积。在Aim 2中，将使用高尔基银法测量MDD海马CA1和CA3亚区锥体神经元的脊柱密度、树突分支点数以及顶端和基部树突树的总长度。在Aim 3中，我们将测量MDD海马中胶质原纤维酸性蛋白（GFAP）免疫反应细胞体的密度和大小，以及GFAP免疫反应在星形胶质细胞中所占的面积比例。在Aim 4中，实验旨在从立体学角度估计MDD患者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）和多囊化神经细胞粘附分子（PSA-NCAM））的总免疫反应细胞数量和堆积密度。在Aim 5中，我们将进行实验，定量MDD患者吻侧海马CA3和CA4中BDNF和GAP-43 mRNA的表达。我们预测，Aim 4中BDNF和GAP-43蛋白表达的减少可能是继发于海马中相关基因表达的减少。在死后发现的MDD细胞变化可能是一些活着的MDD患者发现的海马萎缩的基础。

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.