Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia
Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia
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DOI：
10.1001/archpsyc.57.1.65
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发表时间：
2000-01-01
影响因子：
--
通讯作者：
Lewis, DA
中科院分区：
文献类型：
--
作者：
Glantz, LA;Lewis, DA
背景：精神分裂症的病理生理特征似乎与背外侧前额皮质突触连通性的改变有关。考虑到第3层锥体神经元在皮质皮质和丘脑皮质连接中发挥的核心作用，我们假设精神分裂症患者对这些神经元的兴奋性输入发生了改变。方法：为了验证这一假设，我们测定了15名精神分裂症患者、15名正常对照患者和15名患有精神疾病的非精神分裂症患者（称为精神病患者）的高尔基浸染锥体神经元基底树突上的树突棘的密度，这是兴奋输入的标记。这些树突棘位于背外侧前额叶皮层第3层的浅层和深层（46区）以及初级视觉皮层第3层（17区）。结果：仅46区深3层锥体神经元对脊柱密度诊断有显著影响（P = 0.006）。与正常对照组（P = 0.004）和精神病组（P = 0.08）相比，精神分裂症组这些神经元上的脊柱密度分别下降了23%和16%。相比之下，46区浅层3神经元棘密度（P = 0.09）和17区棘密度（P = 0.08）在3个被试组间无显著差异。此外，抗精神病药物治疗的精神病患者与正常对照组之间，46区深3层神经元的脊柱密度无显著差异（P = 0.81）。结论：背外侧前额叶皮层第3层锥体细胞树突棘密度的区域特异性和疾病特异性下降与精神分裂症患者皮层和/或丘脑兴奋性输入神经元数量改变的假设相一致。
Background: The pathophysiological characteristics of schizophrenia appear to involve altered synaptic connectivity in the dorsolateral prefrontal cortex. Given the central role that layer 3 pyramidal neurons play in corticocortical and thalamocortical connectivity, we hypothesized that the excitatory inputs to these neurons are altered in subjects with schizophrenia.Methods: To test this hypothesis, we determined the density of dendritic spines, markers of excitatory inputs, on the basilar dendrites of Golgi-impregnated pyramidal neurons in the superficial and deep portions of layer 3 in the dorsolateral prefrontal cortex (area 46) and in layer 3 of the primary visual cortex (area 17) of 15 schizophrenic subjects, 15 normal control subjects, and 15 nonschizophrenic subjects with a psychiatric illness (referred to as psychiatric subjects).Results: There was a significant effect of diagnosis on spine density only for deep layer 3 pyramidal neurons in area 46 (P = .006). In the schizophrenic subjects, spine density on these neurons was decreased by 23% and 16% compared with the normal control (P = .004) and psychiatric (P = .08) subjects, respectively. In contrast, spine density on neurons in superficial layer 3 in area 46 (P = .09) or in area 17 (P = .08) did not significantly differ across the 3 subject groups. Furthermore, spine density on deep layer 3 neurons in area 46 did not significantly (P = .81) differ between psychiatric subjects treated with antipsychotic agents and normal controls.Conclusion: This region- and disease-specific decrease in dendritic spine density on dorsolateral prefrontal cortex layer 3 pyramidal cells is consistent with the hypothesis that the number of cortical and/or thalamic excitatory inputs to these neurons is altered in subjects with schizophrenia.