精神分裂症患者前额叶皮质中抑制性中间神经元上谷氨酸能神经传递的疾病特异性改变。
Disease-specific alterations in glutamatergic neurotransmission on inhibitory interneurons in the prefrontal cortex in schizophrenia.
作者信息
Woo Tsung-Ung W, Kim Amy M, Viscidi Emma
机构信息
Laboratory for Structural and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478, USA.
出版信息
Brain Res. 2008 Jul 7;1218:267-77. doi: 10.1016/j.brainres.2008.03.092. Epub 2008 Apr 16.
Abstract
Glutamatergic modulation of inhibitory interneurons plays a crucial role in shaping the flow of information in the cerebral cortex. In a cohort of postmortem human brains from schizophrenia (n=20), bipolar disorder (n=20) and normal control (n=20) subjects, we colocalized the mRNA for the N-methyl-d-aspartate (NMDA) receptor NR2A subunit, labeled with [35S], and the mRNA for the gamma-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD)67, labeled with digoxigenin. We found that the density of GAD67+ neurons in layers 2-5 of the prefrontal cortex was decreased by 27-36% in both schizophrenia and bipolar disorder. In addition, the density of the GAD67+/NR2A+ neurons was decreased by 57% and 49% in layers 3 and 4, respectively, in schizophrenia, but it was unchanged in bipolar disorder. These findings raise the possibility that glutamatergic innervation of inhibitory interneurons via the NMDA receptor in the prefrontal cortex may be selectively altered in schizophrenia.
摘要
抑制性中间神经元的谷氨酸能调节在塑造大脑皮层信息流方面起着关键作用。在一组来自精神分裂症患者（n = 20）、双相情感障碍患者（n = 20）和正常对照者（n = 20）的死后人类大脑中，我们将用[35S]标记的N-甲基-D-天冬氨酸（NMDA）受体NR2A亚基的mRNA与用地高辛标记的γ-氨基丁酸（GABA）合成酶谷氨酸脱羧酶（GAD）67的mRNA进行共定位。我们发现，在精神分裂症和双相情感障碍患者中，前额叶皮层2 - 5层中GAD67 +神经元的密度降低了27% - 36%。此外，在精神分裂症患者中，3层和4层中GAD67 + / NR2A +神经元的密度分别降低了57%和49%，但在双相情感障碍患者中则没有变化。这些发现增加了一种可能性，即前额叶皮层中通过NMDA受体对抑制性中间神经元的谷氨酸能神经支配在精神分裂症中可能被选择性改变。
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