Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study.
Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study.
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DOI：
10.1002/aur.62
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发表时间：
2009-02
期刊：
影响因子：
4.7
通讯作者：
Blatt, Gene J.
中科院分区：
文献类型：
--
作者：
Yip, Jane;Soghomonian, Jean Jacques;Blatt, Gene J.
侧位的齿状核在小脑中处于接收来自小脑外侧半球浦肯野细胞输入的关键位置，参与运动和认知功能。尽管在儿童和成人自闭症患者中使用尼氏染色对四个小脑核的神经病理学进行了定性报道，但令人惊讶的是，尽管有报道称小脑后外侧半球的浦肯野细胞减少，但齿状核受到的影响较小。为了确定至关重要的gaba能系统中是否存在潜在的异常，我们通过原位杂交组织化学方法测量了齿状体中限速gaba合成酶谷氨酸脱羧酶（GAD） 65型。GAD65 mRNA标记揭示了成人对照和自闭症死后大脑中两个不同的神经元亚群：小细胞（直径约10-12µm，推测为中间神经元）和大细胞（直径约18-20µm，可能反馈给IO神经元）。与对照组相比，自闭症组中较大的标记细胞中GAD65 mRNA水平平均降低51% （p=0.009；独立t检验），但较小的细胞亚群中没有。这表明自闭症组小脑固有回路的紊乱可能干扰下橄榄神经元的同步放电，以及浦肯野细胞放电和齿状核输入的时间。这些关键回路中关键神经基质的紊乱可能会破坏自闭症大脑中运动和/或认知脑关联区域的传入信号，这可能会导致自闭症显著的行为后果特征。
The laterally positioned dentate nuclei lie in a key position in the cerebellum to receive input from Purkinje cells in the lateral cerebellar hemisphere participating in both motor and cognitive functions. Although neuropathology of the four cerebellar nuclei using Nissl staining has been qualitatively reported in children and adults with autism, surprisingly the dentate nuclei appeared less affected despite reported reductions in Purkinje cells in the posterolateral cerebellar hemisphere. To determine any underlying abnormalities in the critically important GABAergic system, the rate-limiting GABAsynthesizing enzyme, glutamic acid decarboxylase (GAD) type 65 was measured via in situ hybridization histochemistry in dentate somata. GAD65 mRNA labeling revealed two distinct subpopulations of neurons in adult control and autism post-mortem brains: small-sized cells (about 10–12 µm in diameter, presumed interneurons) and larger-sized neurons (about 18–20 µm in diameter, likely feedback to IO neurons). A mean 51% reduction in GAD65 mRNA levels was found in the larger labeled cells in the autistic group compared to the control group (p=0.009; independent t-test) but not in the smaller cell subpopulation. This suggests a disturbance in the intrinsic cerebellar circuitry in the autism group potentially interfering with the synchronous firing of inferior olivary neurons, and the timing of Purkinje cell firing and inputs to the dentate nuclei. Disturbances in critical neural substrates within these key circuits could disrupt afferents to motor and/or cognitive cerebral association areas in the autistic brain likely contributing to the marked behavioral consequences characteristic of autism.
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影响因子：
14.5
作者：
Bailey, A;Luthert, P;Lantos, P
通讯作者：
Lantos, P
影响因子：
2.5
作者：
BATINI, C;COMPOINT, C;GUEGAN, M
通讯作者：
GUEGAN, M
影响因子：
1.7
作者：
Garifoli, A;Scardilli, G;Perciavalle, V
通讯作者：
Perciavalle, V
影响因子：
2.5
作者：
BUISSERETDELMAS, C;ANGAUT, P
通讯作者：
ANGAUT, P
DOI：
10.1111/j.1749-6632.2002.tb07575.x
发表时间：
2002-01-01
期刊：
CREBELLUM: RECENT DEVELOPMENTS IN CEREBELLAR RESEARCH
影响因子：
--
作者：
Dum, RP;Li, C;Strick, PL
通讯作者：
Strick, PL