Zoli M, Pich E M, Cimino M, Lombardelli G, Peruzzi G, Fuxe K, Agnati L F, Cattabeni F
Institute of Human Physiology, University of Modena, Italy.
Brain Res Dev Brain Res. 1990 Jan 1;51(1):45-61. doi: 10.1016/0165-3806(90)90257-y.
Methylazoxymethanol acetate (MAM Ac) injected into pregnant rats at a dose of 25 mg/kg at gestational day 15 causes microcephaly due to an atrophy of various telencephalic areas, mainly neocortex, hippocampus and basal ganglia. Previous studies demonstrated alterations in various neurochemical markers of classical transmitter systems in these regions. The present paper deals with changes in peptide and tyrosine hydroxylase (TH)-containing neurons in MAM Ac-induced microcephaly using immunocytochemistry coupled with computer-assisted morphometry and microdensitometry. No change in the number of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in the neocortex and neuropeptide Y (NPY)-immunoreactive neurons in the nucleus caudatus-putamen was found whereas cholecystokinin (CCK)-and NPY-immunoreactive neurons in the neocortex and CCK- and VIP-immunoreactive neurons in the hippocampus were decreased. The reduction of the latter peptide containing neuronal populations led to a maintained density of cells in MAM Ac-exposed rats, due to the parallel reduction of the overall mass of these regions. TH immunoreactivity was found to be unchanged in the basal ganglia, and increased in the cerebral cortex in agreement with previous reports on noradrenaline cortical system after MAM Ac exposure. The present results show a heterogenous vulnerability of different peptide immunoreactive neuronal populations to MAM Ac exposure. The sparing of VIP- and NPY-immunoreactive neurons may be due to their late development in the neocortex and striatum, respectively. The hypothesis is introduced that cortical VIP interneurons can develop independent of marked alterations in the intrinsic circuitry of the cortical region.
在妊娠第15天给怀孕大鼠注射剂量为25mg/kg的乙酸甲基偶氮甲醇（MAM Ac），会因各种端脑区域萎缩，主要是新皮层、海马体和基底神经节萎缩，导致小头畸形。先前的研究表明这些区域中经典递质系统的各种神经化学标志物发生了改变。本文利用免疫细胞化学结合计算机辅助形态测量和显微密度测定法，研究了MAM Ac诱导的小头畸形中肽和含酪氨酸羟化酶（TH）神经元的变化。结果发现，新皮层中血管活性肠肽（VIP）免疫反应性神经元的数量以及尾状核-壳核中神经肽Y（NPY）免疫反应性神经元的数量没有变化，而新皮层中胆囊收缩素（CCK）和NPY免疫反应性神经元以及海马体中CCK和VIP免疫反应性神经元减少。由于这些区域总体质量的平行减少，后一种含肽神经元群体的减少导致MAM Ac暴露大鼠中细胞密度保持不变。在基底神经节中，TH免疫反应性未发现变化，而在大脑皮层中增加，这与先前关于MAM Ac暴露后去甲肾上腺素皮质系统的报道一致。目前的结果表明，不同肽免疫反应性神经元群体对MAM Ac暴露存在异质性易损性。VIP和NPY免疫反应性神经元的保留可能分别是由于它们在新皮层和纹状体中的发育较晚。本文提出了一个假说，即皮质VIP中间神经元可以独立于皮质区域内在回路的明显改变而发育。
