Sarin Causes Early Differential Alteration and Persistent Overexpression in mRNAs Coding for Glial Fibrillary Acidic Protein (GFAP) and Vimentin Genes in the Central Nervous System of Rats

作者: Tirupapuliyar V. Damodaran , Magdalena A. Bilska , Ali A. Rahman , Mohamed B. Abou-Donia

DOI: 10.1023/A:1015508132137

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摘要: Neurotoxic effects of single dose 0.5 × LD50 sarin (O-isopropylmethylphosphonoflouridate) on central nervous system (CNS) male Sprague-Dawley rats were studied. We investigated the mRNA expression astroglial marker genes glial fibrillary acidic protein (GFAP) and vimentin to evaluate fate neuronal cells, because reactive gliosis is very often used assess extent CNS damage. Rats treated with 50 μg/kg/ml terminated at time-points 1 2 hours 1, 3, 7 days post-treatment. Control normal saline. Total RNA was extracted Northern blots hybridized cDNA probes for GFAP vimentin, as well 28S (control). The data obtained indicate that a (0.5 LD50) showed induction in transcript levels cortex, cerebellum, brainstem midbrain, spinal cord. distinct spatial-temporal differences each tissue Both induced hour all tissues studied except brainstem, where moderate high noted 3 days. Overexpressed remained more responsive such midbrain. Other tissues, cord, cerebellum downward trend either or both, It noteworthy both cortex (318 ± 12%) cord (368 relatively higher GFAP, whereas alone highest level overexpressed (284 11%). Overall it also clear are needed effective recovery involving co-ordinated alternating up- down-regulation these two key astrocyte genes, depending specificity. changes seen may be result dysfunction loss, accompanied by compensatory proliferation dedifferentiation astroglia. These could affect cell types, thus altering neuron-glia homeostasis.

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