Effect of cytokine treatment on the neurogenesis process in the brain of soman-poisoned mice

We previously described that enhanced proliferation of neural progenitors occurred in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ) of the mouse brain following soman poisoning. Then, a discrete number of these cells seemed to migrate and engraft into the main damaged brain regions (hippocampus; septum and amygdala) and subsequently differentiate into neurons. In the present study, the effect of a cytokine treatment on the neurogenesis process was evaluated. For this purpose, subcutaneous injection of a cocktail of 40 mu a/kg epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) was administered daily to soman-poisoned mice (110 mu g/kg soman and 5.0 mg/kg methyl nitrate atropine), from post-soman days 1 to 8. To label replicating neural progenitors, 200 mg/kg bromodeoxyuridine, (BrdU) was injected twice a day between post-soman days 6 and 8. Mice were sacrificed on post-soman day 9 or 34. On post-soman day 9, the cytokine treatment had no effect on the proliferation of neural progenitors in the SVZ and SGZ, as assessed by BrdU immunochemistry. However, this treatment seemed to promote the migration of neural precursor cells from the proliferative areas towards damaged brain regions. Indeed, in the CA1 hippocampal layer of soman-poisoned mice, on post-soman day 34, the cytokine treatment increased the number of healthy pyramidal neurons stained by hemalun-eosin dye. The cytokine treatment also augmented the number of BrdU-Iabeled cells in the CA1 hippocampal layer and amygdala. Interestingly. the administration of cytokines resulted in the differentiation of BrdU-positive cells into new neurons in the CA1 hippocampal layer, whereas astrocytic differentiation was preferentially observed in the amygdala. (c) 2005 Elsevier Ireland Ltd. All rights reserved.