Long-term effects of cytokine treatment on cognitive behavioral recovery and neuronal regeneration in soman-poisoned mice.

摘要

Increasing numbers of reports have substantiated to date, a beneficial influence of cytokine treatment on neurogenesis processes in damaged rodent brains. Most of these investigations further revealed that cytokine treatment induces either partial or full recovery of cognitive behavior impaired by cerebral lesions. Hence, we investigated the effects of a cytokine treatment on neuronal regeneration and cognitive behavior in mice subjected to nerve agent exposure. Subcutaneous injection of a mixture of 40 mug/kg fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) was administered daily over 8 days to soman-poisoned mice (1.2 LD50 soman). Memory performances (T-maze and Morris water maze) and emotional behavior (elevated plus maze; auditory and contextual response in a fear conditioning task) were assessed on post-soman days 30 and 90. Brains were collected on post-soman days 9, 30 and 90 so as to perform NeuN-immunohistochemistry in the hippocampus and amygdala (neuronal regeneration quantification). Following soman-induced brain lesions, a spontaneous neuronal regeneration occurred in both the hippocampus and amygdala. Cytokine treatment enhanced neuronal regeneration in the hippocampus however not in the amygdala. Soman poisoning fostered altogether memory impairments as well as anxiety or fear-like behavioral disturbances in mice. A spontaneous recovery of standard emotional behavior occurred overtime. Such a recovery displayed significantly enhanced speed under cytokine treatment. Unfortunately, no memory performance recovery was evidenced in soman-intoxicated mice whether treated or not with cytokines.