Characterization of chronic nicotine exposure on the survival of the spastic Han-Wistar rat.

Excitotoxicity has been implicated as a mechanism of cell death in many neurodegenerative disorders. Cell culture studies have shown that neuroprotection can be induced by preincubation with the acetylcholine agonist nicotine. We investigated the possible neuroprotective effects of nicotine in the spastic Han-Wistar rat, which suffers from glutamate excitotoxicity affecting two central nervous system regions: The hippocampus and the cerebellum. To investigate nicotine's possible neuroprotection, we treated 25-day-old mutant and normal siblings with 50-75 mg/l nicotine in their drinking solutions. The 75-ml/l dose significantly improved motor activity and increased longevity of the mutants (p<.05). To assess whether nicotine protected individual neurons, we performed hematoxylin and eosin (H&E) staining of brain sections. The histological data indicated that nicotine increased the survival of Purkinje cells in the mutants by as much as 50% but did not prevent cell death. To investigate whether the neuroprotection by nicotine was due to changes in nicotinic receptor expression, we performed immunohistochemical studies by staining for the alpha 3, alpha 4, and alpha 7 receptor subunits in mutant and normal rats. The alpha 4 subunit was upregulated by nicotine treatment in the cerebellum and was noted to have lower levels throughout the hippocampus of mutant animals. The alpha 3 and alpha 7 subunits showed no change in expression among all groups.