Neuronal and Glial Changes in Rat Hippocampal Formation after Cholinergic Deafferentation

The effects of cholinergic insult were studied in the hippocampal formation of cholinergic lesioned rats at metabolic and cellular levels by in vivo nuclear magnetic resonance spectrometry and immuno-histochemical approaches. Cholinergic deafferentation was induced by injection of the cholinergic immunotoxin 192 IgG-saporin into the medial septum. The immunotoxin effects were tested at 3, 7, and 30 days post-lesion. Rats with cholinergic deafferentation of the hippocampus showed a lack of NeuN immunoreactivity cells, indicating neuronal loss in hippocampal formation. This neuronal loss was more pronounced in the dentate gyrus, underlining the greater sensitivity of this region to the cholinergic insult. Interestingly, this neuronal loss was not associated with metabolic alteration. These data suggest that the remaining neurons upregulated their functional activity, which would contribute to maintaining the relatively stable level of metabolites and memory abilities. No alteration in GFAP and OX42 immunostaining and in glutamine and myoionositol metabolite concentration was observed in the deafferented