Cholinergic denervation-induced increase of chelatable zinc in mossy-fiber region of the hippocampal formation.

Chelatable zinc has repeatedly been associated with hippocampal mossy fibers, but the neurobiological functions of the zinc have remained unclear. Zinc is a constituent of the 7S Nerve Growth Factor (NGF) molecule. The hippocampal area is rich in neurotrophic factors and cholinergic deafferentation of the hippocampus appears to activate these neurotrophic factors. In this paper we report that cholinergic deafferentation of the hippocampus causes a transient rise in mossy-fiber zinc, as measured by zinc-dithizonate histochemistry. The changes are not significant until 10 days after the septal lesion, and the zinc returns to control levels by 21-28 days. Dithizonate has an association constant of 10(-15) with zinc, while NGF has an association constant of 10(-11). Thus densitometric measurement of zinc dithizone within the hippocampus may be a quantitative histochemical marker of a zinc-associated nerve growth-like substance. The data support recent findings that nerve growth-like factors increase in the hippocampal area following deafferentation, and in addition suggest that zinc is a critical factor in the regulation of trophic phenomena in the hippocampal formation.