Effect of vinconate against regional age-related changes in the gerbil brain

Abstract

We investigated age-related changes in the binding sites of muscarinic acetylcholine, forskolin, adenosine 3', 5' -cyclic monophosphatee (cAMP), and of a voltage-dependent L-type calcium channel blocker in the gerbil brain receptor autoradiography. [ 3H]Quinuclidinyl benzilate (QNB), [ 3H]forskolin, [ 3H]cAMP, and [ 3H]PN200-110 were used to label muscarinic receptors, adenylate cyclase, cAMP-dependent protein kinase, and L-type calcium channels, respectively. In middle-aged animals (16-month-old gerbils), [ 3H]QNB, [ 3H]PN200-110, [ 3H]forskolin, and [ 3H]cAMP binding sites were elevated in the hippocampal region compared with that of young gerbils (4 weeks old). Further, a significant elevation in [ 3H]forskolin binding was seen in the nucleus accumbens. In contrast, [ 3H]QNB, [ 3H]PN200-110, and [ 3H]forskolin binding sites were reduced in the cerebellum, neocortex and thalamus, and hypothalamus in middle-aged animals, respectively, [ 3H]cAMP binding was not altered in other regions except for an elevation in the hippocampus. Thus, the age-related alterations in receptor binding may proceed by different mechanisms in various brain regions. Chromic vinconate treatment partly modulated the age-related alterations in [ 3H]QNB, [ 3H]forskolin, and [ 3H]cAMP binding in the hippocampus, but not that of [ 3H]PN200-110. Vinconate also regulated the age-related changes in [ 3H]forskolin binding in the nucleus accumbens. These results indicate that the age-related alterations in the binding sites of muscarinic acetylcholine, forskolin, cAMP, and L-type calcium channel blocker occur in particular in the hippocampus. Further, they suggest that a novel vince alkaloid derivative, vinconate, can partly modulate age-related changes in the binding sites.