SEPTOHIPPOCAMPAL CHOLINERGIC AND NEUROTROPHIN MARKERS IN AGE-INDUCED COGNITIVE DECLINE

Messenger RNA (mRNA) molecules encoding proteins related to the presyn aptic cholinergic and neurotrophin systems were quantitated in the hip pocampus and basal forebrain of Long-Evans rats with spatial learning ability assessed in the Morris water maze. The reverse transcriptase-p olymerase chain reaction showed that the mRNAs for the low-affinity ne urotrophin receptor (p75-NTR) and the growth-associated protein GAP-43 were decreased in level in the basal forebrain of aged-impaired rats. Tn the hippocampus of these aged-impaired rats, the mRNA for VGF, ano ther neurotrophin-inducible gene, also was decreased. In situ hybridiz ation histochemistry revealed that mRNAs for nerve growth factor (NGF) and brain-derived neurotrophic factor increased in level in the aged rat hippocampus; when age effects were removed, NGF mRNA level remaine d significantly correlated with maze performance. Enzyme-linked immuno sorbent assay indicated that NGF protein was expressed at normal level s in the aged rat hippocampus. These mRNA and protein alterations may signify that a defect in neurotrophin signaling exists in the brains o f aged Long-Evans rats; underlying reduced plasticity responses in the basal forebrain cholinergic system. (C) 1998 Elsevier Science Inc.