Sugaya K, Greene R, Personett D, Robbins M, Kent C, Bryan
D, Skiba E, Gallagher M,
McKinney M
Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA.
Messenger RNA (mRNA) molecules encoding proteins related to the presynaptic
cholinergic and
neurotrophin systems were quantitated in the hippocampus and basal
forebrain of Long-Evans rats
with spatial learning ability assessed in the Morris water maze. The
reverse transcriptase-polymerase
chain reaction showed that the mRNAs for the low-affinity neurotrophin
receptor (p75-NTR) and
the growth-associated protein GAP-43 were decreased in level in the
basal forebrain of
aged-impaired rats. In the hippocampus of these aged-impaired rats,
the mRNA for VGF, another
neurotrophin-inducible gene, also was decreased. In situ hybridization
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
remained significantly correlated with maze performance. Enzyme-linked
immunosorbent assay indicated that NGF protein
was expressed at normal levels in the aged rat hippocampus. These mRNA
and protein alterations
may signify that a defect in neurotrophin signaling exists in the brains
of aged Long-Evans rats,
underlying reduced plasticity responses in the basal forebrain cholinergic
system.