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.
Neurobiol Aging. 1998 Jul-Aug;19(4):351-61. doi: 10.1016/s0197-4580(98)00072-4.
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.
