Septo-hippocampal cholinergic and neurotrophin markers in age-induced cognitive decline.
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.
Sugaya
K
K
Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA.
Greene
R
R
Personett
D
D
Robbins
M
M
Kent
C
C
Bryan
D
D
Skiba
E
E
Gallagher
M
M
McKinney
M
M
D000375:Aging / Q000502:physiology* / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D018782:Maze Learning; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D019922:GAP-43 Protein; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase