Progression of age-associated cognitive impairment correlates with quantitative and qualitative loss of TrkA receptor protein in nucleus basalis and cortex.
A direct correlation between disease progression and reduced expression of TrkA receptor in cholinergic neurons has been documented in neurocognitive pathologies including Alzheimer's disease. We investigated whether reduced expression of TrkA protein might also correlate with the level of cognitive impairment in age-associated cognitive impairment. Quantitative and qualitative measurements of TrkA protein levels in the cortex and nucleus basalis of aged rats that had been well-characterized behaviorally as 'unimpaired', 'mildly impaired' or 'fully impaired' demonstrated significant changes in TrkA expression. In the mildly impaired cognitive state phenotypic silencing of TrkA was detected in neurons expressing TrkA at high density but before cholinergic atrophy or loss of TrkA+ neurons was detected. In the fully impaired cognitive state a significant loss in TrkA+ cholinergic neurons together with a more significant phenotypic silencing of TrkA expression then took place. These data suggest that TrkA+ cholinergic cells are associated with cognition, TrkA could be a biomarker of the cognitive state and phenotypic loss of TrkA precedes neuronal loss and probably sensitizes cells to death. We speculate that neurotrophic deficits may be a shared mechanism for cognitive decline in aging and Alzheimer's disease.
Saragovi
H Uri
HU
Department of Pharmacology and Therapeutics, Oncology/Cancer Center, McGill University, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada. Uri.Saragovi@mcgill.ca
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism*; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism*; D003952:Diagnostic Imaging; D018450:Disease Progression; D018782:Maze Learning / Q000502:physiology; D010641:Phenotype; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*
D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA