Age-dependent alterations in nerve growth factor (NGF)-related proteins, sortilin, and learning and memory in rats.
The objective of this study was to evaluate the effects of aging on the performance of specific memory-related tasks in rats as well as to determine the levels of several nerve growth factor (NGF)-related proteins in relevant brain regions. The results indicated age-related impairments in spatial learning in a water maze task as well as deficits in recognition memory in a Spontaneous Novel Object Recognition task. In the prefrontal cortex and hippocampus, aged rats (compared to young controls) had elevated levels of the proneurotrophin, proNGF (+1.8-1.9 fold), p75(NTR) receptors (+1.6-1.8 fold) and sortilin (+1.8-2.1 fold), and decreased levels of mature NGF (-36 to 44%), and phospho-TrkA receptors (-45 to 49%). The results of this study support the argument that NGF signaling is altered in the aging brain, and that such alterations may contribute to an age-related decline in cognitive function. These results may also help to identify specific components of the NGF-signaling pathway that could serve as targets for novel drug discovery and development for age-related disorders of cognition (e.g., Alzheimer's disease).
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912, United States. aterry@mail.mcg.edu
Alvin V
AV
Terry
Ammar
A
Kutiyanawalla
Anilkumar
A
Pillai
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D047468:Immunoprecipitation; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D013550:Swimming; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D020932:Nerve Growth Factor; D009414:Nerve Growth Factors; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; D000099183:Sortilin; C514218:pro-nerve growth factor, rat