Journal
NEUROBIOLOGY OF AGING
Volume 35, Issue 9, Pages 2134-2146Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.02.017
Keywords
Cognitive aging; Alzheimer's disease; Neurogenesis; Synaptic plasticity; Neurotrophic factor; Peptidergic compound
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Funding
- Charles River Labs, Finland
- New York State Office of People with Developmental Disabilities
- Alzheimer's Drug Discovery Foundation, New York, NY, USA [20121203]
- University of Verona, Fondazione Cariverona project Verona Nanomedicine Initiative
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Aging is characterized by a progressive decline of cognitive performance, which has been partially attributed to structural and functional alterations of hippocampus. Importantly, aging is the major risk factor for the development of neurodegenerative diseases, especially Alzheimer's disease. An important therapeutic approach to counteract the age-associated memory dysfunctions is to maintain an appropriate microenvironment for successful neurogenesis and synaptic plasticity. In this study, we show that chronic oral administration of peptide 021 (P021), a small peptidergic neurotrophic compound derived from the ciliary neurotrophic factor, significantly reduced the age-dependent decline in learning and memory in 22 to 24-month-old Fisher rats. Treatment with P021 inhibited the deficit in neurogenesis in the aged rats and increased the expression of brain derived neurotrophic factor. Furthermore, P021 restored synaptic deficits both in the cortex and the hippocampus. In vivo magnetic resonance spectroscopy revealed age-dependent alterations in hippocampal content of several metabolites. Remarkably, P021 was effective in significantly reducing myoinositol (INS) concentration, which was increased in aged compared with young rats. These findings suggest that stimulating endogenous neuroprotective mechanisms is a potential therapeutic approach to cognitive aging, Alzheimer's disease, and associated neurodegenerative disorders and P021 is a promising compound for this purpose. (C) 2014 Elsevier Inc. All rights reserved.
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