Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound.
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.
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Silvia
S
Bolognin
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Mario
M
Buffelli
Department of Behavioral Studies, Charles River Finland, Kuopio, Finland.
Jukka
J
Puoliväli
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Electronic address: khalid.iqbal.ibr@gmail.com.
Khalid
K
Iqbal
D000284:Administration, Oral; D000375:Aging / Q000473:pathology / Q000502:physiology / Q000523:psychology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control / Q000523:psychology; D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage* / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007294:Inositol / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008568:Memory / Q000187:drug effects; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D011916:Rats, Inbred F344; D012307:Risk Factors
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; C000595095:peptide 021; D007294:Inositol
Alzheimer's disease; Cognitive aging; Neurogenesis; Neurotrophic factor; Peptidergic compound; Synaptic plasticity