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Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects

Citation

Trejo, JL and Piriz, J and Llorens-Martin, MV and Fernandez, AM and Bolos, M and LeRoith, D and Nunez, A and Torres-Aleman, I, Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects, Molecular Psychiatry, 12, (12) pp. 1118-1128. ISSN 1359-4184 (2007) [Refereed Article]

DOI: doi:10.1038/sj.mp.4002076

Abstract

Increasing evidence indicates that circulating insulin-like growth factor I (IGF-I) acts as a peripheral neuroactive signal participating not only in protection against injury but also in normal brain function. Epidemiological studies in humans as well as recent evidence in experimental animals suggest that blood-borne IGF-I may be involved in cognitive performance. In agreement with observations in humans, we found that mice with low-serum IGF-I levels due to liver-specific targeted disruption of the IGF-I gene presented cognitive deficits, as evidenced by impaired performance in a hippocampal-dependent spatial-recognition task. Mice with serum IGF-I deficiency also have disrupted long-term potentiation (LTP) in the hippocampus, but not in cortex. Impaired hippocampal LTP was associated with a reduction in the density of glutamatergic boutons that led to an imbalance in the glutamatergic/GABAergic synapse ratio in this brain area. Behavioral and synaptic deficits were ameliorated in serum IGF-I-deficient mice by prolonged systemic administration of IGF-I that normalized the density of glutamatergic boutons in the hippocampus. Altogether these results indicate that liver-derived circulating IGF-I affects crucial aspects of mature brain function; that is, learning and synaptic plasticity, through its trophic effects on central glutamatergic synapses. Declining levels of serum IGF-I during aging may therefore contribute to age-associated cognitive loss.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Bolos, M (Dr Marta Bolos Jurado)
ID Code:87501
Year Published:2007
Web of Science® Times Cited:113
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-11-20
Last Modified:2013-11-20
Downloads:0

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