Insulin Growth Factor-I Promotes Functional Recovery After a Focal Lesion in the Dentate Gyrus

Author(s): Adhemar Liquitaya-Montiel, Andrea Aguilar-Arredondo, Clorinda Arias, Angelica Zepeda.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 11 , Issue 7 , 2012

Abstract:

The adult brain is plastic and able to reorganize structurally and functionally after damage. Growth factors are key molecules underlying the recovery process and among trophic molecules, Insulin-Like Growth Factor-I (IGF-I) is of particular interest given that it modulates neuronal and glial responses in the hippocampus including neurogenesis, which has been proposed as a mechanism of neurorepair. In this study we analyzed the effect of intracerebroventricular chronic infusion of IGF-I on functional recovery and morphological restoration after the induction of an excitotoxic lesion in the dentate gyrus (DG) of young-adult rats. Our results show that the lesion impairs contextual fear memory which is a DG dependent task, but not cued fear memory or performance in the open field motor task, which are independent of the DG integrity. Chronic administration of IGF-I, but not vehicle, promotes functional recovery to control levels in injured subjects. Analysis in NeuN immunoprocessed tissue revealed that the lesion volume was not different between groups and that the DG was not evidently restructured in the IGF-I treated group. Glial fibrillary acidic protein (GFAP) analysis revealed an increased astrocytic response in the injured region in both groups and Doublecortin (DCX) analysis showed a similar increase in number of newly born neurons in both groups. However, a remarkable increase in young neurons dendritic arborization was observed in the IGF-I treated group. These results provide evidence for IGF-I as a molecule mediating functional and cellular plasticity during a reorganization process after damage to a neurogenic niche.

Keywords: Plasticity, neurogenesis, hippocampus, brain damage, growth factors, IGF-1, Insulin-Like Growth Factor-I, neuronal, glial, morphological restoration

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Article Details

VOLUME: 11
ISSUE: 7
Year: 2012
Page: [818 - 828]
Pages: 11
DOI: 10.2174/1871527311201070818
Price: $58

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