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EMBO Mol Med. 2014 Oct;6(10):1246-62. doi: 10.15252/emmm.201404228.

Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice.

Author information

1
Neurosciences Division, Center for Applied Medical Research, CIMA University of Navarra, Pamplona, Spain.
2
Interdisciplinary Institute for Neuroscience, Université of Bordeaux CNRS UMR 5297, Bordeaux, France.
3
Gene Therapy and Hepatology Division, Center for Applied Medical Research CIMA University of Navarra, Pamplona, Spain.
4
Center for Neural Science, New York University, New York, NY, USA.
5
Neurosciences Division, Center for Applied Medical Research, CIMA University of Navarra, Pamplona, Spain Department of Anatomy, School of Medicine University of Navarra, Pamplona, Spain.
6
Neurosciences Division, Center for Applied Medical Research, CIMA University of Navarra, Pamplona, Spain agosta@unav.es.

Abstract

Insulin-like growth factor 2 (IGF2) was recently found to play a critical role in memory consolidation in rats and mice, and hippocampal or systemic administration of recombinant IGF2 enhances memory. Here, using a gene therapy-based approach with adeno-associated virus (AAV), we show that IGF2 overexpression in the hippocampus of aged wild-type mice enhances memory and promotes dendritic spine formation. Furthermore, we report that IGF2 expression decreases in the hippocampus of patients with Alzheimer's disease, and this leads us to hypothesize that increased IGF2 levels may be beneficial for treating the disease. Thus, we used the AAV system to deliver IGF2 or IGF1 into the hippocampus of the APP mouse model Tg2576 and demonstrate that IGF2 and insulin-like growth factor 1 (IGF1) rescue behavioural deficits, promote dendritic spine formation and restore normal hippocampal excitatory synaptic transmission. The brains of Tg2576 mice that overexpress IGF2 but not IGF1 also show a significant reduction in amyloid levels. This reduction probably occurs through an interaction with the IGF2 receptor (IGF2R). Hence, IGF2 and, to a lesser extent, IGF1 may be effective treatments for Alzheimer's disease.

KEYWORDS:

Alzheimer's disease; IGF1; IGF2; IGF2R; synaptic plasticity

PMID:
25100745
PMCID:
PMC4287930
DOI:
10.15252/emmm.201404228
[Indexed for MEDLINE]
Free PMC Article

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