Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice.
EMBO Molecular Medicine. 2014-08-06; 6(10): 1246-1262
DOI: 10.15252/emmm.201404228
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1. 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.
Pascual-Lucas M(1), Viana da Silva S(2), Di Scala M(3), Garcia-Barroso C(1),
González-Aseguinolaza G(3), Mulle C(2), Alberini CM(4), Cuadrado-Tejedor M(5),
Garcia-Osta A(6).
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 .
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.
© 2014 The Authors. Published under the terms of the CC BY 4.0 license.
DOI: 10.15252/emmm.201404228
PMCID: PMC4287930
PMID: 25100745 [Indexed for MEDLINE]