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Insulin Receptor β-Subunit Haploinsufficiency Impairs Hippocampal Late-Phase LTP and Recognition Memory

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Abstract

The insulin receptor (IR) is a protein tyrosine kinase playing a pivotal role in the regulation of peripheral glucose metabolism and energy homoeostasis. IRs are also abundantly distributed in the cerebral cortex and hippocampus, where they regulate synaptic activity required for learning and memory. As the major anabolic hormone in mammals, insulin stimulates protein synthesis partially through the activation of the PI3K/Akt/mTOR pathway, playing fundamental roles in neuronal development, synaptic plasticity and memory. Here, by means of a multidisciplinary approach, we report that long-term synaptic plasticity and recognition memory are impaired in IR β-subunit heterozygous mice. Since IR expression is diminished in type-2 diabetes as well as in Alzheimer’s disease (AD) patients, these data may provide a mechanistic link between insulin resistance, impaired synaptic transmission and cognitive decline in humans with metabolic disorders.

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Acknowledgments

This work was supported by grants from the Italian Ministry of Health to IRCCS Neurological Institute “C. Mondino” (Ricerca Corrente 2009–2011) to RN. MDA is financially supported by a grant from the Alzheimer’s Association (NIRG-11-204588). We thank Dr. Roberto Arriga for providing the mice. We are also indebted to Dr. Mauro Federici for excellent technical assistance.

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Correspondence to Robert Nisticò or Marcello D’Amelio.

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Robert Nisticò, Virve Cavallucci and Sonia Piccinin contributed equally to this work.

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Nisticò, R., Cavallucci, V., Piccinin, S. et al. Insulin Receptor β-Subunit Haploinsufficiency Impairs Hippocampal Late-Phase LTP and Recognition Memory. Neuromol Med 14, 262–269 (2012). https://doi.org/10.1007/s12017-012-8184-z

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  • DOI: https://doi.org/10.1007/s12017-012-8184-z

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