IRS-2 deficiency impairs NMDA receptor-dependent long-term potentiation
| Autor: | José Luis Trejo, Sebastian Pons, Morris F. White, Juan Antonio Martin-Aldana, Ana María Sánchez-Pérez, Eduardo D. Martín, Deborah J. Burks, Carlos Acosta Umanzor, Lorena Menes, Marife Cano Jaimez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Cognitive Neuroscience medicine.medical_treatment Blotting Western education Hippocampus ComputingMilieux_LEGALASPECTSOFCOMPUTING Neurotransmission Biology Receptors N-Methyl-D-Aspartate Synaptic Transmission Mice Cellular and Molecular Neuroscience Internal medicine medicine Animals Immunoprecipitation long-term potentiation Mice Knockout synaptic plasticity diabetes Insulin Diabetes Long-term potentiation Articles NMDA receptor IRS2 insulin receptor signaling Synaptic fatigue Endocrinology nervous system Synaptic plasticity Insulin Receptor Substrate Proteins Female Neuroscience |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname CEREBRAL CORTEX r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) Repositori Universitat Jaume I Universitat Jaume I r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Cerebral Cortex (New York, NY) |
| ISSN: | 1047-3211 |
| Popis: | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.-- et al. The beneficial effects of insulin and insulin-like growth factor I on cognition have been documented in humans and animal models. Conversely, obesity, hyperinsulinemia, and diabetes increase the risk for neurodegenerative disorders including Alzheimer's disease (AD). However, the mechanisms by which insulin regulates synaptic plasticity are not well understood. Here, we report that complete disruption of insulin receptor substrate 2 (Irs2) in mice impairs long-term potentiation (LTP) of synaptic transmission in the hippocampus. Basal synaptic transmission and paired-pulse facilitation were similar between the 2 groups of mice. Induction of LTP by high-frequency conditioning tetanus did not activate postsynaptic N-methyl-D-aspartate (NMDA) receptors in hippocampus slices from Irs2 -/- mice, although the expression of NR2A, NR2B, and PSD95 was equivalent to wild-type controls. Activation of Fyn, AKT, and MAPK in response to tetanus stimulation was defective in Irs2 -/- mice. Interestingly, IRS2 was phosphorylated during induction of LTP in control mice, revealing a potential new component of the signaling machinery which modulates synaptic plasticity. Given that IRS2 expression is diminished in Type 2 diabetics as well as in AD patients, these data may reveal an explanation for the prevalence of cognitive decline in humans with metabolic disorders by providing a mechanistic link between insulin resistance and impaired synaptic transmission. © 2011 The Authors. This research was funded, in part, by the following grants: SAF2008-00011 (to D.J.B.), BFU2007-60195 (to J.L.T.), BFU2008-04196 (to E.D.M.), Ministerio de Ciencia e Innovación; CIBER de la Diabetes y Enfermedades Metabólicas (to D.J.B.), Instituto de Salud Carlos III; PAI07-0042-1097 and PEII10-0095-872 (to E.D.M.) from Consejería de Educación Ciencia y Cultura of the Junta Cultural de Castilla-La Mancha (JCCM), PI-2007/49 (to E.D.M.) from Fundación para la investigación sanitaria de Castilla-La Mancha; EMER-07/012 (to D.J.B.), Instituto de Salud Carlos III; Regenerative Medicine Program of Valencia (to D.J.B.); and the INCRECyT project (to E.D.M.) from European Social Fund and JCCM. |
| Databáze: | OpenAIRE |
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