IRS-2 deficiency impairs NMDA receptor-dependent long-term potentiation
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Other documents of the author: Sánchez-Pérez, Ana María; Martín, Eduardo D.; Trejo, José Luis; Martín Aldana, Juan Antonio; Cano Jaimez, Marife; Pons, Sebastian; Acosta Umanzor, Carlos; Menes, Lorena; White, Morris F.; Burks, Deborah J.
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Title
IRS-2 deficiency impairs NMDA receptor-dependent long-term potentiationAuthor (s)
Date
2012-08Publisher
Oxford University PressISSN
1047-3211; 1460-2199Type
info:eu-repo/semantics/articlePublisher version
http://cercor.oxfordjournals.org/content/22/8/1717.full.pdf+htmlVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
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 neurodeg ... [+]
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 longterm
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-Daspartate
(NMDA) receptors in hippocampus slices from Irs22/2
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 Irs22/2 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 [-]
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Cerebral Cortex, 2012, agost, Vol. 22, num. 8Rights
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