92 research outputs found

    IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation

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    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

    Genetic variation between Phytophthora cactorum isolates differing in their ability to cause crown rot in strawberry

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    Analysis of 44 isolates of Phytophthora cactorum, isolated from strawberry and other hosts, by AFLP showed that the crown rot pathotype is different from leather rot isolates and from P. cactorum isolated from other hosts. 16 of 23 crown rot isolates, including isolates from Europe, Japan, Australia, and New Zealand, were identical in an analysis based on 96 polymorphic bands from seven primer combinations. Leather rot isolates of strawberry could not be distinguished from isolates from other hosts. The pathogenicity test of all 44 isolates on strawberry plants mostly gave unambiguous results, except for three American isolates, which seemed to have reduced aggressiveness compared to the crown rot isolates. These isolates also differed in the AFLP analysis. Comparing information on the origin of the isolates with results from the pathogenicity test, showed that isolates from strawberry fruits or petioles could be either leather rot or crown rot pathotypes. None of the isolates from hosts other than strawberry caused crown rot symptoms in strawberr
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