Age-dependent biphasic changes in ischemic sensitivity in the striatum of Huntington's disease R6/2 transgenic mice

Journal of Neurophysiology
Gloria J Klapstein, M S Levine

Abstract

We used the oxygen/glucose deprivation (OGD) model of ischemia in corticostriatal brain slices to test the hypothesis that metabolic deficiencies in R6/2 transgenic Huntington's disease (HD) mice will impair their recovery from an ischemic challenge. Corticostriatal extracellular field excitatory postsynaptic potentials (fEPSPs) were evoked in transgenic and wild-type (WT) mice in three age groups: 3-4 wk, before the overt behavioral phenotype develops; 5-9 wk, as overt behavioral symptoms begin; and 10-15 wk when symptoms were most severe. OGD for 8 min completely and reversibly inhibited fEPSPs. Although responses of 3-4 wk WTs showed a tolerance to ischemia and recovered rapidly, ischemic sensitivity developed progressively; at 5-9 and 10-15 wk, responses recovered more slowly from OGD. In contrast, although 3-4 wk R6/2 transgenic fEPSPs showed significantly more ischemic sensitivity than their WT counterparts, the R6/2 fEPSPs maintained a relative tolerance to ischemia at 5-9 and 10-15 wk. As a result, a "crossover" point occurred, roughly coinciding with the development of the overt behavioral phenotype (5-9 wk), after which time R6/2 fEPSPs were significantly more resistant to ischemia than WT responses. The increased isc...Continue Reading

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Citations

Jun 15, 2013·Cell Death and Differentiation·G KreinerR Parlato
Feb 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rona K GrahamMichael R Hayden
Oct 12, 2004·Trends in Neurosciences·Michael S LevineMarie-Françoise Chesselet
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Apr 27, 2012·Inflammopharmacology·G Joseph BroussardGloria J Klapstein
Jan 13, 2021·International Journal of Molecular Sciences·Johannes BurtscherLuca Zangrandi

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