Publication Date:
2013-02-01
Description:
N-methyl-D-aspartic acid (NMDA) receptor-mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin BDNF, which is also highly involved in HD and whose effects are modulated by adenosine A 2 A Rs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF towards NMDA-induced effects in HD models, and the possible involvement of A 2 A Rs. In corticostriatal slices from wild-type mice and age-matched symptomatic R6/2 mice (a model of HD), NMDA application (75 μM) induced a transient or a permanent (i.e. toxic) reduction of field potential amplitude, respectively. BDNF (10 ng/ml) potentiated NMDA effects in wt, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A 2 A R blockade. The protective effect of BDNF against NMDA-induced toxicity was reproduced in a cellular model of HD. These findings may have very important implications for the neuroprotective potential of BDNF and A 2 A R ligands in HD. © 2013 International Society for Neurochemistry, J. Neurochem. (2013) 10.1111/jnc.12177
Print ISSN:
0022-3042
Electronic ISSN:
1471-4159
Topics:
Medicine
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