AI Article Synopsis
- NMDA receptor activity is linked to excitotoxicity, a key factor in Huntington's disease (HD) progression.
- The neurotrophin BDNF influences NMDA receptors and interacts with adenosine A2ARs, affecting their behavior in HD models.
- BDNF showed potential to enhance NMDA effects in healthy mice but provided protection against NMDA toxicity in R6/2 HD mice, a benefit which was abolished when A2ARs were blocked.
Article Abstract
NMDA receptor-mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin brain-derived neurotrophic factor (BDNF), which is also highly involved in HD and whose effects are modulated by adenosine A2 ARs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF toward NMDA-induced effects in HD models, and the possible involvement of A2ARs. 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 wild-type, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A2 AR 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 A2 AR ligands in HD.
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| http://dx.doi.org/10.1111/jnc.12177 | DOI Listing |
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