Brain-derived neurotrophic factor (BDNF) prevents 3-nitropropionic acid-induced death in Huntington?s disease neuronal striatal cell model

SABA JULIETA; CARNIGLIA LILA; CARUSO CARLA; RAMÍREZ DELIA; LASAGA MERCEDES; TURATI, JUAN; DURAND DANIELA

Mar del Plata

Congreso; XXXII Congreso Anual SAN; 2017

SAN

Huntington disease (HD) is an autosomal dominant disease caused by mutation of the huntingtin (Htt) gene leading to expanded polyglutamine repeats in mutant Htt (mHtt) that promotes oxidative stress, mitochondrial dysfunction, neurotoxicity, and motor and behavioral changes. Also, impairment in BDNF synthesis is considered determinant in the pathogenesis of HD. We have previously shown that BDNF prevents astrocyte apoptosis induced by 3-nitropropionic acid (3-NP), a toxin that causes mitochondrial dysfunction and oxidative stress as it occurs in HD. Now, we studied BDNF effects on HD neuronal striatal cell model ST14a-Q120 (Q120), which express human mHtt with 120 glutamine repeats and ST14a-Q15 (Q15) which express normal human Htt with 15 glutamine repeats. We detected mHtt aggregates in Q120 cells treated with 3-NP which were undetectable by coincubation with BDNF. Q120 cells were more susceptible to 3-NP-induced cell death than Q15. BDNF had a significant protective effect on 3-NP-induced death of Q120 cells while it was ineffective on Q15 cells. Finally, in agreement with this latest result, we found that ACM from 24h BDNF-treated astrocytes, reduced the decrease in viability induced by 3-NP in Q120 but not in Q15 cells. Altogether data suggest that BDNF protects Q120 cells but not Q15 cells from 3-NP actions, and that astrocytes may contribute to neuroprotection by BDNF. Understanding BDNF protective mechanisms may help find new targets for treating neurodegeneration.