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

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

Buenos Aires

Simposio; The role of glia in health and disease of the nervous system: clinical and basic science walking together; 2017

ISN, IBRO

Huntington disease (HD) is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that promotes oxidative stress, mitochondrial dysfunction, neurotoxicity, and motor and behavioral changes. Also, as in many neurodegenerative diseases, an impairment in the synthesis of BDNF 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. We have also found that astrocyte conditioned medium (ACM) from 24h BDNF-treated astrocytes, blocked the decrease in PC12 neuron viability induced by 3-NP. Therefore, we studied BDNF effects on a striatal cell line Huntington´s disease model ST14a Q120 , which express human mHtt with 120 glutamine repeats and wild-type ST14a Q15 which express human Htt with 15 glutamine repeats as a control. In order to investigate the difference between both cell types we examined by immunofluorescence analysis the presence of Htt. We detected mHtt inclusion in Q120 treated with 3-NP meanwhile this aggregation seems undetectable in presence of BDNF. Striatal Q120 viability is more susceptible to 3-NP than Q15. Furtheremore, BDNF had a significant protective effect on 3-NP induced death while it was ineffective on control Q15 cells. Finally, in agreement with this latest result, we found that astrocyte condition medium from 24h BDNF-treated astrocytes, reduced the decrease in viability induced by 3-NP in Q120 but not in Q15 cells. Understanding BDNF protective mechanisms may help develop new strategies for treating neurodegenerative diseases.