CONICET | Buscador de Institutos y Recursos Humanos

Evidence shows that there is significant heterogeneity in astrocytes, regarding morphology, gene expression and function. In this work, we investigated the difference between astrocytes from two areas involved in Huntington disease (HD): the striatum and the cortex. We have previously demonstrated that BDNF exerts protective and antioxidant effects on astrocytes treated with 3-nitropropionic acid (3-NP), a toxin widely use as an in vitro model of HD. Now we determined TrkB expression on cortical and striatal astrocytes treated with or without BDNF + 3-NP. We have showed before that astrocytes in culture do not express TrkB-FL protein, therefore we measured the TrkB-T1 protein expression assessed by Western blot analysis. BDNF increases the protein expression of TrkB-T1 in cortical astrocytes. 3-NP decreases the protein level of this receptor but in presence of BDNF this effect is not observed. BDNF also increases the protein level of pERK. We found that 3-NP decreases ERK activation indicating that TrkB function is impaired by 3-NP. In Astrocytes treated with BDNF+3-NP, ERK activation persists. As regards neuroprotection, we used cortical and striatal astrocyte conditioned medium (ACM) to treat ST14A-Q120, a cell line derived from embryonic rat striatal cells which express N-terminal fragment of mutant human Htt with a 120 glutamine region (120 CAG repeats). ACM from striatal astrocytes treated with BDNF protects ST14A-Q120 from 3-NP induced death where as ACM from cortex did not modify 3-NP effects. These results suggest than only astrocytes treated with BDNF from the striatum secrete soluble neuroprotective factors. Furthermore, ACM from 3-NP treated striatal or cortex astrocytes induced death of ST14a-Q120. Only ACM from 3-NP+BDNF treated striatal astrocytes decreased ST14a-Q120 death increasing viability of ST14a-Q120 cells compared to ACM 3-NP treated astrocytes. A better understanding of the heterogeneity of astrocytes would be helpful to elucidate how these cells perform their functions and how their malfunction can contribute to neurodegenerative disease.