Local synthesis of brain derived neurotrophic factor (BDNF) in the striatal cholinergic interneurons of the murine model of Huntington’s disease

Introduction: BDNF is essential for the survival of striatum and is dramatically reduced in Huntington disease. Many studies have shown that striatum does not synthetize BDNF, which is anterogradely transported from the cortex. In a previous study, we had shown the presence of BDNF protein into striatal cholinergic neurons of an excitotoxic rat model of HD, where the corticostriatal projectons were abolished. Materials and methods: In order to investigate the presence of BDNF mRNA, we fluorescently labeled cholinergic neurons from dissociated striata of of R6/2 mice and wil-dtipe littermates at different time-points. Moreover, we performed single-cell RT PCR on electrophysiologically identified cholinergic interneurons and in-situ hybridization to label BDNF mRNA in the mouse brain slices. Results: 1) BDNF mRNA contained in the cholinergic neurons corresponds to an isoform that is distinct from the one contained in the projection neurons. 2)Cholinergic neurons maintain their BDNF mRNA throughout the stages of the disease, whereas mRNA levels of BDNF decrease in the spiny neurons in R6/2 mice. Discussion: The cholinergic interneurons subpopulation is the most resistant of the striatum not only in HD, but also in ischemia and other neurodegenerative conditions. The intrinsic ability of synthesis of an important trophic factor such as BDNF, that we demonstrate here, contributes to explain such reduced vulnerability.