BDNF isoforms: a round-trip ticket between neurogenesis and serotonin?

LOPEZ STEINMETZ, LC; MAROTEAUX L; FOLTRAN, RB; DIAZ SL; HITA, F

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

FALAN-SAN

Our laboratory point to unravel how BDNF signaling can modulate the neurogenic processes in the adult hippocampus in a context of serotonin depletion. Several mice models with profound serotonin reductions display a paradoxal increase of cell survival in the hippocampus. We dissected the BDNF pathway in hyposerotonergic mice, and studied the functionality of supernumeraries newborn neurons. Hippocampal expression of BDNF isoforms, receptors, and proteases responsible for proBNF cleavage were studied. No changes in the expression of pro-BDNF, mBDNF, tPA or MMP-9 were detected in hyposerotonergic mice. However, a significant increased activation of TrkB receptor was observed. As hippocampal immature neurons play a role in pattern separation tasks, the performance of hiposerotonergic mice was studied in two different test: contextual fear-discrimination learning, and object location task. Unexpectedly, hyposerotonergic mice did not perform better than wild type mice. Indeed, the observed increased activity in the pro-neurogenic pathway mBDNF-TrkB could be linked to the pro-survival phenotype described in serotonin-depleted mice. However, it is still intriguing the lack of improvement in pattern separation paradigms. To better understand neural stem cell biology is essential for antidepressant therapies, and more exciting, it will facilitate to focus the search for new and targeted therapies using neural stem cells for a host of neurodegenerative and psychiatric disorders.