Exploring the role of serotonin depletion in the BDNF pathway and the ability for pattern separation

DIAZ, SILVINA LAURA; STEFANI, KAREN MELANY; FOLTRAN, ROCÍO BEATRIZ

Bordeaux

Congreso; 4th Eurogenesis meeting; 2019

Inserm

Modulation of serotonergic neurotransmission has revealed as an exciting tool to study the process of neurogenesis in the adult hippocampus (HC). Chronic inhibition of tryptophan hydroxylase by para-chlorophenylalanine (PCPA), induces a decrease of serotonin (5-HT) levels and promotes survival of newborn neurons in the HC. We analyzed the molecular pathway of the Brain derived neurotrophin factor (BDNF) in mice treated with PCPA. C57BL/6J male 6-week old mice were treated during 8 weeks by giving aprox PCPA 250mg/kg/day inside yeast and jelly cubes, an oral administration we set up. Control group received cubes without PCPA. After treatments, proteins were extracted from hippocampi and levels of BDNF, TrkB, p75, proBDNF, BCL2 were quantified by Western Blot. P75 was found to be enhanced after PCPA treatment, and a tendency for a decrease was found for TrkB and proBDNF. When animals were administered a 5-HT1A receptor agonist for 1week after 4 weeks of PCPA, a protocol that reestablishes the neurogenical phenotype, an increase was observed for proBDNF and p75. As we intend to study the role of the new neurons in the HC, we also set up the Object Pattern Separation (OPS), a test recently developed that allows finding subtle differences compared to classical tests. Although no significance was achieved, hyposerotonergic mice showed a tendency to a minor discrimination index. Our results show a clear participation of the BDNF pathway in the regulation of neurogenesis induced by PCPA, but the lack of improved performance in the OPS casts doubts about the functional role of these newborn neurons.