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P#228

The BDNF pathway in a model of enhanced neurogenesis via depletion of serotonin

Karen Melany Stefani

  • Ciudad Autónoma de Buenos Aires,
  • Argentina
  • Karen M. Stefani ¹
  • , Rocío B. Foltran ¹
  • , Agustina Resasco ¹
  • , Antonela Bonafina ¹
  • , Silvina L. Diaz ¹
  • 1 Instituto de Biología Celular y Neurociencia Prof. E. De Robertis, CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina

Neurotrophic factors are relevant regulators of the neurogenic process at different levels. In particular, the brain-derived neurotrophic factor, BDNF, is highly expressed in the hippocampus (HC) of rodents and participates in the control of neuronal proliferation and survival in the dentate gyrus. Likewise, serotonin (5-HT) is also involved in the regulation of neurogenesis. Indeed, both 5-HT enhancement and depletion increase neuronal survival in the HC of mice. We analyzed the protein expression of the BDNF isoforms by Western Blot, pro-and mature-BDNF, and their respective receptors p75 and TrkB, in the HC of mice chronically treated with para-chloro-phenyl-alanine (PCPA), an inhibitor of 5-HT synthesis. Increased expression of p75 receptor with decreased expression of pro-BDNF was observed after chronic PCPA. Another group of mice received a 5-HT1A receptor agonist for 1 week after 4 weeks of PCPA. This treatment reestablished the expression of pro-BDNF, and induced a higher increased of p75 receptor levels. It has been demonstrated that PCPA-treated mice have a higher number of immature neurons in the HC. Given that immature neurons participate in the pattern separation process, the object pattern separation test was conducted. A better performance of hyposerotonergic mice was not confirmed in this assay. Altogether, our results show that molecules in the BDNF signaling pathway are differentially expressed under diverse configurations of the serotonergic system.

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