Neurochemistry and Neuropharmacology
Author: Rocío Beatriz Foltran Foltran | email: rbfoltran@conicet.gov.ar
Rocío B Foltran 1°, Karen M Stefani 1°, Silvina L Diaz 1°
1° Inst. de Biología Celular y Neurociencias. UBA-CONICET. Buenos Aires, Argentina
Modulation of serotonergic neurotransmission has revealed as an exciting tool to study the process of neurogenesis in the adult hippocampus (HC). Paradoxically, different models of mice with altered levels of serotonin (5-HT), both increased or depleted, show enhanced survival of newborn neurons in the HC. Were interested in understanding the role of the brain derived neurotrophin factor (BDNF) signaling pathway in the link between neurogenesis and 5-HT. To study this, we administered ANA-12, an antagonist of the BDNF receptor TrkB, to mice chronically treated with a serotonergic antidepressant. We conducted the Object Pattern Separation (OPS) task, since it has been reported that mice performance in this test depends on newborn neurons in the HC. We werent able to find significant changes in a pattern separation test. However, ANA-12 prevented the increase in newborn neurons in the HC of antidepressant-treated mice. On the other hand, in Pet1-/- mice most of serotonergic neurons do not differentiate, leading to an 80% depletion of serotonin. In the OPS test, these mice with increased neuronal survival showed a better discrimination index than control mice. On the other hand, when they were treated with ANA-12, Pet1-/- mice presented a decreased performance in the task. Our results show that the BDNF/TrkB pathway could be involved in the enhancement of survival of newborn neurons in the HC when 5-HT is altered, with differential effects on behavioral patterns.