Original Research ARTICLE
Brain-derived neurotrophic factor (BDNF) role in cannabinoid-mediated neurogenesis
- 1Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal
- 2Instituto de Medicina Molecular (IMM), Portugal
The adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown.
We now used SVZ and DG neurosphere cultures from early (P1-3) postnatal rats to study the CB1R and CB2R crosstalk with BDNF in modulating neurogenesis. BDNF promoted an increase in SVZ and DG stemness and cell proliferation, an effect often blocked by a CB2R selective antagonist. CB2R selective activation promoted an increase in DG multipotency, which was inhibited by the presence of a BDNF scavenger. CB1R activation induced an increase in SVZ and DG cell proliferation, being both effects dependent on BDNF. Furthermore, SVZ and DG neuronal differentiation was facilitated by CB1R and/or CB2R activation and this effect was blocked by sequestering endogenous BDNF. Conversely, BDNF promoted neuronal differentiation, an effect abrogated in SVZ cells by CB1R or CB2R blockade while in DG cells it was inhibited by CB2R blockade.
We conclude that endogenous BDNF is crucial for the cannabinoid-mediated effects on SVZ and DG neurogenesis. On the other hand, cannabinoid receptor signaling is also determinant for BDNF actions upon neurogenesis. These findings provide support for an interaction between BDNF and endocannabinoid signaling to control neurogenesis at distinct levels, further contributing to highlight novel mechanisms in the emerging field of brain repair.
Keywords: postnatal neurogenesis, subventricular zone (SVZ), Dentate Gyrus, Cannabinoid receptor, BDNF (brain derived neurotrophic factor)
Received: 31 Jul 2018;
Accepted: 05 Nov 2018.
Edited by:Josef Bischofberger, Universität Basel, Switzerland
Reviewed by:Alex Dranovsky, Columbia University, United States
Jorge Matias-Guiu, Complutense University of Madrid, Spain
Copyright: © 2018 Ferreira, Ribeiro, Rodrigues, Sebastiao and Xapelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Sara Xapelli, Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisbon, 1649-028, Portugal, firstname.lastname@example.org