A tale of two genes: Reelin and Bdnf

Abstract

BDNF is a survival factor for the Cajal-Retzius cells in the marginal zone, which are an important source of Reelin in the neocortex. BDNF is also a negative regulator of Reelin expression in both Cajal-Retzius cells and GABAergic cells in the cortical plate. BDNF and Reelin act in parallel to regulate many processes during neural development and maintenance, including cell migration and neural plasticity. Frequently, BDNF and Reelin have opposite influences on the processes they regulate, suggesting that BDNF-induced downregulation of Reelin is involved. Reelin is an important regulator of neural migration during neocortex formation. BDNF seems to influence this process both directly and indirectly via regulation of Reelin expression. Moreover, epileptic seizures increase BDNF levels while decreasing Reelin levels, and BDNF and Reelin seem to have opposite roles in mediating the effects of the seizures. Mental disorders, in particular schizophrenia, involve alterations in BDNF and Reelin expression. Again, the changes are mainly opposite, and a negative regulation of Reelin by BDNF has been suggested. In contrast, hippocampal LTP is promoted by both Reelin and BDNF signaling. Finally, there is overlap in the epigenetic regulation and signaling pathways of BDNF and Reelin.