Brain derived neurotrophic factor (BDNF) plays a crucial role in regulating synaptic plasticity and neuronal architecture through complex downstream signalling cascades mediated via receptor Tyrosine Kinase B (TrkB). Impaired BDNF/TrkB signalling has been associated with several neurological disorders. A treatment with Fingolimod has been shown in vitro and in vivo to promote BDNF synthesis and release and exert BDNF-dependent neuroprotection. Estrogens are a group of steroid sex hormones synthesised by neurons and astrocytes predominantly in females. In the hippocampus, estradiol plays a crucial role in synaptic plasticity and regulates the expression of several crucial genes, including BDNF. Moreover, differences in the amount of BDNF mRNA were shown in male and female mice. The above studies suggest the possibility of a sex-specific response to the BDNF-inducing drug Fingolimod.We investigated the effect of Fingolimod on neuronal architecture in male- and female-derived mouse hippocampal pyramidal neurons. A 24-hour application of Fingolimod to mature organotypic hippocampal cultures, showed increased dendritic spine density in both sexes, however females exhibited a relatively higher response post treatment. Co-application of Fingolimod with TrkB-receptor bodies (Trkb-Fc) revealed a BDNF-dependent effect primarily in males. Moreover, male-derived neurons displayed higher BDNF protein expression. These results indicate that mouse neurons respond to Fingolimod in a sex-specific manner, with female neurons showing a higher sensitivity and males a stronger BDNF-dependency. Ongoing experiments investigate the sex-specific BDNF-dependent effect of Fingolimod on long term potentiation (LTP).This work is supported by a grant from the Deutsche Forschungsgemeinshaft to Martin Korte and Marta Zagrebelsky