We report that BDNF and selective tyrosine kinase receptor B (TrkB) agonist 7,8-dihydroxyflavone (DHF) activated the TrkB receptor to facilitate two forms of eCB-mediated synaptic depression, depolarization-induced suppression of inhibition (DSI), and long-term depression (I-LTD) of IPSCs in ventral tegmental area dopamine neurons in mouse midbrain slices.
Genetic variation associated with reduced function in the CREB1-BDNF-NTRK2 pathway has multiple, sometimes opposing, influences on risk mechanisms of depression, but almost all the SNPs studied amplified the effect of childhood adversity.
This study examines the main effects of single loci and multilocus interactions to test the hypothesis that the BDNF and NTRK2 genes may contribute to the etiology of geriatric depression independently and/or through complex interactions.
After controlling for age, gender and baseline 21-item Hamilton Depression Rating Scale (HAM-D21) score, as well as correcting for multiple testing, the relative reduction of HAM-D21 score remained significantly associated with two NTRK2-coding SNPs (rs2289657 and rs56142442) and the haplotype CAG at rs2289658 (splice site), rs2289657 and rs2289656.