Contribution of the brain-derived neurotrophic factor and neurometabolites to the motor performance.

Individual motor performance ability is affected by various factors. Although the key factor has not yet completely been elucidated, the brain-derived neurotrophic factor (BDNF) genotype as well as neurometabolites may become contibuting factors depending on the learning stage. We investigated the effects of the Met allele of the BDNF gene and those of the neurometabolites on visuomotor learning. In total, 43 healthy participants performed a visuomotor learning task consisting of 10 blocks using the right index finger (Val66Val, n = 15; Val66Met, n = 15; and Met66Met, n = 13). Glutamate plus glutamine (Glx) concentrations in the primary motor cortex, primary somatosensory cortex (S1), and cerebellum were evaluated using 3-T magnetic resonance spectroscopy in 19 participants who participated in the visuomotor learning task. For the learning stage, the task error (i.e., learning ability) was significantly smaller in the Met66Met group compared with that observed in the remaining groups, irrespective of the learning stage (all p values < 0.003). A significant difference was observed between the Val66Val and Met66Met groups in the learning slope (i.e., learning speed) in the early learning stage (p = 0.048) but not in the late learning stage (all p values> 0.54). Moreover, positive correlations were detected between the learning slope and Glx concentrations in S1 only in the early learning stage (r = 0.579, p = 0.009). The BDNF genotype and Glx concentrations in S1 partially contribute to interindividual variability on learning speed in the early learning stage.

Large-scale analysis of glucocorticoid target genes in rat hypothalamus.

Insufficient glucocorticoid (GC) signaling is frequently observed in major depressive disorder (MDD). Since emotional and behavioral symptoms are often accompanied by disturbances in hypothalamic systems, GC insufficiency in this region is regarded as important in the pathogenesis of MDD. In this study, 22 early GC-responsive genes comprising 15 up-regulated and 7 down-regulated genes in rat hypothalamus were identified as being regulated at least two-fold by dexamethasone using microarray with 22 599 unique transcripts. Among these 22 genes, five of which are novel GC-responsive genes, the expression patterns of sgk, bcl6, pdk4, and plekhf1 were examined in vitro in detail, and GC-responsive regions were identified only within the promoter of sgk. This suggests that glucocorticoid response element-independent pathways also play a critical role in early GC-response in hypothalamus. Considering that a number of these GC-responsive genes are candidate neuronal regulators, this gene list should be useful in clarifying the relationship between GC insufficiency and the pathogenesis of MDD.