Dietary restriction changes behaviours in brain-derived neurotrophic factor heterozygous mice: role of serotonergic system

Accumulating evidence has suggested that brain-derived neurotrophic factor (BDNF) plays a role in eating behaviours, and that BDNF-heterozygous (+/-) mice exhibit abnormal behaviours (e.g. obesity, anxiety and aggression). The present study was undertaken to determine whether or not dietary restriction (DR) alters the behaviours in BDNF+/- mice, as DR has been shown to exert a number of beneficial effects on the brain. Eight-week-old male wild-type (+/+) and BDNF+/- mice were divided into two groups, ad libitum (AL) diet group and DR group, for 16 weeks. After carrying out a behavioural evaluation, we determined the BDNF mRNA levels, as well as mRNA levels for subtypes (5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C) of the 5-HT receptor and 5-HT transporter (5-HTT), protein levels of BDNF and concentrations of 5-HT and 5-HIAA in the hypothalamus, hippocampus and frontal cortex. DR significantly ameliorated behaviours including obesity, anxiety and aggression in BDNF+/- mice. The concentrations of 5-HT and 5-HIAA in the frontal cortex, and 5-HT in the hippocampus, of BDNF+/- mice were significantly lower than those of wild-type mice. Interestingly, DR significantly increased the levels of 5-HT and 5-HIAA in the frontal cortex of BDNF+/- mice. These findings suggest that DR may alter the behaviours in BDNF+/- mice, and that the 5-HT system may be implicated in the beneficial effects of DR on these behaviours.