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-HT(1A), 5-HT(1B), 5-HT(2A) and 5-HT(2C)) 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.
Koizumi
Hiroki
H
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Hashimoto
Kenji
K
Iyo
Masaomi
M
D000374:Aggression / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D004435:Eating / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology*; D006579:Heterozygote; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000503:physiopathology / Q000523:psychology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid