Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice.
Diabetes may adversely affect cognitive function, but the underlying mechanisms are unknown. To investigate whether manipulations that enhance neurotrophin levels will also restore neuronal structure and function in diabetes, we examined the effects of wheel running and dietary energy restriction on hippocampal neuron morphology and brain-derived neurotrophic factor (BDNF) levels in db/db mice, a model of insulin resistant diabetes. Running wheel activity, caloric restriction, or the combination of the two treatments increased levels of BDNF in the hippocampus of db/db mice. Enhancement of hippocampal BDNF was accompanied by increases in dendritic spine density on the secondary and tertiary dendrites of dentate granule neurons. These studies suggest that diabetes exerts detrimental effects on hippocampal structure, and that this state can be attenuated by increasing energy expenditure and decreasing energy intake.
Stranahan
Alexis M
AM
Psychology department, Princeton University, Princeton, New Jersey, USA.
Lee
Kim
K
Martin
Bronwen
B
Maudsley
Stuart
S
Golden
Erin
E
Cutler
Roy G
RG
Mattson
Mark P
MP
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D031204:Caloric Restriction; D049229:Dendritic Spines / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004038:Diet, Reducing; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D054411:Receptors, Leptin / Q000235:genetics; D012420:Running / Q000502:physiology; D014836:Volition
D019208:Brain-Derived Neurotrophic Factor; D054411:Receptors, Leptin; C515447:leptin receptor, mouse