Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring.
Maternal obesity may affect the child's long-term development and health, increasing the risk of diabetes and metabolic syndrome. In addition to the metabolic and endocrine systems, recent reports have indicated that maternal obesity also modulates neural circuit formation in the offspring. However, this not yet been fully investigated. Here, we examined the effect of diet-induced maternal obesity on hippocampal development and function in the mouse offspring. Adult female mice were fed either a normal diet (ND, 4% fat) or a high-fat diet (HFD, 32% fat) before mating and throughout pregnancy and lactation. After weaning, all offspring were fed with a normal diet. We found that HFD offspring showed increased lipid peroxidation in the hippocampus during early postnatal development. HFD offspring had less brain-derived neurotrophic factor (BDNF) in the hippocampus than ND offspring. BDNF has been shown to play crucial roles in neuronal differentiation, plasticity and hippocampus-dependent cognitive functions such as spatial learning and memory. Using retroviral labeling, we demonstrated that dendritic arborization of new hippocampal neurons was impaired in the young HFD offspring. Finally, we evaluated cognitive function in these offspring using hippocampus-dependent behavioral tasks. The Barnes maze test demonstrated that HFD offspring showed impaired acquisition of spatial learning in the young but not adult period. This study, using a mouse model, indicates that diet-induced maternal obesity impairs hippocampal BDNF production and spatial cognitive function in young offspring, possibly due to their metabolic and oxidative changes.
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yusuke
Y
Tozuka
Mami
M
Kumon
Etsuko
E
Wada
Masafumi
M
Onodera
Hideki
H
Mochizuki
Keiji
K
Wada
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004041:Dietary Fats; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000378:metabolism* / Q000523:psychology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000523:psychology*; D012190:Retroviridae / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D004041:Dietary Fats