title: Maternal high-fat diet leads to persistent synaptic instability in mouse offspring via oxidative stress during lactation.
abstract: Maternal obesity has negative effects on the neurodevelopment of the offspring. Pups from high-fat diet (HFD)-fed mice exhibit peroxidized lipid accumulations in the brain and behavioral impairments. However, the synaptic basis of maternal HFD-induced brain dysfunction in offspring remains unclear. In the present study, we focused on the dynamics and morphology of postsynaptic dendritic spines and filopodia in the offspring of HFD-fed mouse dams, using in vivo two-photon imaging, chosen because of the involvement of peripheral organs and non-neuronal cells in the abnormal metabolic state. We observed instability of dendritic spines and filopodia in the cerebral cortex of offspring from HFD-fed dams. Interestingly, the synaptic instability persisted into adulthood with a lower spine density even when the offspring were fed with a normal diet after weaning. HFD-fed offspring from HFD-fed dams showed a severe disruption of dendritic spines. Synaptic instability and loss of spines were caused even by HFD exposure exclusively during lactation. The treatment of ascorbic acid, an antioxidant, during lactation ameliorated the synaptic impairments. These results suggest that maternal obesity leads to persistent synaptic impairments in the offspring, which may be associated with behavioral deficits in adulthood, and that these synaptic deficits may be due to oxidative stress from peroxidized lipid accumulations during the lactation period.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan; Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto City 606-8507, Japan. Electronic address: hatanaka@kuhp.kyoto-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. Electronic address: kabuta@ncnp.go.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects* / Q000639:trends; D005260:Female; D007774:Lactation / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
keywords: Antioxidant; Dendritic spine; High-fat diet; In vivo two-photon imaging; Lactation; Maternal environment