title: Abnormal instability, excess density, and aberrant morphology of dendritic spines in prenatally testosterone-exposed mice.
abstract: Fetal brain development is programmed by the maternal intrauterine environment, and disturbance of the in utero environment leads to persisting deficits in brain functions of the offspring. Testosterone is an intrauterine environmental factor, and plays significant roles in fetal development. From human and animal model studies, it has been suggested that increased intrauterine testosterone concentration triggers subsequent autistic-like behavior of the offspring; however, the effects of maternal excess testosterone on synaptic development of the offspring remain unknown. In the present study, we employed prenatally testosterone-exposed mice, and by using in vivo two-photon imaging, we analyzed the dynamics, density, and morphology of the dendritic spine, an excitatory postsynaptic structure. We found that the offspring from testosterone-treated dams showed abnormal synaptic instability persisting into young adulthood, whereas dendritic spines in control mice became stabilized with normal synaptic maturation. In prenatally testosterone-exposed mice, the density of dendritic spines was excessively increased, and their morphology was abnormal. These results suggest that prenatally testosterone-exposed mice may have deficits in synaptic development, and furthermore that the observed pathological features of their dendritic spines may be the cause of the synaptic pathogenesis in prenatally testosterone-exposed mice.
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. Electronic address: hatanaka@ncnp.go.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 / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013739:Testosterone / Q000008:administration & dosage*
chemical_list: D013739:Testosterone
keywords: Autism; Dendritic spine; In vivo two-photon imaging; Maternal environment; Polycystic ovary syndrome; Testosterone