Biochemical, biometrical and behavioral changes in male offspring of sleep-deprived mice.
Epidemiological and experimental studies suggest a high prevalence of cognitive impairment and social behavior deficits in adolescents and adults that have experienced prenatal exposure to adverse conditions. This study investigated whether sleep deprivation during the pre-implantation stage of development alters the physiological, behavioral and oxidative metabolic processes in adult male mouse offspring. One group of dams was continuously sleep-deprived using the platform technique from gestational days 0 to 3 (PSD 72). Three additional groups were sleep-deprived by gentle handling for 6h on gestational days 1 (GH 1), 2 (GH 2) or 3 (GH 3). After sleep deprivation, homocysteine, cysteine, corticosterone, estrogen and progesterone concentrations were measured from the experimental mothers and time-matched controls. The sizes and weights of the male pups were measured at various stages throughout the experiment. At PND 90, behavioral (Activity Box and Elevated Plus Maze) and biochemical parameters were assessed. The dams' plasma progesterone concentrations decreased in the PSD 72 group, and the levels of plasma estradiol increased in GH 2. Corticosterone levels were found to increase after all sleep-deprivation procedures. Homocysteine concentrations increased in the GH 2 but decreased in the PSD 72 group. The offspring of GH 1 mothers exhibited decreased superoxide dismutase activity. Exposure to sleep deprivation had a long-lasting impact on tissue weight; in particular, there was a decrease in hemilateral epididymal fat weight in mature animals from the PSD 72 group. Although some of the alterations observed in the mothers (elevated estrogen and corticosterone levels and decreased progesterone) might have played a role in the permanent alterations in the adult offspring, they were not the main cause. The homocysteine changes detected in the sleep-deprived dams may contribute to redox changes, controlling gene expression and shaping epigenetic development.
Calegare
Bruno Frederico Aguilar
BF
Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
Fernandes
Leandro
L
Tufik
Sergio
S
D'Almeida
Vânia
V
D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D003545:Cysteine / Q000097:blood; D047108:Embryonic Development; D004958:Estradiol / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D008098:Litter Size; D008297:Male; D018782:Maze Learning; D051379:Mice; D009043:Motor Activity; D009929:Organ Size; D011247:Pregnancy; D011255:Pregnancy Maintenance; D011374:Progesterone / Q000097:blood; D012744:Sex Ratio; D012892:Sleep Deprivation / Q000378:metabolism* / Q000523:psychology*; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors
D006710:Homocysteine; D011374:Progesterone; D004958:Estradiol; D013482:Superoxide Dismutase; D003545:Cysteine; D003345:Corticosterone