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Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats.

ABSTRACT: The neurodevelopmental fetal alcohol spectrum disorder (FASD) is characterized by cognitive and behavioral deficits in the offspring. Conferring the deficits to the next generation would increase overall FASD disease burden and prevention of this transmission could be highly significant. Prior studies showed the reversal of these behavioral deficits by low dose thyroxine (T4) supplementation to the ethanol-consuming mothers. Here we aim to identify whether prenatal ethanol (PE) exposure impairs hippocampus-dependent learning and memory in the second-generation (F2) progeny, and whether T4 administration to the ethanol-consuming dam can prevent it. Sprague-Dawley (S) dams received control diets (ad libitum and nutritional control) or ethanol containing liquid diet with and without simultaneous T4 (0.3mg/L diet) administration. Their offspring (SS F1) were mated with naive Brown Norway (B) males and females generating the SB F2 and BS F2 progeny. Hippocampus-dependent contextual fear memory and hippocampal expression of the thyroid hormone-regulated type 3 deiodinase, (Dio3) and neurogranin (Nrgn) were assessed. SS F1 PE-exposed females and their SB F2 progeny exhibited fear memory deficits. T4 administration to the mothers of F1 females reversed these deficits. Although SS F1 PE-exposed males also experienced fear memory deficit, this was neither transmitted to their BS F2 offspring nor reversed by prenatal T4 treatment. Hippocampal Dio3 and Nrgn expression showed similar pattern of changes. Grandmaternal ethanol consumption during pregnancy affects fear memory of the matrilineal second-generation progeny. Low dose T4 supplementation prevents this process likely via altering allele-specific and total expression of Dio3 in the hippocampus.

SUBMITTER: Tunc-Ozcan E

PROVIDER: S-EPMC4902747 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats.

Tunc-Ozcan Elif E Harper Kathryn M KM Graf Evan N EN Redei Eva E EE

Hormones and behavior 20160416

The neurodevelopmental fetal alcohol spectrum disorder (FASD) is characterized by cognitive and behavioral deficits in the offspring. Conferring the deficits to the next generation would increase overall FASD disease burden and prevention of this transmission could be highly significant. Prior studies showed the reversal of these behavioral deficits by low dose thyroxine (T4) supplementation to the ethanol-consuming mothers. Here we aim to identify whether prenatal ethanol (PE) exposure impairs ...[more]

PMID: 27090562

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Project description:Matrilineal overthrows in macaque societies are rare but devastating events, often resulting in severe morbidity, mortality, and loss of individual and group fitness. The handful of documented macaque overthrows provides scant evidence to reveal the severity or longevity of reproductive consequences resulting from such violent events. We analyzed archival records from semi-free ranging rhesus monkeys, Macaca mulatta, across 6 years (55 ≤ N ≤ 107, from 2007 to 2012) during which time a matrilineal overthrow occurred (in 2009) to test the hypothesis that extremely violent interactions such as a matrilineal overthrow would significantly reduce reproductive fitness for the involved matrilines and for the troop collectively. The matrilineal overthrow resulted in a significant increase in infant loss for the population from the previous year (χ(2) = 8.117, df = 1, P = 0.004), as evidenced by the fact that in 2009, but not in other years, the proportion of infants lost was greater than the proportion of viable infants (χ(2) = 4.55, df = 1, P = 0.03). Moreover, the deposed matriline suffered 100% infant loss in 2009, a significant change from the previous year (χ(2) = 7.87, df = 1, P = 0.005) while the attacking matriline suffered 50% infant loss (also a significant change from the previous year; χ(2) = 4.44, df = 1, P = 0.035), with the uninvolved, lowest-ranking matriline showing no change in infant loss from the previous year (χ(2) = 0.008, df = 1, P = 0.93). The deposed matriline did not produce viable offspring again until 3 years later. We further found that rates of severe fighting (as indicated by the number of fight wounds requiring medical treatment) were positively correlated with infant loss across the 6 years of the study (r[s] = 0.943, P = 0.005). Our data indicate that extreme periods of intra-group conflict, such as the matrilineal overthrow, have marked short-term consequences for individual fitness, and may be extreme examples of the long-term influences that group violence exerts on the mean fitness within a primate troop.

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Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats.

Publications

Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats.

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