Perinatal alterations of thyroid hormones and behaviour in adult rats

Darbra, Sònia; Balada, Ferran; Garau, A; Gatell, P.; Sala, J. J.; Martí-Carbonell, Maria Assumpció

doi:10.1016/0166-4328(94)00166-d

Cited by 23 publications

(24 citation statements)

References 35 publications

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“…The rationale for the prenatal T 4 administration was that some of the deleterious effects of maternal hypothyroidism on the offspring thyroid function can be reversed by maternal thyroid hormone replacement (8,11,42). However, T 4 administration to the alcoholconsuming mother did not reverse the hypothyroid state of the FAE offspring in this study.…”

Section: Discussionmentioning

confidence: 57%

“…Beginning on G8, the T4 dams received thyroxine (30 g/ml, Sigma Chemical, St. Louis, MO) in the PF or E liquid diet or in the drinking water for the CϩT4 mothers until G18. This thyroid hormone treatment has been shown to alter behavior in adult offspring (11). The average daily diet consumption was 101 Ϯ 4.7 ml, so the dams received ϳ3 mg of T4 per day.…”

Section: Methodsmentioning

confidence: 99%

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Prenatal programming of adult thyroid function by alcohol and thyroid hormones

Wilcoxon

Redei

2004

American Journal of Physiology-Endocrinology and Metabolism

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Increasing evidence associates environmental challenges early in life with permanent alterations of physiological functions in adulthood. These changes in fetal environment can trigger physiological adaptations by the fetus, called fetal programming, which may be beneficial before birth but permanently influence the physiology of the organism. In this study, we investigated the potential connection between alcohol-induced decreased maternal thyroid function and the hypothalamic-pituitary-thyroid (HPT) function of adult rat offspring. Plasma 3,5,3'-triiodothyronine (T(3)), thyroxine (T(4)), and thyroid-stimulating hormone (TSH) levels were decreased in alcohol-consuming (E) dams on gestational day 21 compared with ad libitum- (C) and pair-fed (PF) controls. No significant differences were found in HPT function in young offspring (3 wk of age) between diet groups. However, adult fetal alcohol-exposed (FAE) offspring had significantly decreased levels of T(3) along with elevated TSH compared with control offspring. T(4) administration to the mother did not normalize the hypothyroid state of the adult FAE offspring. Interestingly, administration of T(4) to control pregnant dams decreased plasma T(3) of the adult female offspring only, whereas T(4) together with maternal alcohol consumption or pair-feeding led to decreased TSH and T(4) in the adult female offspring. Our results suggest that ethanol consumption and T(4) administration alter maternal HPT function, leading to prenatally programmed permanent alterations in the thyroid function of the adult offspring.

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Section: Discussionmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Prenatal programming of adult thyroid function by alcohol and thyroid hormones

Wilcoxon

Redei

2004

American Journal of Physiology-Endocrinology and Metabolism

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“…The average daily diet consumption was 10174.7 ml, so the dams received approximately 3 mg of thyroxine per day. This thyroid hormone treatment paradigm for pregnant dams, which has been shown to alter behavior in adult offspring, 44 significantly increased maternal plasma T4, and decreased plasma TSH levels compared to the hormone levels measured in dams on the same diet without thyroxine. 31 Administration of T4 to the pregnant dams did not reverse the body weight decrease seen in the ethanol-consuming dams compared to both PF and controls, nor did it eliminate the difference between PF and control dams.…”

Section: Methodsmentioning

confidence: 92%

Behavioral deficits associated with fetal alcohol exposure are reversed by prenatal thyroid hormone treatment: a role for maternal thyroid hormone deficiency in FAE

et al. 2005

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Children prenatally exposed to alcohol typically exhibit behavioral abnormalities, including hyperactivity, learning deficits, and an increased prevalence of depression. Similar impairments are found in children of hypothyroid mothers, and we have shown that alcohol-consuming rat dams have suppressed hypothalamic-pituitary-thyroid (HPT) function. Therefore, we hypothesized that suppressed maternal thyroid hormonal milieu may contribute to the deleterious consequences of prenatal alcohol exposure. We aimed first to confirm and then to reverse the behavioral deficits in the fetal alcohol exposed (FAE) rat offspring by administration of thyroxine (T4) to the alcohol-consuming dams. Adult offspring prenatally exposed to ethanol (FAE; 35% ethanol-derived calories), pair-fed (PF) or control (C) diets were tested in the Morris water maze (MWM), the forced swim test (FST), and the open field test (OFT) to assess spatial learning, depressive behavior, and exploratory behavior/anxiety, respectively. Adult FAE offspring took longer to locate a hidden platform in the MWM and showed increased depressive behavior in the FST both of which were reversed by administration of T4 to the alcohol-consuming mother. We found sex and brain regionspecific alterations in expression of genes involved in these behaviors in FAE adult offspring. Specifically, decreased hippocampal GAP-43 mRNA levels in adult FAE females and decreased glucocorticoid receptor (GR) expression in the amygdala of male and female FAE offspring were observed. The decreased mRNA levels of GAP-43 and GR were normalized by T4 treatment to the alcohol-consuming mother. Our results suggest that the suppressed HPT function of the alcohol-consuming mother contributes to the behavioral and cognitive dysfunctions observed in the offspring. Prenatal alcohol exposure has long-term developmental consequences, 1-3 and in humans alcohol is recognized as a teratogen leading to long-lasting CNS dysfunctions. 4 Specifically, patients with fetal alcohol exposure (FAE) have marked cognitive deficits, including difficulty focusing and sustaining attention, 5 and place learning deficits in a virtual Morris water task. 6 Attention deficit hyperactivity disorder (ADHD) is frequently diagnosed in FAE children. These neurocognitive and behavioral characteristics differ between FAE children and those with a primary diagnosis of ADHD, as FAE children have difficulties primarily in the encoding and retrieval of information. 7 A significantly increased prevalence of depression is also found in children 8 and adults 9 prenatally exposed to alcohol. It is important to note that, in contrast to the higher female prevalence of depressive disorders in the general population, the rate of depression found in adults with prenatal alcohol exposure was nearly equal among men and women. 9 Fetal alcohol effects qualitatively similar to those described in children with a history of gestational alcohol exposure have been detected with animal models. 10 Cognitive deficits have been found in FAE animal models...

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“…As shown in the open field test, increased level of endocrine hormones did not significantly disrupt the voluntary behavior of the animals. Thus, it was established that rats given high doses of thyroxine had greater disruption of behavior than learning [6]. Oitzl et al [11] found that both single high doses of corticosterone (1000 lag/kg) and chronic administration of low doses (50 Ixg/kg) for seven days led to increases in behavioral activity in intact rats relative to an object in the center of the field.…”

Section: Discussionmentioning

confidence: 99%

The effects of the hormones of peripheral endocrine glands on the processes of behavior, learning, and memory

Fedotova

2000

Neurosci Behav Physiol

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The effects of systemic administration of thyroid, adrenal cortex, and sex hormones on learning ability, memory trace retention, and behavior were compared in male rats. These studies showed that thyroid, corticosteroid, and sex hormones had no effect on passive learning. Excess quantities of sex hormones disrupted active learning and subsequent reproduction of received information; an excess of thyroid hormone improved the acquisition and retention of the active avoidance habit. Increases in the levels of adrenal cortex hormones worsened active learning and the retention of memory traces, and also increased the level of behavioral activity.

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Perinatal alterations of thyroid hormones and behaviour in adult rats

Cited by 23 publications

References 35 publications

Prenatal programming of adult thyroid function by alcohol and thyroid hormones

Prenatal programming of adult thyroid function by alcohol and thyroid hormones

Behavioral deficits associated with fetal alcohol exposure are reversed by prenatal thyroid hormone treatment: a role for maternal thyroid hormone deficiency in FAE

The effects of the hormones of peripheral endocrine glands on the processes of behavior, learning, and memory

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