Effects of experimental hypothyroidism on the development of the hypothalamo-pituitary-adrenal axis in the rat

Dakine, Nadia; Oliver, Charles; Grino, Michel

doi:10.1016/s0024-3205(00)00869-9

Cited by 22 publications

(20 citation statements)

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“…The neonatal cerebellum contains the highest levels of GC receptors in the neonatal brain (Pavlik & Buresova, 1984) which are selectively located in the EGL (Noguchi et al, 2008). In addition, as the EGL is undergoing exponential expansion and massive proliferation, it is shielded from GC stimulation by dramatically lowered free GC levels (known as the stress hyporesponsive period; Dakine et al, 2000, Pavlik & Buresova, 1984, Schmidt et al, 2003) and protection from 11β-Hydroxysteroid Dehydrogenase Type 2 (HSD2), an enzyme that efficiently metabolizes endogenous GCs in local tissue and is almost exclusively isolated in the EGL at this age (Holmes et al, 2006, Robson et al, 1998). As the neonatal rodent ages and EGL proliferation decreases, endogenous GC levels surge to adult levels (Pavlik & Buresova, 1984) and HSD2 expression concomitantly decreases (Holmes et al, 2006, Robson et al, 1998) as the EGL disintegrates now that its job of producing new neurons is over.…”

Section: Resultsmentioning

confidence: 99%

“…During normal cerebellar development, the GC system is designed such that GC stimulation in the EGL is low while this proliferative region is undergoing massive amounts of neurogenesis and growth but high when this same region decreases proliferation and disappears from the cerebellum (Buresova, 1984, Dakine et al, 2000, Holmes et al, 2006, Pavlik & Robson et al, 1998). Based on the ability of GCs to produce progenitor cell apoptosis, changes in endogenous GC stimulation may affect EGL apoptosis thereby contributing to its natural disappearance.…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis

Noguchi

Lau

Smith

et al. 2011

Neurobiology of Disease

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Glucocorticoids are used to treat respiratory dysfunction associated with premature birth but have been shown to cause neurodevelopmental deficits when used therapeutically. Recently, we established that acute glucocorticoid exposure at clinically relevant doses produces neural progenitor cell apoptosis in the external granule layer of the developing mouse cerebellum and permanent decreases in the number of cerebellar neurons. As the cerebellum naturally matures and neurogenesis is no longer needed, the external granule layer decreases proliferation and permanently disappears during the second week of life. At this same time, corticosterone (the endogenous rodent glucocorticoid) release increases and a glucocorticoid-metabolizing enzyme that protects the external granule layer against glucocorticoid receptor stimulation (11B-Hydroxysteroid-Dehydrogenase-Type 2; HSD2) naturally disappears. Here we show that HSD2 inhibition or raising corticosterone to adult physiological levels can both independently increase neural progenitor cell apoptosis in the neonatal mouse. Conversely, glucocorticoid receptor antagonism decreased natural physiological apoptosis in this same progenitor cell population suggesting endogenous glucocorticoid stimulation may regulate apoptosis in the external granule layer. We also found that glucocorticoids HSD2 can effectively metabolize generate less external granule layer apoptosis then glucocorticoids this enzyme is ineffective at breaking down. This finding may explain why glucocorticoids this enzyme can metabolize are clinically effective at treating respiratory dysfunction yet seem to produce no neurodevelopmental deficits. Finally, we demonstrate that both acute and chronic glucocorticoid exposure produces external granule layer apoptosis but without appropriate control groups this effect becomes masked. These results are discussed in terms of their implications for glucocortiocid therapy and neurodevelopment during the perinatal period.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis

Noguchi

Lau

Smith

et al. 2011

Neurobiology of Disease

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“…Neonatal hypothyroidism impairs the maturation of hypothalamic parvocellular CRF and AVP gene expression during this period (Dakine et al, 2000a) and delays the onset of mature ACTH and corticosterone responses to stress (Walker et al, 1989). On the other hand, perinatal T4 treatment induces an increase in CRH mRNA expression in the whole population of CRH synthesizing cells of the PVN (Dakine et al, 2000b), positively influences the development of the HPA diurnal rhythm (Lengvari et al, 1977), and accelerates a mature adrenocortical response to stress (Poland et al, 1979, Walker et al, 1989).…”

Section: Gestational States and Conditions That May Alter Or Intermentioning

confidence: 99%

Influence of maternal thyroid hormones during gestation on fetal brain development

et al. 2017

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Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention.

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“…After birth, there is a dramatic suppression of endogenous corticosterone (the rodent equivalent of cortisol) levels and a reduced ability to release this hormone in response to stressors [50,51]. This rodent “stress hyporesponsive period” begins before EGL NPCs become vulnerable to GC induced NPC apoptosis.…”

Section: The Role Of Glucocorticoids In Cerebellar Neurodevelopmentmentioning

confidence: 99%

Glucocorticoid Induced Cerebellar Toxicity in the Developing Neonate: Implications for Glucocorticoid Therapy during Bronchopulmonary Dysplasia

Noguchi

2014

Cells

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Prematurely born infants commonly suffer respiratory dysfunction due to the immature state of their lungs. As a result, clinicians often administer glucocorticoid (GC) therapy to accelerate lung maturation and reduce inflammation. Unfortunately, several studies have found GC therapy can also produce neuromotor/cognitive deficits and selectively stunt the cerebellum. However, despite its continued use, relatively little is known about how exposure to this hormone might produce neurodevelopmental deficits. In this review, we use rodent and human research to provide evidence that GC therapy may disrupt cerebellar development through the rapid induction of apoptosis in the cerebellar external granule layer (EGL). The EGL is a transient proliferative region responsible for the production of over 90% of the neurons in the cerebellum. During normal development, endogenous GC stimulation is thought to selectively signal the elimination of the EGL once production of new neurons is complete. As a result, GC therapy may precociously eliminate the EGL before it can produce enough neurons for normal cerebellar function. It is hoped that this review may provide information for future clinical research in addition to translational guidance for the safer use of GC therapy.

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Effects of experimental hypothyroidism on the development of the hypothalamo-pituitary-adrenal axis in the rat

Cited by 22 publications

References 0 publications

Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis

Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis

Influence of maternal thyroid hormones during gestation on fetal brain development

Glucocorticoid Induced Cerebellar Toxicity in the Developing Neonate: Implications for Glucocorticoid Therapy during Bronchopulmonary Dysplasia

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