The maintenance of hippocampal pyramidal neuron populations is dependent on the modulation of specific cell cycle regulators by thyroid hormones

Alva-Sánchez, Claudia; Sánchez-Huerta, Karla; Arroyo-Helguera, Omar; Anguiano, Brenda; Aceves, Carmen; Pacheco-Rosado, Jorge

doi:10.1016/j.brainres.2009.02.043

Cited by 32 publications

(17 citation statements)

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“…Moreover, the number and morphology of neuron in hippocampus are affected by neonatal and adult hypothyroidism [48,49]. As a marker of neuronal development, Nissl body diminishes when neuronal impairment.…”

Section: Discussionmentioning

confidence: 99%

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

et al. 2009

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BackgroundDevelopmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.MethodsThree developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42.ResultsThe iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42.ConclusionsDevelopmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.

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Section: Discussionmentioning

confidence: 99%

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

et al. 2009

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“…In previous studies we have observed that adult onset hypothyroidism causes significant changes in the morphology of the CA3 pyramidal cell population, involving neuronal atrophy [118]. Although it has been suggested that these effects of hypothyroidism could be caused by the induction of oxidative stress specifically in the hippocampus [88], the morphological alterations seem to be due primarily to the genomic actions of the THs on the signaling pathways controlling the cell cycle [119]. Finally, most studies in subclinical hypothyroid patients have found no clear detrimental effects attributable to subclinical thyroid disorders on physical, metabolic, and cognitive function in the elder population [120, 121].…”

Section: Thyroid Hormones and Aging: Clinical Correlationmentioning

confidence: 99%

The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration

Villanueva¹,

Alva-Sánchez²,

Pacheco-Rosado³

2013

Oxidative Medicine and Cellular Longevity

160

113

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Reactive oxygen species (ROS) are oxidizing agents amply implicated in tissue damage. ROS production is inevitably linked to ATP synthesis in most cells, and the rate of production is related to the rate of cell respiration. Multiple antioxidant mechanisms limit ROS dispersion and interaction with cell components, but, when the balance between ROS production and scavenging is lost, oxidative damage develops. Many traits of aging are related to oxidative damage by ROS, including neurodegenerative diseases. Thyroid hormones (THs) are a major factor controlling metabolic and respiratory rates in virtually all cell types in mammals. The general metabolic effect of THs is a relative acceleration of the basal metabolism that includes an increase of the rate of both catabolic and anabolic reactions. THs are related to oxidative stress not only by their stimulation of metabolism but also by their effects on antioxidant mechanisms. Thyroid dysfunction increases with age, so changes in THs levels in the elderly could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear. In this review, we analyze the participation of thyroid hormones on ROS production and oxidative stress, and the way the changes in thyroid status in aging are involved in neurodegenerative diseases.

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“…Clinical and experimental studies have reported a close relationship between low T3 levels and neurological problems such as memory deficits, anxiety and depression [18,19,20,21,22]. There is a wealth of information about the deleterious aspects associated with hypothyroidism and the underlying mechanisms [1,2,3,4,5,6,7,8,9]. However, the role played by oxidative stress in the etiology of the disease has been investigated only in the last decade.…”

Section: Introductionmentioning

confidence: 99%

“…The effects of thyroid hormones are mediated mainly via T3, which binds to nuclear receptors and controls the transcription of multiple cellular genes [1,2]. In effect, T3 can interact with nuclear receptors modulating specific cell cycle regulators and the pattern of expression of genes associated with the antioxidant defense systems [2,3,4,5,6,7]. Thyroid hormone signals are also involved in the crosstalk between a series of other intracellular signaling cascades, including the activation of mitogen-activated protein kinase pathways [2,8].…”

Section: Introductionmentioning

confidence: 99%

Diphenyl Diselenide Modulates Gene Expression of Antioxidant Enzymes in the Cerebral Cortex, Hippocampus and Striatum of Female Hypothyroid Rats

Dias¹,

Golombieski

Portella³

et al. 2014

Neuroendocrinology

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Introduction: Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. Aims: To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions. Methods: Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum. Results: Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes. Conclusion: The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state.

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The maintenance of hippocampal pyramidal neuron populations is dependent on the modulation of specific cell cycle regulators by thyroid hormones

Cited by 32 publications

References 50 publications

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration

Diphenyl Diselenide Modulates Gene Expression of Antioxidant Enzymes in the Cerebral Cortex, Hippocampus and Striatum of Female Hypothyroid Rats

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