Hypothyroidism following developmental iodine deficiency reduces hippocampal neurogranin, CaMK II and calmodulin and elevates calcineurin in lactational rats

Dong, Jing; Liu, Wanyang; Wang, Yi; Xi, Qi; Chen, Jie

doi:10.1016/j.ijdevneu.2010.07.230

Cited by 17 publications

(13 citation statements)

References 48 publications

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“…Developmental hypothyroidism or iodine-deficiency decreases the expression of neurogranin/RC3, a calmodulin-binding protein which is abundant in the hippocampal regions CA1, CA3 and DG throughout development and which plays a crucial role in regulating the post-synaptic availability of calmodulin and the subsequent activation of calmodulin-dependent pathways, including Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) (Dowling and Zoeller, 2000, Dong et al, 2010). Adult rats that were TH-deficient during development exhibit impairments in synaptic transmission and LTP in the DG and CA1 region, even after relatively moderate disruptions of thyroid function (Gilbert and Paczkowski, 2003, Gilbert and Sui, 2006, Opazo et al, 2008, Wang et al, 2013).…”

Section: Influence Of Ths On Brain and Cognitive Developmentmentioning

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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Section: Influence Of Ths On Brain and Cognitive Developmentmentioning

confidence: 99%

Influence of maternal thyroid hormones during gestation on fetal brain development

et al. 2017

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“…They regulate synaptic transmission (15), modulate the synthesis and turnover of neurotransmitters and modify the sensitivity of their receptors (42,51). They modulate signal transduction pathways in the CNS through Ca 2+ channels.…”

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confidence: 99%

The effect of omega-3 on cognition in hypothyroid adult male rats

Allah¹,

Gomaa²,

Sayed³

2014

Acta Physiologica Hungarica

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Thyroid hormones and omega-3 are essential for normal brain functions. Recent studies have suggested that omega-3 may protect against the risk of dementia. The aim of this study was to investigate the effect of hypothyroidism on spatial learning and memory in adult male rats, the underlying mechanisms and the possible therapeutic value of omega-3 supplementation. Thirty male rats were divided into three groups; control, hypothyroid and omega-3 treated. Hypothyroidism induced significant deficits in working and reference memories in radial arm maze, retention deficits in passive avoidance test and impaired intermediate and long-term memories in novel object recognition test. Serum total antioxidant capacity (TAC) and hippocampal serotonin and γ-aminobutyric acid (GABA) levels were decreased in the hypothyroid group as compared to the control group. Moreover, the hippocampus of hypothyroid rats showed marked structural changes as diffuse vacuolar degeneration and distortion of the pyramidal cells. Immunohistochemistry showed that the expression of Cav1.2 (the voltage dependent LTCC alpha 1c subunit) protein was increased in the hypothyroid group as compared to the control group. Omega-3 supplementation ameliorated memory deficits, increased TAC, decreased the structural changes and decreased the expression of Cav1.2 protein. In conclusion omega-3 could be useful as a neuroprotective agent against hypothyroidism-induced cognitive impairment.Keywords: hypothyroidism, cognition, omega-3, Cav1.2, GABA and serotonin Thyroid hormones play an important role in the development and the normal function of CNS by different mechanisms. They regulate synaptic transmission (15), modulate the synthesis and turnover of neurotransmitters and modify the sensitivity of their receptors (42, 51). They modulate signal transduction pathways in the CNS through Ca 2+ channels. L-type voltagesensitive Ca 2+ (Cav) channel (L-VSCC) mediates long lasting Ca 2+ currents (55) that play important roles in neurotransmitters release, second messenger cascades and gene regulation (28). L-VSCCs localize prominently on neuronal cell bodies and proximal dendrites (24). They consist of five subunits: α1, α2, β, γ and δ (40); α1 subunit is the ion-conducting pore and contains the binding sites for dihydropyridine (9). There are two different L-VSCC α1 subunits: α1C (Cav1.2) and α1D (Cav1.3) (47). Growing evidence has suggested that excessive Ca 2+ influx through L-VSCCs may be detrimental to memory (55). Moreover, L-VSCC currents were reported to be increased in the hippocampus of aged rats and rabbits and thus, had been implicated in aged-related memory deficits (50). Omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions including neural growth (18), neuroprotection and modulation of

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“…Thus far, NRGN was believed to be brain specific and abundant in forebrain neurons whose interactions with calmodulin are suggested to play an important role in the regulation of synaptic responses and plasticity [43, 44]. In brain, NRGN expression is dependent on thyroid hormones [45] and it is a direct target of thyroid hormone action [46–48]. There are numerous studies suggesting a link between thyroid and glomerular functions starting from embryogenesis [49] and involving chronic kidney disease as well as acute kidney injury [50], glomerular filtration rate [51] or resistant proteinuria [52].…”

Section: Discussionmentioning

confidence: 99%

A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity

et al. 2014

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BackgroundLarge scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis of gene expression (SAGE) was used for its unbiased approach to quantitative acquisition of transcripts.ResultsWe generated a HGMEC SAGE library consisting of 68,987 transcript tags. Then taking advantage of large public databases and advanced bioinformatics we compared the HGMEC SAGE library with a SAGE library of non-cultured ex vivo human glomeruli (44,334 tags) which contained endothelial cells. The 823 tags common to both which would have the potential to be expressed in vivo were subsequently checked against 822,008 tags from 16 non-glomerular endothelial SAGE libraries. This resulted in 268 transcript tags differentially overexpressed in HGMEC compared to non-glomerular endothelia. These tags were filtered using a set of criteria: never before shown in kidney or any type of endothelial cell, absent in all nephron regions except the glomerulus, more highly expressed than statistically expected in HGMEC. Neurogranin, a direct target of thyroid hormone action which had been thought to be brain specific and never shown in endothelial cells before, fulfilled these criteria. Its expression in glomerular endothelium in vitro and in vivo was then verified by real-time-PCR, sequencing and immunohistochemistry.ConclusionsOur results represent an extensive molecular characterization of HGMEC beyond a mere database, underline the endothelial heterogeneity, and propose neurogranin as a potential link in the kidney-thyroid axis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-725) contains supplementary material, which is available to authorized users.

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Hypothyroidism following developmental iodine deficiency reduces hippocampal neurogranin, CaMK II and calmodulin and elevates calcineurin in lactational rats

Cited by 17 publications

References 48 publications

Influence of maternal thyroid hormones during gestation on fetal brain development

Influence of maternal thyroid hormones during gestation on fetal brain development

The effect of omega-3 on cognition in hypothyroid adult male rats

A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity

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