Reduction of thyroid hormone receptor c-ERB Aα mRNA levels in the hippocampus of Alzheimer as compared to huntington brain

Sutherland, May Kung; Wong, Lee Jun; Somerville, Martin J.; Handley, Patricia; Yoong, Larry K.K.; Bergeron, Catherine; McLachlan, Donald R.

doi:10.1016/0197-4580(92)90043-w

Cited by 28 publications

(15 citation statements)

References 45 publications

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“…The present data demonstrate, moreover, that this decreased expression of TR in aged animals resulted, at least in part, from a transcriptional event. This finding could be related to results obtained in Alzheimer cases (disease regarded as a pathological form of aging) showing a decreased level of TR mRNA, particularly of the sub‐type TRα, in Alzheimer hippocampus [25]. Data on the influence of T 3 in the regulation of expression of TR genes are few but it has been shown that TR genes have a positive responsiveness to T 3 administration [26], and that thyroid hormone up‐regulates TRβ gene expression in rat cerebral hemisphere astrocyte cultures [27].…”

Section: Discussionsupporting

confidence: 56%

Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids

et al. 1997

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Aging is accompanied by troubles resulting from changes in hormonal and nutritional status. Therefore, the abundance of mRNA coding for triiodothyronine (TR) and retinoic acid (RA) nuclear receptors was studied in the brain of young, adult and aged (2.5, 6 and 24 months, respectively) rats. In the brain of aged rats, there was a lower abundance of TR and RAR mRNA and a lower activity of tissue transglutaminase (tTG), an enzyme the gene of which is a target for retinoids. Administration of RA in these rats restored TR and RAR mRNA and the activity of tTG in the brain. The importance of these observations to the function of the aged brain is discussed.

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Section: Discussionsupporting

confidence: 56%

Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids

et al. 1997

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“…In addition to the repressive effect of the thyroid hormone on APP mRNA levels and APP promoter activity, we have previously demonstrated that thyroid hormones specifically alter the pattern of intracellular and secreted APP isoforms (13). Our results together with the reduction of thyroid hormone receptor levels observed in Alzheimer hippocampal cells (44) and the effects exerted by estradiol or retinoic acid on APP expression and metabolism (9, 45) strongly suggest that members of the nuclear superfamily of receptors and their ligands might play an important role in Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 78%

Thyroid Hormone Negatively Regulates the Transcriptional Activity of the β-Amyloid Precursor Protein Gene

Belandia

Latasa

Villa

et al. 1998

Journal of Biological Chemistry

101

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The expression of the ␤-amyloid precursor protein (APP), which plays a key role in the development of Alzheimer's disease, is regulated by a variety of cellular mediators in a cell-dependent manner. In the present study, we present evidence that thyroid hormones negatively regulate the expression of the APP gene in neuroblastoma cells. Transient transfection studies using plasmids that contain progressive deletions of the 5 region of the gene demonstrate that triiodothyronine (T3), the more active form of the thyroid hormones, represses APP promoter activity by a mechanism that requires binding of the nuclear T3 receptor (TR) to a specific sequence located in the first exon. The unliganded receptor increases promoter activity, and T3 reverses that activity to basal levels. The repressive effect of T3 does not exhibit TR isoform specificity, and it is equally mediated by TR␣ and TR␤. Gel mobility shift assays using in vitro synthesized nuclear receptors and nuclear extracts led to the identification of a negative thyroid hormone response element, at nucleotide position ؉80/ ؉96, that preferentially binds heterodimers of TR with the retinoid X receptor. Insertion of sequences containing this element confers negative regulation by T3 to a heterologous TK promoter, thus indicating the functionality of the element.

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“…These results are interesting in view of the neurological symptoms displayed by hypothyroid patients, which resemble in part those manifested by Alzheimer patients, and in view of the reduction in thyroid hormone receptor a-c-erbA mRNA levels in the hippocampus of Alzheimer brains (Kung Sutherland et al, 1992). eu-, hypo-and hyperthyroid rats after saline or kainic acid administration.…”

Section: Discussionmentioning

confidence: 91%

Neurotrophins and their Receptors in the Adult Hypo‐ and Hyperthyroid Rat after Kainic Acid Injection: an In Situ Hybridization Study

Calzà

Giardino

Ceccatelli³

et al. 1996

Eur J of Neuroscience

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Thyroid hormone plays a key role in trophic events during development of the central nervous system. In spite of neurological and psychiatric symptoms associated with adult hypothyroidism, the role of thyroid hormone in mature brain function is less clear. In this paper we investigated the effect of thyroid status on kainic acid-induced up-regulation of mRNAs for members of the nerve growth factor family and related receptors in adult male rats by means of in situ hybridization. We found that in hypothyroid rats there is a dramatic attenuation of the kainic acid-induced up-regulation of mRNA levels for nerve growth factor, brain-derived neurotrophic factor and tyrosine kinase trkB in euthyroid rats. A trend to reduced c-fos mRNA up-regulation, which did not reach significance, was also found, whereas the increase in c-jun mRNA after kainic acid was similar in eu-, hypo- and hyperthyroid rats. These data indicate a severe impairment of the regulation of neurotrophin synthesis after excitotoxin administration in the hippocampus during adult hypothyroidism. Possible roles of thyroid hormone in molecular, biochemical and metabolic mechanisms of this defect are discussed.

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Reduction of thyroid hormone receptor c-ERB Aα mRNA levels in the hippocampus of Alzheimer as compared to huntington brain

Cited by 28 publications

References 45 publications

Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids

Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids

Thyroid Hormone Negatively Regulates the Transcriptional Activity of the β-Amyloid Precursor Protein Gene

Neurotrophins and their Receptors in the Adult Hypo‐ and Hyperthyroid Rat after Kainic Acid Injection: an In Situ Hybridization Study

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