دورية أكاديمية
Congenital hypothyroidism alters the oxidative status, enzyme activities and morphological parameters in the hippocampus of developing rats.
| العنوان: | Congenital hypothyroidism alters the oxidative status, enzyme activities and morphological parameters in the hippocampus of developing rats. |
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| المؤلفون: | Cattani D; Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil., Goulart PB, Cavalli VL, Winkelmann-Duarte E, Dos Santos AQ, Pierozan P, de Souza DF, Woehl VM, Fernandes MC, Silva FR, Gonçalves CA, Pessoa-Pureur R, Zamoner A |
| المصدر: | Molecular and cellular endocrinology [Mol Cell Endocrinol] 2013 Aug 15; Vol. 375 (1-2), pp. 14-26. Date of Electronic Publication: 2013 May 18. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: North Holland Publishing Country of Publication: Ireland NLM ID: 7500844 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8057 (Electronic) Linking ISSN: 03037207 NLM ISO Abbreviation: Mol Cell Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : North Holland Publishing Original Publication: Amsterdam, North-Holland. |
| مواضيع طبية MeSH: | Oxidative Stress*, Acetylcholinesterase/*metabolism , Congenital Hypothyroidism/*enzymology , Hippocampus/*enzymology, Animals ; Astrocytes/metabolism ; Cell Count ; Congenital Hypothyroidism/pathology ; Excitatory Amino Acid Transporter 1/metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; GPI-Linked Proteins/metabolism ; Glial Fibrillary Acidic Protein/metabolism ; Glutamic Acid/metabolism ; Hippocampus/growth & development ; Hippocampus/pathology ; Male ; Neurons/metabolism ; Rats ; Rats, Wistar ; S100 Calcium Binding Protein beta Subunit/metabolism ; Thyroid Hormones/blood |
| مستخلص: | Congenital hypothyroidism is associated with delay in cell migration and proliferation in brain tissue, impairment of synapse formation, misregulation of neurotransmitters, hypomyelination and mental retardation. However, the mechanisms underlying the neuropsychological deficits observed in congenital hypothyroidism are not completely understood. In the present study we proposed a mechanism by which hypothyroidism leads to hippocampal neurotoxicity. Congenital hypothyroidism induces c-Jun-N-terminal kinase (JNK) pathway activation leading to hyperphosphorylation of the glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits from hippocampal astrocytes and neurons, respectively. Moreover, hyperphosphorylation of the cytoskeletal proteins was not reversed by T3 and poorly reversed by T4. In addition, congenital hypothyroidism is associated with downregulation of astrocyte glutamate transporters (GLAST and GLT-1) leading to decreased glutamate uptake and subsequent influx of Ca(2+) through N-methyl-D-aspartate (NMDA) receptors. The Na(+)-coupled (14)C-α-methyl-amino-isobutyric acid ((14)C-MeAIB) accumulation into hippocampal cells also might cause an increase in the intracellular Ca(2+) concentration by opening voltage-dependent calcium channels (VDCC). The excessive influx of Ca(2+) through NMDA receptors and VDCCs might lead to an overload of Ca(2+) within the cells, which set off glutamate excitotoxicity and oxidative stress. The inhibited acetylcholinesterase (AChE) activity might also induce Ca(2+) influx. The inhibited glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyl transferase (GGT) activities, associated with altered glutamate and neutral amino acids uptake could somehow affect the GSH turnover, the antioxidant defense system, as well as the glutamate-glutamine cycle. Reduced levels of S100B and glial fibrillary acidic protein (GFAP) take part of the hypothyroid condition, suggesting a compromised astroglial/neuronal neurometabolic coupling which is probably related to the neurotoxic damage in hypothyroid brain. (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.) |
| المشرفين على المادة: | 0 (Excitatory Amino Acid Transporter 1) 0 (Excitatory Amino Acid Transporter 2) 0 (GPI-Linked Proteins) 0 (Glial Fibrillary Acidic Protein) 0 (S100 Calcium Binding Protein beta Subunit) 0 (S100b protein, rat) 0 (Slc1a2 protein, rat) 0 (Slc1a3 protein, rat) 0 (Thyroid Hormones) 3KX376GY7L (Glutamic Acid) EC 3.1.1.7 (Acetylcholinesterase) EC 3.1.1.7 (Ache protein, rat) |
| تواريخ الأحداث: | Date Created: 20130523 Date Completed: 20140204 Latest Revision: 20220330 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.mce.2013.05.001 |
| PMID: | 23693027 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-8057 |
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| DOI: | 10.1016/j.mce.2013.05.001 |