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Developmental hypothyroxinaemia and hypothyroidism limit dendritic growth of cerebellar P urkinje cells in rat offspring: involvement of microtubule‐associated protein 2 ( MAP 2) and stathmin
Author(s) -
Wang Yuan,
Wang Yi,
Dong Jing,
Wei Wei,
Song Binbin,
Min Hui,
Teng Weiping,
Chen Jie
Publication year - 2014
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12074
Subject(s) - stathmin , phosphorylation , endocrinology , medicine , microtubule , cerebellum , offspring , biology , dendritic spine , microbiology and biotechnology , genetics , hippocampal formation , pregnancy
Aims Iodine is essential for the synthesis of thyroid hormone. Iodine deficiency ( ID )‐induced hypothyroxinaemia and hypothyroidism during developmental period contribute to impairments of function in the brain, such as psychomotor and motor alterations. However, the mechanisms are still unclear. Therefore, the present research is to study the effects of developmental hypothyroxinaemia caused by mild ID and developmental hypothyroidism caused by severe ID or methimazole ( MMZ ) on dendritic growth in filial cerebellar P urkinje cells ( PCs ) and the underlying mechanisms. Methods A maternal hypothyroxinaemia model was established in W istar rats using a mild ID diet, and two maternal hypothyroidism models were developed with either severe ID diet or MMZ water. We examined the total dendritic length using immunofluorescence, and W estern blot analysis was conducted to investigate the activity of microtubule‐associated protein 2 ( MAP 2), stathmin and calcium/calmodulin‐dependent protein kinase II ( CaMKII ). Results Hypothyroxinaemia and hypothyroidism reduced the total dendritic length of cerebellar PCs , decreased MAP 2 and its phosphorylation, increased stathmin but reduced its phosphorylation and down‐regulated the activity of CaMKII and its phosphorylation in cerebellar PCs on postnatal day ( PN ) 7, PN 14 and PN 21. Conclusion Developmental hypothyroxinaemia induced by mild ID and hypothyroidism induced by severe ID or MMZ limit PCs dendritic growth, which may involve in the disturbance of MAP 2 and stathmin in a CaMKII ‐dependent manner. It suggests a potential mechanism of motor coordination impairments caused by developmental hypothyroxinaemia and hypothyroidism.