These authors contributed equally to this work.
Developmental hypothyroxinaemia and hypothyroidism limit dendritic growth of cerebellar Purkinje cells in rat offspring: involvement of microtubule-associated protein 2 (MAP2) and stathmin
Article first published online: 22 APR 2014
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 40, Issue 4, pages 398–415, June 2014
How to Cite
Wang, Y., Wang, Y., Dong, J., Wei, W., Song, B., Min, H., Teng, W. and Chen, J. (2014), Developmental hypothyroxinaemia and hypothyroidism limit dendritic growth of cerebellar Purkinje cells in rat offspring: involvement of microtubule-associated protein 2 (MAP2) and stathmin. Neuropathology and Applied Neurobiology, 40: 398–415. doi: 10.1111/nan.12074
- Issue published online: 22 APR 2014
- Article first published online: 22 APR 2014
- Accepted manuscript online: 11 JUL 2013 01:12AM EST
- Manuscript Accepted: 4 JUL 2013
- Manuscript Received: 11 APR 2013
- National Natural Science Foundation of China. Grant Numbers: 30800896, 81102126
- Program for Liaoning Excellent Talents in University. Grant Number: LJQ2012070
- iodine deficiency;
- Purkinje cells
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 Purkinje cells (PCs) and the underlying mechanisms.
A maternal hypothyroxinaemia model was established in Wistar 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 Western blot analysis was conducted to investigate the activity of microtubule-associated protein 2 (MAP2), stathmin and calcium/calmodulin-dependent protein kinase II (CaMKII).
Hypothyroxinaemia and hypothyroidism reduced the total dendritic length of cerebellar PCs, decreased MAP2 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, PN14 and PN21.
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 MAP2 and stathmin in a CaMKII-dependent manner. It suggests a potential mechanism of motor coordination impairments caused by developmental hypothyroxinaemia and hypothyroidism.