Developmental Iodine Deficiency and Hypothyroidism Impair Neural Development, Upregulate Caveolin-1, and Downregulate Synaptotagmin-1 in the Rat Cerebellum

Abstract

Adequate thyroid hormone is critical for cerebellar development. Developmental hypothyroidism induced by iodine deficiency during gestation and postnatal period results in permanent impairments of cerebellar development with an unclear mechanism. In the present study, we implicate cerebellar caveolin-1 and synaptotagmin-1, the two important molecules involved in neuronal development, in developmental iodine deficiency, and in developmental hypothyroidism. Two developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 or 15 ppm)-added drinking water from gestational day 6 till postnatal day (PN) 28. Nissl staining and the levels of caveolin-1 and synaptotagmin-1 in cerebella were assessed on PN28 and PN42. The results show that the numbers of Purkinje cells were reduced in the iodine-deficient and PTU-treated rats. The upregulation of caveolin-1 and the downregulation of synaptotagmin-1 were observed in both iodine-deficient and PTU-treated rats. These findings may implicate decreases in the number of Purkinje cells and the alterations in the levels of caveolin-1 and synaptotagmin-1 in the impairments of cerebellar development induced by developmental iodine deficiency and hypothyroidism.

Manganese-mediated acceleration of age-related hearing loss in mice

“…Nissl staining was performed with paraffin sections. Stained cells with round and palely stained nuclei were considered to be surviving cells, whereas shrunken cells with pyknotic nuclei were considered to be nonsurviving cells as described previously42. Immunohistochemistries with polyclonal antibodies against c-Ret protein (1:100; Immuno Biological Laboratories), phosphorylated c-Ret Y1062 (1:100; Abcam) and phosphorylated NF-κB p50 (1:50; Santa Cruz) were performed for frozen sections with Can Get Signal immunostaining solution (TOYOBO).…”

Resveratrol improved the spatial learning and memory in subclinical hypothyroidism rat induced by hemi-thyroid electrocauterization

“…It has been demonstrated that thyroid dysfunction affected synaptic proteins in adult rats [26]. Thyroid hormone deficiency resulted in the down-regulation of syt-1 expression in rat hippocampus [25,27] and cerebellum [28], and the impairment in hippocampal-dependent tasks of learning and memory [29]. These findings emphasized a close relationship between thyroid dysfunction and syt-1.…”

The Effect of Mackerel Meat on the Number of Purkinje Cell in the Cerebellum of Congenital Hypothyroid Rat (Rattus norvegicus)

“…Brain damage is mainly found in the prefrontal, hippocampus and cerebellar cortex 5 . This is caused by cell propagation disorders (proliferation), cell migration, cell differentiation, and decreases in synapses formation, myelin formation, neuron growth, neurotransmitter formation, and increased cell death and astrocytic proliferation, and consequently the connectivity between neurons perfect 6 . Connectivity between parts of the brain is an essential requirement for cognitive function 6 .…”

“…This is caused by cell propagation disorders (proliferation), cell migration, cell differentiation, and decreases in synapses formation, myelin formation, neuron growth, neurotransmitter formation, and increased cell death and astrocytic proliferation, and consequently the connectivity between neurons perfect 6 . Connectivity between parts of the brain is an essential requirement for cognitive function 6 . In addition, hypothyroidism can also cause mental retardation, and decreases speech and hearing ability and motor impairment.…”