Thyroid hormone regulates TAG‐1 expression in the developing rat brain

Abstract

TAG-1 is a member of the immunoglobulin superfamily of cell adhesion molecules thought to play important roles in neuronal differentiation and the establishment of connectivity during brain development. Because these are processes also affected by hypothyroidism, we studied the effects of thyroid hormone deprivation and administration on TAG-1 expression in the developing rat brain. By in situ hybridization, immunohistochemistry and Western blotting we found that TAG-1 RNA and protein levels are upregulated in the hypothyroid brain. From embryonic day 20 to postnatal day (P) 15, elevated TAG-1 RNA was found in several areas including the cerebral cortex, hippocampus and olfactory bulb. In agreement with this, TAG-1 protein was overexpressed in the major fibre tracts arising from these structures, including the corpus callosum, anterior and hippocampal commissures and lateral olfactory tract. A similar overexpression of TAG-1 by hypothyroidism was detected in the cerebellum, but starting only at P15. In all cases, elevation of TAG-1 RNA and protein expression could be reversed by thyroid hormone treatment. These results show that the deregulation of TAG-1 might contribute to the alterations caused by the lack of thyroid hormone during brain development.

Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly

“…Several candidate neuroregulatory molecules such as NT4, 59 Tbr-1, 60 BDNF 61 and thyroid hormone 36,62 have recently been shown to modulate Reelin levels directly, providing further potential treatment options for the aforementioned neuropsychiatric disorders.…”

“…27 Several experimental paradigms and various animal models also cause decreases in Reelin production with cortical and behavioral abnormalities ( Table 2); these include heterozygous reeler mouse mutant, 28 after x-irradiation, 29 prenatal human influenza viral infection, [30][31][32][33] domoic acid lesion of Cajal-Rezius cells, 34 after thromboxane A2 treatment 35 and in experimental hypothyroidism. 36 Of interest, are several brain structural and functional deficits which have been observed in heterozygous reeler mutation 28 and in progeny of mouse mothers exposed to human influenza viral infections, [30][31][32][33] that are similar to those found in adult patients with schizophrenia, such as 50% reduction in Reelin protein, 1-3 abnormal prepulse inhibition 28 (Shi, Fatemi, Patterson, unpublished data) and alterations in density of nNOS containing cells in the neocortex. 28,33 Reelin is a glycoprotein with a relative molecular mass of 388 kDa, which was discovered in 1995.…”

Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals

“…Contactin-2/ TAG-1 is expressed during adulthood in the juxtaparanodal region of myelinated fibers by oligodendrocytes, Schwann cells, and axons, where it interacts with itself (21,22). Contactin-2/TAG-1 is also expressed by neurons in the gray matter of the hippocampus (23) and the spinal cord (24). This distribution led us to speculate that autoimmune responses to contactin-2 might be involved in the development of gray matter lesions in MS.…”

Novel two-dimensional morphometric maps and quantitative analysis reveal marked growth and structural recovery of the rat hippocampal regions from early hypothyroid retardation

“…A few previous studies investigated the deleterious effects of thyroid hormone deficiency on the developing hippocampus (HC) (Gould, et al 1991,Lauder & Mugnaini, 1977,1980Rabie et al, 1979;Rami & Rabie, 1988;Rami et al, 1986a,b). Recently several molecular and functional studies have also appeared (Alvarez- Dolado et al, 2001;Alzoubi et al, 2005;Ambrogini et al, 2005;Desouza et al, 2005;Dong et al, 2005;Gerges & Alkadhi, 2004,Gilbert, 2004Gilbert & Paczkowski, 2003;Martinez et al, 2001;Matos, et al 2002;Meaney et al, 2000;Roskoden et al, 1999;Sui & Gilbert, 2003;Uchida et al, 2005;Vaidya et al, 2001;Vara et al, 2002Vara et al, ,2003.…”