ABSTRACT
The present study was undertaken to examine calmodulin-dependent effect of thyroid hormones (THs) on synaptosomal protein phosphorylation in mature rat brain. Effect of L-triiodothyronine (L-T3) on in vitro protein phosphorylation was measured in a hypotonic lysate of synaptosomes prepared from adult male rat cerebral cortex, incubated in presence and absence of calcium ion (Ca2+) and calmodulin. L-T3 significantly enhanced incorporation of 32P into synaptosomal proteins as compared to basal level of phosphorylation in the presence of Ca2+ and calmodulin. Under these conditions, increase in protein phosphorylation was 47, 74 and 52% for 10 nM, 100 nM and 1 M L-T3, respectively. Chelation of Ca2+ using ethylene glycol-bis (2‑aminoethylether)-N, N, N’, N’-tetraacetic acid (EGTA) inhibited the effects of Ca2+/calmodulin on TH-stimulated protein phosphorylation levels. This study suggests that a high proportion of L-T3-stimulated protein phosphorylation involves Ca2+/calmodulin-dependent pathways in adult rat cerebrocortical synaptosomes.
ABSTRACT
Thyroid hormones (TH) have important functions in maturation, differentiation and metabolism during developmental periods in almost all types of tissues including brain of vertebrate animals. In humans' thyroid malfunction in early developmental stages cause severe neuropsychological abnormalities due to defective gene expression via nuclear receptor activation. However, role of TH in adult mammalian brain is lacking and unclear mainly because it was considered for a long time as a TH unresponsive tissue. Although adult brain contains a substantial number of TH nuclear receptors, no functional properties could be attributed. Recent findings suggest that T3 is distributed, concentrated, metabolized and binds to specific membrane sites within adult brain. In mature humans TH also reversibly regulates various neuropsychological symptoms produced in mature condition. This review discusses development of recent concepts and literature on role of TH and its importance in neuronal function in adult mammalian brain.