The dynamics of dopamine receptor signaling efficacy were characterized in developing mice by measuring striatal c-Fos expression after dopaminergic agonist treatment at postnatal day 4 (P4) to P18. Control mice and mutant mice, in which dopamine production is inactivated in dopaminergic neurons by gene targeting, were treated with saline; a synthetic dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA) methyl ester; a direct dopamine D(1) receptor agonist, N-allyl-SKF 38393; or a dopamine reuptake inhibitor, cocaine. L-DOPA methyl ester treatment failed to induce striatal c-Fos immunoreactivity in control and mutant mice deficient in dopamine production at P4 and P6 compared with saline treatment.
View Article and Find Full Text PDFMultiple endocrine neoplasia type 2B (MEN2B) is an autosomal dominant syndrome characterized by the development of medullary thyroid carcinoma, pheochromocytomas, musculoskeletal anomalies and mucosal ganglioneuromas. MEN2B is caused by a specific mutation (Met918-->Thr) in the RET receptor tyrosine kinase. Different mutations of RET lead to other conditions including MEN2A, familial medullary thyroid carcinoma and intestinal aganglionosis (Hirschsprung disease).
View Article and Find Full Text PDFSympathetic neurons, enteric neurons and adrenal chromaffin cells all derive from the neural crest. During development these cells migrate, proliferate, survive and differentiate in a highly controlled fashion influenced by local signals encountered during their migration. Aberrations of these processes are responsible for a variety of developmental defects and malignancies.
View Article and Find Full Text PDFMetallothionein-III (MT-III), a brain-specific member of the metallothionein family of metal-binding proteins, is abundant in glutamatergic neurons that release zinc from their synaptic terminals, such as hippocampal pyramidal neurons and dentate granule cells. MT-III may be an important regulator of zinc in the nervous system, and its absence has been implicated in the development of Alzheimer's disease. However, the roles of MT-III in brain physiology and pathophysiology have not been elucidated.
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