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Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require(More)
The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development. Here we demonstrate that it binds Patched (vPtc), which has been identified as a tumour-suppressor protein in basal cell carcinoma, with high affinity. We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein(More)
The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both(More)
Sonic hedgehog (Shh) is a putative morphogen secreted by the floor plate and notochord, which specifies the fate of multiple cell types in the ventral aspect of the vertebrate nervous system. Since in Drosophila the actions of Hh have been shown to be transduced by Cubitus interruptus (Ci), a zinc finger transcription factor, we examined whether a(More)
Sonic Hedgehog (Shh) is a secreted protein that controls cell fate and mitogenesis in the developing nervous system. Here we show that a constitutively active form of Smoothened (Smo-M2) mimics concentration-dependent actions of Shh in the developing neural tube, including activation of ventral marker genes (HNF3beta, patched, Nkx2.2, netrin-1), suppression(More)
The effects of subcutaneous injection of 3,4-methylenedioxymethamphetamine (MDMA), a psychoactive amphetamine congener, on mouse central monoaminergic systems were assessed and compared to effects in rats. Whereas neostriatal concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in mouse were transiently decreased after a single moderately(More)
Similar to other amphetamine analogs 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), a currently popular illicit drug, has been characterized recently as a serotonergic neurotoxin due to its ability to cause long-lasting deficits in markers of central serotonergic function in animals. Because the serotonergic toxicity associated with the MDMA analog(More)
Tryptophan hydroxylase (TPH) from central serotonergic neurons in the dorsal raphe nucleus (DRN) and that from the endocrine pineal gland (PG) have been shown to exhibit difference biochemical characteristics. We further report here that the isoelectric point determined by chromatofocusing differs between TPH from the rat brainstem and PG. In addition, the(More)
The activity of tryptophan hydroxylase (EC from rat brain was significantly decreased 1 h following a single systemic injection of 3,4-methylenedioxymethamphetamine (MDMA) when assessed ex vivo by radioenzymatic assay or in vivo by the quantitation of 5-hydroxytryptophan accumulation following central L-aromatic amino acid decarboxylase(More)
Tyrosine hydroxylase (TH) mRNA, immunoreactivity, and activity were examined as a reflection of dopamine expression in juxtaglomerular neurons intrinsic to the olfactory bulbs of young (6-month-old), middle aged (18-month-old), and aged (25- to 29-month-old) rats and mice. TH expression was maintained at levels observed in young animals in the olfactory(More)