Showing papers by "Valina L. Dawson published in 1991"
TL;DR: It is established that NO mediates the neurotoxicity of glutamate and Hemoglobin, which complexes NO, prevents neurotoxic effects of both N-methyl-D-aspartate and sodium nitroprusside.
Abstract: Nitric oxide (NO) mediates several biological actions, including relaxation of blood vessels, cytotoxicity of activated macrophages, and formation of cGMP by activation of glutamate receptors in cerebellar slices. Nitric oxide synthase (EC 1.14.23.-) immunoreactivity is colocalized with nicotinamide adenine di-nucleotide phosphate diaphorase in neurons that are uniquely resistant to toxic insults. We show that the nitric oxide synthase inhibitors, N omega-nitro-L-arginine (EC50 = 20 microM) and N omega-monomethyl-L-arginine (EC50 = 170 microM), prevent neurotoxicity elicited by N-methyl-D-aspartate and related excitatory amino acids. This effect is competitively reversed by L-arginine. Depletion of the culture medium of arginine by arginase or arginine-free growth medium completely attenuates N-methyl-D-aspartate toxicity. Sodium nitroprusside, which spontaneously releases NO, produces dose-dependent cell death that parallels cGMP formation. Hemoglobin, which complexes NO, prevents neurotoxic effects of both N-methyl-D-aspartate and sodium nitroprusside. These data establish that NO mediates the neurotoxicity of glutamate.
2,229 citations
TL;DR: The hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum is supported and long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat.
75 citations
TL;DR: The findings of downregulation of muscarinic receptors following long-term dopamine denervation and the subsequent normalization ofMuscarinic receptor density after fetal mesencephalic transplantation suggests that transplanted substantia nigra cells are able to restore inhibitory control on striatal cholinergic interneurons.
26 citations
TL;DR: The striatum (caudate nucleus and putamen) and its connections have been studied for some time due to their importance in the coordination and integration of normal motor function, as well as disorders of movement.
Abstract: The striatum (caudate nucleus and putamen; as opposed to the corpus striatum which includes the caudate nucleus and the lentiform nucleus comprised of the putamen and globus pallidus) and its connections have been studied for some time due to their importance in the coordination and integration of normal motor function, as well as disorders of movement (see Albin et al., 1989). These areas are thought to be the potential sites of action of many drugs which cause disturbances in movement (antipsychotics, amphetamines, etc.). Certain disorders such as Parkinson’s disease, Tourette’s syndrome, tardive dyskinesia, and Huntington’s disease appear to characteristically involve receptor alterations in the caudate and putamen (Waddington and O’Boyle, 1989; Seeman et al., 1987; Hess et al., 1987; Barnett, 1986). Several important neurotransmitter systems relevant to these disorders overlap in the caudate nucleus and putamen (indistinguishable as separate entities in the rat and collectively referred to as the caudate-putamen or CP) . These include the dopaminergic system, originating from the substantia nigra pars compacta (SNC) and the ventral tegmental region (Bjorklund and Lindvall, 1984), and the cholinergic system comprising, among others, a system of interneurons within the stroma of the nucleus itself (Graybiel and Ragsdale, 1983).
2 citations