Dopamine substantia nigra

Neuromelanin, a dark colored pigment and product of the oxidative metabolism of dopamine, is found in the cytoplasm of dopaminergic neurons of the human substantia nigra pars compacta. Neuromelanin deposits increase with age, matching the age distribution of Parkinson s disease. In the absence of significant quantities of iron, neuromelanin can act as an antioxidant in... 

Kaxp channels under investigation resulted in selective rescue of substantia nigra dopaminergic neurons does not prove a deleterious, neurodegeneration-promoting role of Katp channels, but may simply mean that the dopamine neurons, lacking KATP channels, have developed other, undetected self-protection mechanisms. 

Adult dopamin-containing neurons in the substantia nigra rely on Cavl. 3 channels as pacemaker channels. It appears that the resulting enhanced Ca2+ load renders these channels more susceptible to neurotoxic effects and neurodegeneration as observed in Parkinson s disease. Preclinical evidence suggests that block of these with dihydropyridines causes a switch to a Cavl.3-independent pacemaker and protects these neurons from neurotoxicity. 

DAT (SLC6A3) Dopamine -5 CNS dopaminergic neurons (emanate from substantia nigra, other mid brain nuclei, hypothalamus) ... 

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

French ED, Dillon K, Wu X Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 8 649—632, 1997 Fujinaga M, Maze M Neurobiology of nitrous oxide-induced antinociceptive effects. Mol Neurobiol 25 167-189, 2002... 

Of course, while the identification of these distinct systems may be useful there are many neural pathways that would not fit easily into one of them. Thus some inhibitory pathways, such as that from the caudate nucleus to substantia nigra, utilising GABA, are not intrinsic neurons. The dopamine pathway from the substantia nigra to striatum may start from a small nucleus but unlike other monoamine pathways it shows little ramification beyond its influence on the striatum. The object of the above classification is not to fit all neural pathways and mechanisms into a restricted number of functional categories but again to demonstrate that there are different forms of neurotransmission. 

Figure 7.1 Dopamine neuronal pathways. AMYG, amygdala CN, caudate nucleus MFB, medial forebrain bundle NcA, nucleus accumbers OT, olfactory tubercle PUT, putamen SN, substantia nigra. For full details see text and Moore and Bloom (1978) and Lindvall and Bjorkland (1978)...

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

Cheramy, A, Leviel, V and Glowinski, J (1981) Dendritic release of dopamine in the substantia nigra. Nature 289 537-542. 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

Figure 15.11 Possible scheme for the formation of free radicals from the metabolism of dopamine. Normally hydrogen peroxide formed from the deamination of DA is detoxified to H2O along with the production of oxidised glutathione (GSSG) from its reduced form (GSH), by glutathione peroxidase. This reaction is restricted in the brain, however, because of low levels of the peroxidase. By contrast the formation of the reactive OH-radical (toxification) is enhanced in the substantia nigra because of its high levels of active iron and the low concentration of transferin to bind it. This potential toxic process could be enhanced by extra DA formed from levodopa in the therapy of PD (see Olanow 1993 and Olanow et al. 1998)...

Double, K.L. et al., Structural characteristics of human substantia nigra neuromelanin and synthetic dopamine melanins, J. Neurochem., 75, 2583, 2000. 

The inhibition of firing of catecholamine neurons resulting from amphetamine administration is likely due to activation of somatodendritic autoreceptors. This causes a hyperpolarization of the somatodendritic membrane of both locus coeruleus noradrenergic and substantia nigra dopamine neurons, probably as a consequence of an increase in potassium conductance (Lacey et al. 1987 Williams et al. 1985). 

Lacey, M.G. Mercuri, N.B. and North, R.A. Dopamine acts on D2 receptors to increase potassium conductance in neurons of the rat substantia nigra zona compacta. J Physiol 392 397-416, 1987. 

Matthews, R.T., and German, D.C. Evidenee for a funetional role of dopamine type 1 (D-1) receptors in the substantia nigra of rats. 

Olds, M.E. Amphetamine-induced increase in motor aetivity is correlated with higher firing rates of non-dopamine neurons in substantia nigra and ventral tegmental areas. Neurosci 24 477-490, 1988. 

Reubi, J.-C. Iversen, L.L. and Jessell, T.M. Dopamine selectively increases H-GABA release from slices of rat substantia nigra in vitro. Nature 268 652-654, 1977. 

Waszezak, B.L., and Walters, J.R. Dopamine modulation of the effects of y-aminobutyric acid on substantia nigra pars reticulata neurons. Science 220 218-221, 1983. 

Benkirane, S. Arbilla, S. and hanger, S.Z. A functional response to D1 dopamine receptor stimulation in the central nervous system Inhibition of the release of [ H]-serotonin from the rat substantia nigra. Naunyn-Schmiedebergs Arch Pharmacol 335 502-507, 1987. 

Fessler, R.G. Sturgeon, R. and Meltzer, H.Y. Phencyclidine-induced iosilateral rotation in rats with unilateral 6-hydroxy-dopamine-induced lesions of the substantia nigra. I ife Sci 24 1281-1288, 1979. 

Parkinsons disease (PD) is a slow, progressive, neurodegenera-tive disease of the extrapyramidal motor system. Dopamine neurons in the substantia nigra are primarily affected, and degeneration of these neurons causes a disruption in the ability... 

The extrapyramidal motor system controls muscle movement through a system of pathways and nerve tracts that connect the cerebral cortex, basal ganglia, thalamus, cerebellum, reticular formation, and spinal neurons. Patients with PD lose dopamine neurons in the substantia nigra, which is located in the midbrain within the brain stem. The substantia... 

Substantia nigra The area in the brain stem that makes dopamine. 

---