Substantia nigra

Catalase-positive microperoxisomes are relatively abundant in catecholaminic areas of the rat brain, as McKenna et al. (1976) showed in the substantia nigra, the locus coeruleus and in nucleus Aj of the medulla. Approximately half of the neurones in the zona compacta substantiae nigrae (nucleus A9) contain moderate numbers of catalase-positive bodies, while the remaining neurones contain few or none. 

1 - Methyl - 4 - phenyl -1,2,3,6 - tetrahydropyridine (MPTP) is a frequently used animal model for Parkinson s disease. When injected into animals, MPTP is taken up by the cells in the substantia nigra where monoamino oxidase B (EC 1.4.3.4) converts it to l-methyl-4-phenylpyridinium ion (MPP ). This ion induces free radicals and duplicates many of the signs of Parkinson s disease in animals. In mice melatonin attenuated the resulting damage in the central nervous system (Acuna-Castroviejo et al. 1997). MPTP-induced neural lipid peroxidation was reduced to control levels when melatonin was co-administered with the herbicide. Neuronal loss and MPTP-induced reduction of tyrosine hydroxylase (EC 1.14.16.2) activity in neurones of the striatum were attenuated by melatonin. 

Two main subdivisions have been recognized in the SN since the first detailed studies of this structure (Mingazzini, 1888 Sano, 1910 Cajal, 1911). In particular, Mingazzini (1888), who impregnated human midbrain tissue with the Golgi technique, was so impressed by the appearance of the different portions of the SN that he considered the organization of this structure similar to the layered organization of the cerebral cortex and described the SN neurons as pyramidal cells. 

The two main subdivisions of the SN are the SNc, characterized by densely packed neurons (as the Latin adjective compacta indicates), and the pars reticulata (SNr) characterized by sparser cells, enmeshed in fibers (which are the termination of the striatonigral pathway) as in a net (as the Latin adjective reticulata indicates) (Figs. 4A,B,E,F 5 and 6). A third portion, the pars lateralis (SN1), is formed by a small elliptical mass of neurons in the rostral and the dorsolateral portion of the SN (Figs. 4A,E,F and 6). The SN1 has many features in common with the other two subdivisions, 

peripeduncular nucleus PR, prerubral field Reth, retroethmoid nucleus RMC, red nucleus, magnocellular RPC, red nucleus, parvocellular scp, superior cerebellar peduncle SNC, substantia nigra, compact part SNL, substantia nigra, lateral part SNR, substantia nigra, reticular part SPFPC, subparafascicular thalamic nucleus, parvocellular part SuML, supramammillary nucleus, lateral part VTA, ventral tegmental area VTM, ventral tuberomammillary nucleus ZID, zona incerta, dorsal part ZIV, zona incerta, ventral part 3, oculomotor nucleus 3n, oculomotor nerve or its root. Reproduced with permission from Paxinos and Watson (1998) and Paxinos et al. (1999). 

According to the study of Poirier et al. (1983), in the rat the SN of either side has about 22,400 neurons, and 44% belong to the SNc, whereas in the cat, the SN has about 38,400 neurons (58% of which belong to the SNc), and the proportion of SNc cells increases in primates (about 73,500 neurons in the SN, 85% of which are located in the SNc). With some unavoidable variation, these numbers are roughly in agreement with the quantitative evaluations of the DA-containing cells identified with TH immunoreactivity (see Section 2.3). 

On the other hand, neurons in the most ventral part of the SNr were seen to give off dendrites oriented parallel to the cerebral peduncle. 

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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. 

While advances in the symptomatic drug therapy (summarized below) have certainly improved the lives of many Parkinson patients, the goal of current research is to develop treatments that can prevent, retard or reverse the death of dopaminergic neurons in the substantia nigra pats compacta (and of other neurons involved in the pathogenesis of Parkinson s disease not mentioned in this essay). 

Substantia nigra pars reticulata is the area with highest neuronal activity and metabolic rate in the brain. This region also shows highest expression rates of SUR1/ Kir6.2 channels. These KATP channels are present... 

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. 

Localization CNS Hippocampus (CA1, CA3, DG), septum, amygdala, raphe nuclei CNS Striatum, hippocampus (CA1), substantia nigra, globus pallidus, superior colliculi, spinal cord, raphe nuclei CNS like 5-HT1B but at lower densities. CNS Caudate putamen, parietal cortex, fronto-parietal motor cortex, olfactory tubercle, amygdala CNS Cortex, Thalamus, olfactory bulb (rat), claustrum (g-pig), hippocampus (CA3), spinal cord. 

Localization CNS Cortex, hippocampus, striatum, olfactory bulb, spinal cord CA/S not present in adult. CNS Choroid plexus, medulla, pons, striatum, hippocampus (CA1, CA3), hypothalamus, spinal cord CNS Striatum, hippocampus (CA1), substantia nigra, globus pal-lidus. CNS Striatum, brainstem, thalamus, hippocampus, olfactory bulb, substantia nigra... 

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... 

Fig. 8.1 (continued) nucleus, (k, 1) Hi hippocampus, (m, n) So supraoptic nucleus, (o, p) Arc hypothalamic arcuate nucleus, (q, r) PH posterior hypothalamic area, (s, t) SN Substantia nigra. AU sections were observed with an Olympus fluorescent microscope (BX 61). Scale bars = 50 mm. (Unpubhshed data)... 

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. 

In addition to its vital role in the metabolism of ACh, acetylcholinesterase has been shown somewhat surprisingly to be released in the substantia nigra, along with DA,... 

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