Substantia pars compacta

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... 

Bums, R.S. Chieuh, C.C. Markey, S.P. Ebert, M.H. Jacobowitz, D.M. and Kopin, I.J. A primate model of parkinsonism Selective destraction of dopaminergic neurons in the pars compacta of the substantia nigra by n-methyl-4-phenyl-l,2,3,6-tetrahydropyridine.. Proc Natl Acad Sci USA 80 4546-4550, 1983. 

The neural structures involved in the promotion of the waking (W) state are located in the (1) brainstem [dorsal raphe nucleus (DRN), median raphe nucleus (MRN), locus coeruleus (LC), laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), and medial-pontine reticular formation (mPRF)] (2) hypothalamus [tuberomammillary nucleus (TMN) and lateral hypothalamus (LH)[ (3) basal forebrain (BFB) (medial septal area, nucleus basalis of Meynert) and (4) midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (Pace-Schott Hobson, 2002 Jones, 2003). The following neurotransmitters function to promote W (1) acetylcholine (ACh LDT/PPT, BFB) (2) noradrenaline (NA LC) (3) serotonin (5-HT DRN, MRN) (4) histamine (HA TMN) (5) glutamate (GLU mPRF, BFB, thalamus) (6) orexin (OX LH) and (7) dopamine (DA VTA, SNc) (Zoltoski et al, 1999 Monti, 2004). 

Consistent with receptor binding studies, k receptor mRNA is expressed in the claustrum and interpeduncular nucleus as well as the ventral tegmental area. High levels of k receptor mRNA levels are expressed in the substantia nigra pars compacta, suggestive that k receptors may be expressed in dopaminergic neurons with a presynaptic location. 

The two hallmark features in the substantia nigra pars compacta are loss of neurons and the presence of Lewy bodies. There is a positive correlation between the degree of nigrostriatal dopamine loss and severity of motor symptoms. PD is relatively asymptomatic until profound depletion (70% to 80%) of substantia nigra pars compacta neurons has occurred. 

Tsuneki H, Klink R, Ldna C, Kom H, Changeux JP (2000) Calcium mobilization ehcited by two types of nicotinic acetylcholine receptors in mouse substantia nigra pars compacta. Eur J Neurosci 12 2475-2485... 

In contrast to acetylcholine, dopamine has both excitatory (Dl) and inhibitory (D2 and D3) receptors. Dopaminergic neurons occur in two closely connected groups AlO—ventral tegmental area (VTA), and A9—substantia nigra, pars compacta (Fig. 3). While substantia nigra neurons project to the striatum, VTA... 

Functional circuitry between the cortex, basal ganglia, and thalamus. The major neurotransmitters are indicated. In Parkinson s disease, there is degeneration of the pars compacta of the substantia nigra, leading to overactivity in the indirect pathway (red) and increased glutamatergic activity by the subthalamic nucleus. 

Dopamine receptors are discussed in detail in Chapters 21 and 29. Dopamine receptors of the Di type are located in the pars compacta of the substantia nigra and presynaptically on striatal axons coming from cortical neurons and from dopaminergic cells in the substantia nigra. The D2 receptors are located postsynaptically on striatal neurons and... 

A high degree of coexistence of cholecystokinin-like and tyrosine hydroxylase-like immu-noreactivities has been observed in the substantia nigra pars compacta. Moreover, ventral mesencephalic cholecystokinin projections encompass the full range of the well-known dopaminergic, mesolimbic, mesostriatal, and mesocortical projections. Therefore, it should not be surprising that the intrastriatally injected cholecystokinin is able to stimulate dopamine-mediated transmission and to elevate the density of brain D2-dopamine receptors. 

A reduction in GSH has been detected in the substantia nigra pars compacta of patients with Parkinson s disease. Furthermore, a similar reduction in GSH has been found in substantia nigra pars compacta of cases with incidental Lewy body diseases, who are thought to have a preclinical form of Parkinson s disease. These findings suggest that a reduction in GSH, with the ensuing oxidative stress, may be a critical factor in the pathogenesis of Parkinson s disease. 

The pathological characteristic of Parkinson s disease is the selective degeneration of dopamine neurons in the pars compacta of the substantia nigra. The mechanism for the loss of neurons remains to be elucidated, and recently apoptosis has been proposed as a death process in Parkinson s disease. For example, the level of a product of the oxidative stress, 4-hydroxy-2-nonenal protein adduct, was found to increase in the nigral neurons of parkinsonian brains. Peroxynitrite (see Figure 13.6) has been proposed to be involved in the neuronal cell death in some neurodegenerative diseases, such as amyotrophic lateral sclerosis. 

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