Immunocytochemical studies on the basal ganglia and substantia nigra in Parkinson's disease and Huntington's chorea. 1988

C M Waters, and R Peck, and M Rossor, and G P Reynolds, and S P Hunt
MRC Molecular Neurobiology Unit, University of Cambridge Medical School.

The basal ganglia and substantia nigra, taken from control human brain and from patients dying with a diagnosis of Parkinson's disease or Huntington's chorea, were analysed with histochemical and biochemical techniques. The pigmented neurons of the substantia nigra pars compacta possess tyrosine hydroxylase immunoreactivity and are disposed in three major layers, alpha, beta and gamma. This pattern became obscured in choreic brains by the severe shrinkage of the nigra, but total numbers of pigmented neurons were within the normal range. In contrast, pigmented neurons were lost from all layers of the substantia nigra in Parkinson's disease, although examination of cases with minimal cell loss suggested that an internal part of the lateral alpha sub-layer was most severely and consistently affected. A dopaminergic projection between this internal part of the alpha sub-layer and the putamen was suggested by the preferential loss of catecholamines from the putamen in Parkinson's disease. The distribution of the peptides, substance P, methionine-enkephalin and dynorphin 1-17 were mapped immunohistochemically within the substantia nigra. The different patterns of immunoreactive axons and terminals were found to be extensive, at least partially overlapping, and largely avoided the region of the pigmented perikarya of the alpha sub-layer and nucleus paranigralis. All peptides were depleted in choreic substantia nigra, reflecting the degeneration of the striatonigral pathway. However, concentrations of enkephalin-like immunoreactivity were increased within the interpeduncular nucleus. In Parkinson's disease there was a loss of enkephalin- and dynorphin-like immunoreactivity from the substantia nigra but a fall in substance P-like immunoreactivity was only detected by radioimmunoassay, not by immunocytochemistry. Peptide immunoreactivity was also reduced within choreic basal ganglia. However, no gross changes were found in peptide staining of the parkinsonian basal ganglia. In summary we have reported a number of changes in peptide-containing pathways in human degenerative disorders that may reflect the degeneration of neuronal pathways either as a primary event or secondary to initial lesion. We have also emphasized the sensitivity of the alpha sub-layer of nigral neurons to damage in Parkinson's disease. We suggest that the lower density of peptidergic fibres in the area of the perikarya may contribute to the susceptibility of these neurons to damage.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010300 Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D002395 Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from TYROSINE. Catecholamine,Sympathin,Sympathins
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D004745 Enkephalins One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. Enkephalin
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006816 Huntington Disease A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4) Huntington Chorea,Juvenile Huntington Disease,Akinetic-Rigid Variant of Huntington Disease,Chorea, Chronic Progressive Hereditary (Huntington),Chronic Progressive Hereditary Chorea (Huntington),Huntington Chronic Progressive Hereditary Chorea,Huntington Disease, Akinetic-Rigid Variant,Huntington Disease, Juvenile,Huntington Disease, Juvenile-Onset,Huntington Disease, Late Onset,Huntington's Chorea,Huntington's Disease,Juvenile-Onset Huntington Disease,Late-Onset Huntington Disease,Progressive Chorea, Chronic Hereditary (Huntington),Progressive Chorea, Hereditary, Chronic (Huntington),Akinetic Rigid Variant of Huntington Disease,Chorea, Huntington,Chorea, Huntington's,Huntington Disease, Akinetic Rigid Variant,Huntington Disease, Juvenile Onset,Huntington Disease, Late-Onset,Juvenile Onset Huntington Disease,Late Onset Huntington Disease

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