Reduced striatal [3H]inositol 1,4,5-trisphosphate binding in Huntington's disease. 1991

J J Warsh, and J M Politsky, and P P Li, and S J Kish, and O Hornykiewicz
Department of Psychiatry, University of Toronto, Ontario, Canada.

Specific [3H]inositol 1,4,5-trisphosphate [( 3H]InsP3) binding was studied in regions of postmortem brain from 15 patients with Huntington's disease (HD) and 13 nonneurological controls. Single-point binding analyses, using 5.0 nM InsP3, showed statistically significant reductions in specific [3H]InsP3 binding in the caudate (-71%) and putamen (-75%) of HD patients compared with controls. Frontal and occipital cortical [3H]InsP3 binding was not significantly different between HD and controls, a finding suggesting that the reduced [3H]InsP3 binding parallels the brain regional specificity of the neuropathological changes in HD. Scatchard analyses of data from [3H]InsP3 competition binding assays performed on caudate nucleus revealed that the reductions found using single-point binding assays were due to a decrease in both binding density (-57%) and affinity (-50%) in HD brain compared with controls. The concomitant changes in InsP3 receptor density and affinity in HD brain suggest that these alterations may be produced by processes in addition to cell loss. These results suggest the possibility that disturbances in InsP3 receptor function, possibly resulting in altered intracellular calcium flux and homeostasis, occur in HD and may participate in the pathogenesis of this neurodegenerative disorder.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011180 Postmortem Changes Physiological changes that occur in bodies after death. Adipocere,Algor Mortis,Cruor,Livor Mortis,Change, Postmortem,Changes, Postmortem,Postmortem Change
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D005260 Female Females
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol
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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