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Chemical pathology of Huntington's disease
Insights
Huntington's disease (HD) involves brain neuron degeneration, particularly in the basal ganglia. Research found altered neurotransmitter levels, including decreased gamma-aminobutyric acid and increased dopamine, impacting brain function.
Area of Science:
- Neuroscience
- Neurobiology
- Neurology
Background:
- Huntington's disease (HD) is a dominantly inherited neurological disorder.
- HD typically manifests in middle age with characteristic involuntary movements.
- Neuronal degeneration occurs throughout the brain, with pronounced effects in the basal ganglia.
Purpose of the Study:
- To investigate neurochemical alterations in postmortem brains of Huntington's disease patients.
- To compare neurotransmitter and enzyme activity in HD brains versus controls.
Main Methods:
- Neurochemical analysis of postmortem brain tissue from HD patients and controls.
- Measurement of neurotransmitter concentrations and enzyme activities.
Main Results:
- Decreased concentrations of gamma-aminobutyric acid (GABA) in the basal ganglia.
- Increased concentrations of dopamine and serotonin in the basal ganglia.
- Reduced activity of enzymes including glutamic acid decarboxylase and choline acetyltransferase; decreased substance P levels.
Conclusions:
- Significant neurochemical imbalances are present in Huntington's disease brains.
- Current pharmacologic treatments offer limited improvement over standard neuroleptics.
Abstract:
Huntington's disease (HD), a dominantly inherited disorder of the nervous system, is usually manifest about middle age by dance-like movements. The disorder may occur in children, when epilepsy and rigidity may be the predominant signs. Degeneration of neurons occurs throughout the whole brain, but this is most marked in the basal ganglia. Neurochemical examination of postmortem brain frozen at the time of autopsy has been collected from patients dying with HD and compared with postmortem brain from psychotic patients and cases without neuropsychiatric disease. A number of alterations in neurotransmitters and their biosynthetic enzymes have been found. There are decreased concentrations of the neuroinhibitory transmitter gamma aminobutyric acid and this is associated with increased concentrations of dopamine and serotonin in the basal ganglia. In addition, there is decreased activity of glutamic acid decarboxylase, choline acetyltransferase, angiotensin-converting enzyme, as well as a decreased concentration of the neuropeptide substance P. Various pharmacologic agents have been tried based on the neurochemical alterations, but nothing has been found to be superior to the various neuroleptics in common use.