The role of dopamine in Huntington's disease.

TitleThe role of dopamine in Huntington's disease.
Publication TypeJournal Article
Year of Publication2014
AuteursCepeda, C, Murphy, KPS, Parent, M, Levine, MS
JournalProg Brain Res
Volume211
Pagination235-54
Date Published2014
ISSN1875-7855
KeywordsAnimals, Dopamine, Humans, Huntington Disease, Synaptic Transmission
Abstract

Alterations in dopamine (DA) neurotransmission in Parkinson's disease are well known and widely studied. Much less is known about DA changes that accompany and underlie some of the symptoms of Huntington's disease (HD), a dominant inherited neurodegenerative disorder characterized by chorea, cognitive deficits, and psychiatric disturbances. The cause is an expansion in CAG (glutamine) repeats in the HTT gene. The principal histopathology of HD is the loss of medium-sized spiny neurons (MSNs) and, to a lesser degree, neuronal loss in cerebral cortex, thalamus, hippocampus, and hypothalamus. Neurochemical, electrophysiological, and behavioral studies in HD patients and genetic mouse models suggest biphasic changes in DA neurotransmission. In the early stages, DA neurotransmission is increased leading to hyperkinetic movements that can be alleviated by depleting DA stores. In contrast, in the late stages, DA deficits produce hypokinesia that can be treated by increasing DA function. Alterations in DA neurotransmission affect glutamate receptor modulation and could contribute to excitotoxicity. The mechanisms of DA dysfunction, in particular the increased DA tone in the early stages of the disease, are presently unknown but may include initial upregulation of DA neuron activity caused by the genetic mutation, reduced inhibition resulting from striatal MSN loss, increased excitation from cortical inputs, and DA autoreceptor dysfunction. Targeting both DA and glutamate receptor dysfunction could be the best strategy to treat HD symptoms.

DOI10.1016/B978-0-444-63425-2.00010-6
Alternate JournalProg. Brain Res.
PubMed ID24968783
PubMed Central IDPMC4409123
Grant ListR01 NS041574 / NS / NINDS NIH HHS / United States
R21 NS081335 / NS / NINDS NIH HHS / United States
R21 NS078633 / NS / NINDS NIH HHS / United States
NS78633 / NS / NINDS NIH HHS / United States
NS41574 / NS / NINDS NIH HHS / United States