re glutamate and huntingtons

john wagstaff jw0207 at
Sat Oct 15 14:55:07 EST 1994

Lyn Frumkin (lrfrum at wrote:

: Huntingtons chorea has not been associated with significant alterations 
: in glutamate, which is not thought to play a role in the pathophysiology 
: of this disease. Caudate atrophy is associated with reductions in GABA and 
: substance P. There is also localized reductions in acetylcholine and 
: cholecystokinin, with overactivity of basal gangla dopamine due to loss 
: of cholinergic inhibition neurons. Thus, while glutamate antagonists are 
: being evaluated for some neurologic diseases, particulary stroke and 
: epilepsy, there is no work assessing these agents in Huntingtons disease.
: HD still remains untreatable and progressive, although dopamine antagonists 
: [e.g. Haldol] decrease the severity of the choreic movements in selected
: patients by blocking excess dopamine.

: Regards,

: Lyn Frumkin, MD, PhD/Neurology

I did not to imply that glutamate was the cause of Huntington's disease,
but most animal models of Huntington's involove intrastriatal
administration of an excitotoxin such as ibotenic or kainic acid, which
glutamate receptor agonists.  These compounds result in somewhat selective
destruction of neurons with cell bodies within the striatum, sparing
neurons that terminate in the striatum (dopamine), another interesting
aspect of these lesions are that NPY/Somatostatin/NADPH positive neurons
are relatively spared, as they are in Huntington's.  So while gluatamate
may not be altered in Huntington's patients, my bet
would be that it is involved somewher in the disease process.

John Wagstaff
Pharmacology and Toxicology
University of Utah

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