Vesicular dysfunction during experimental thiamine deficiency is indicated by alterations in dopamine metabolism.
Experimental and clinical studies indicate that catecholamines play an important role in the neurobehavioural symptomatology of thiamine deficiency. Given the cerebral region-selective vulnerability and the behavioural impairment commonly encountered in thiamine deficiency, we undertook to investigate regional catecholamine metabolism in the brains of pyrithiamine-induced thiamine-deficient rats. Dopamine metabolism was unaffected in the striatum. In contrast, other regions also known to be involved in sensory processing and intellectual function (e.g., frontal cortex, hypothalamus, thalamus), but having a greater noradrenergic input, had increased levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and decreased levels of other dopaminergic metabolites including noradrenaline. In these regions levels of the vesicular amine transporter, defined by tetrabenazine-sensitive [3H]ketanserin binding, were also decreased. Our data suggest a region-selective vesicular dysfunction resulting in intraneuronal release, and subsequent degradation, of dopamine. These disruptions of dopamine and consequently noradrenaline metabolism may account for certain neurobehavioural deficits commonly encountered in thiamine deficiency.
Mousseau
D D
DD
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Canada.
Rao
V L
VL
Butterworth
R F
RF
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011745:Pyrithiamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013747:Tetrabenazine / Q000494:pharmacology; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D000963:Antimetabolites; D002395:Catecholamines; D012702:Serotonin Antagonists; D011745:Pyrithiamine; D007650:Ketanserin; D004298:Dopamine; D009638:Norepinephrine; D013747:Tetrabenazine