DHEA improves symptomatic treatment of moderately and severely impaired MPTP monkeys.
The steroid dehydroepiandrosterone (DHEA) is abundant in men and women and decreases rapidly during aging. Parkinson's disease (PD) is the second most common neurodegenerative disorder just behind Alzheimer. l-3,4-Dihydroxyphenylalanine (l-Dopa) therapy remains the most effective treatment but many patients develop motor complications. This study investigated the acute effect of DHEA alone and with l-Dopa in 12 females monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model PD. DHEA administration alone improved the mean parkinsonian score at 1, 5 and 15mg/kg in moderately and severely impaired MPTP monkeys and increased blood DHEA concentrations. DHEA with a low dose of l-Dopa increased the l-Dopa effect in moderately and severely impaired MPTP monkeys. DHEA lengthened duration of the effect of the low dose of l-Dopa by 15-45min. DHEA at 1, 5 and 15mg/kg combined with a high dose of l-Dopa did not increase dyskinesias. DHEA could act by reducing inhibitory GABAergic activity in the striatal output pathways. DHEA could also be metabolized into estradiol in the brain and increase acutely dopamine activity.
Bélanger
Nancy
N
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), 2705 Laurier Boulevard, Que., Canada G1V 4G2.
Grégoire
Laurent
L
Bédard
Paul J
PJ
Di Paolo
Thérèse
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008252:Macaca fascicularis; D009043:Motor Activity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D012720:Severity of Illness Index
D000978:Antiparkinson Agents; D003687:Dehydroepiandrosterone; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine