L-Dihydroxyphenylalanine (L-DOPA) [G-BSA]

Dopamine is involved in many important brain functions, including voluntary motor movement. Dysfunction of the dopaminergic system can induce motor impairments, including Parkinson's disease. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. In the present study, we investigated neuronal activity in hippocampal subregions during hyperactivity by measuring Fos expression levels using immunohistochemistry.Dopamine-deficient mice were maintained on daily intraperitoneal injections of 50 mg/kg L-DOPA. Seventy-two hours after the last L-DOPA injection, DD mice were exposed to a novel environment for 1, 2, or 4 h, and then brains were collected. In wildtype mice, the number of Fos-immunopositive neurons significantly increased in the hippocampal CA1 region after 1 h of exposure to the novel environment and then decreased. In DD mice, the number of Fos-immunopositive neurons gradually increased and then significantly increased after 4 h of exposure to the novel environment. The number of Fos-immunopositive neurons also significantly increased in the CA3 region and dentate gyrus in DD mice after 4 h of exposure to the novel environment. These results indicate that the delayed and prolonged excitation of hippocampal neurons in the CA1, CA3, and dentate gyrus that is caused by dopamine depletion might be involved in hyperactivity in DD mice.

Dopa-responsive dystonia (DRD) is a complex genetic disorder with either autosomal dominant or autosomal recessive inheritance, with autosomal dominant being more frequent. Autosomal dominant DRD is known to be caused by mutations in the GCH1 gene, with incomplete penetrance frequently reported, particularly in males. Here, we report a male patient with DRD caused by exon 1 deletion in the GCH1 gene inherited from the asymptomatic mother. The patient had an atypical presentation, notably with no dystonia, and underwent extensive workup for a myriad of neuromuscular disorders before a low-dose L-dopa trial and confirmatory genetic testing were performed. Our experience with this family highlights an atypical presentation of DRD and prompts us to consider the genetic complexity of DRD.