Aromatic L‐amino acid decarboxylase in rat corpus striatum

Abstract

We studied the distribution of aromatic L-amino acid decarboxylase (AAAD) activity in striatal compartments of rats. After near-total destruction of nigrostriatal dopaminergic neurons, 15 to 20% of the initial enzyme activity remained. Striatal enzyme activity remained unchanged after destruction of serotoninergic terminals by electrolytic raphe lesions. Combined raphe-nigrostriatal lesions or nigrostriatal lesions alone produced similar decreases in striatal decarboxylase. Intrastriatal injection of kainic acid (which selectively destroys striatal interneurons and efferent neurons and also induces marked glial proliferation) reduced activity by 20%. Only 7% of initial striatal activity (perhaps localized in capillaries) remained after combined nigrostriatal-kainic acid lesions. These findings indicate that after degeneration of dopaminergic terminals, striatal interneurons and efferent neurons, but not serotonergic terminals of glia, contain an important fraction of the residual AAAD. This compartment may be the site of enzymatic conversion of exogenous L-dopa to dopamine in the parkinsonian striatum.

Effect of age and disease duration on parkinsonian motor scores under levodopa therapy

“…Availability of endogenous dopamine and dopamine receptor density decline with increasing age (Marksman et al, 1979;Cot6 and Kremzner, 1983;De Keyser et al, 1990;Martin et al, 1989) and the combined age-and disease-related changes in the dopaminergic neurotransmission might insufficiently be compensated by dopaminergic therapy (Lloyd and Hornykiewicz, 1970;Lloyd et al, 1975;Melamed et al, 1981;Leenders et al, 1986;Hornykiewicz and Kish, 1986;Ahlskog et al, 1991;Brooks et al, 1992).…”

Pathophysiology of levodopa-induced dyskinesia: Potential for new therapies

“…However, the site of levodopa decarboxylation in the parkinsonian brain remains obscure, as most striatal dopamine terminals have degenerated. It was initially assumed that levodopa administration enhances dopamine synthesis and release in the surviving nigrostriatal neurons 4,20 , but subsequent studies have shown that exogenous levodopa might be decarboxylated and released as dopamine by serotonin terminals, striatal capillaries, noradrenergic neurons and non-aminergic striatal interneurons [46][47][48][49] . Although the specific decarboxylation site remains open to debate, it is possible that these nondopamine terminals and neurons are involved in the occurrence of LID.…”

Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.

“…Ten patients had been on levodopa for up to 5 years (six described stable motor totor response in Parkinson's disease 719 function, two had symptoms of moderate motor fluctuations and two complained of severe oscillations), eight for between six and 10 years (one stable, four moderate and three severe), and 13 for greater than 10 …”