Production of dopamine by aromatic L-amino acid decarboxylase cells after spinal cord injury

Research output: Contribution to journalJournal articleResearchpeer-review

Aromatic L-amino acid decarboxylase (AADC) cells are widely distributed in the spinal cord and their functions are largely unknown. We have previously found that AADC cells in the spinal cord could increase their ability to produce serotonin from 5-hydroxytryptophan after spinal cord injury (SCI). Since AADC is a common enzyme catalyzing 5-hydroxytryptophan to serotonin and L-dopa to dopamine (DA), it seems likely that the ability of AADC cells using L-dopa to synthesize DA is also increased. To prove whether this is the case a same rat sacral SCI model and a similar experimental paradigm were adopted as we used previously (Wienecke et al., J. Neurosci. 34, 11984, 2014). In the chronic SCI rats (> 45d), no AADC cells expressed DA if there was no exogenous L-dopa application. However, following administration of a peripheral AADC inhibitor (carbidopa) with or without a monoamine oxidase inhibitor (pargyline) co-application, systemic administration of L-dopa resulted in ~ 94% of AADC cells to become DA-immunopositive in the spinal cord below the lesion, whereas in normal or sham-operated rats none or very few of AADC cells became DA-immunopositive with the same treatment. Using tail electromyography, spontaneous tail muscle activity was increased nearly 5-fold over the baseline level. When pretreated with a central AADC inhibitor (NSD1015), further application of L-dopa failed to increase the motoneuron activity although the expression of DA in the AADC cells was not completely inhibited. These findings demonstrate that AADC cells in the spinal cord below the lesion gain the ability to produce DA from its precursor in response to SCI. This ability also enables the AADC cells to produce 5-HT and trace-amines, and likely contributes to the development of hyperexcitability. These results might also be implicated for revealing the pathological mechanisms underlying L-dopa-induced dyskinesia in Parkinson's disease.

Original languageEnglish
JournalJournal of Neurotrauma
Issue number12
Pages (from-to)1150-1160
Number of pages11
Publication statusPublished - 2016

ID: 154798998