title: Production of Dopamine by Aromatic l-Amino Acid Decarboxylase Cells after Spinal Cord Injury.
abstract: 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 (5-hydroxytryptamine) from 5-hydroxytryptophan after spinal cord injury (SCI). Because AADC is a common enzyme catalyzing 5-hydroxytryptophan to serotonin and l-3,4-dihydroxyphenylalanine (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 or not this is the case, a similar rat sacral SCI model and a similar experimental paradigm were adopted as that which we had used previously. In the chronic SCI rats (> 45 days), 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 becoming 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 fivefold over the baseline level. When pretreated with a central AADC inhibitor (NSD-1015), 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.
authors.affiliation: 1 Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen, Denmark .|2 Laboratory of Spinal Injury and Rehabilitation, Chengde Medical University , Chengde, China .
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Ren
authors.affiliation: 1 Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen, Denmark .|3 Department of Nutrition, Exercise, and Sports, University of Copenhagen , Copenhagen, Denmark .
authors.forename: Jacob
authors.initials: J
authors.lastname: Wienecke
authors.affiliation: 1 Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen, Denmark .|2 Laboratory of Spinal Injury and Rehabilitation, Chengde Medical University , Chengde, China .
authors.forename: Hans
authors.initials: H
authors.lastname: Hultborn
authors.affiliation: 1 Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen, Denmark .|4 Neuronano Research Center, Department of Experimental Medical Sciences, Lund University , Lund, Sweden .
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors / Q000494:pharmacology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D007980:Levodopa; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine
keywords: l-dopa; monoamine; motoneuron; spasticity; spinal cord