Aromatic L-amino acid decarboxylase cells in the spinal cord: a potential origin of monoamines.

Abstract

Monoamine neurotransmitters include catecholamines and indoleamines. The most common catecholamines are dopamine (DA), noradrenaline (NA) and adrenaline, which are produced from phenylalanine and tyrosine; whereas the most common indoleamine is serotonin (5-hydroxytrypta mine, 5-HT), which is produced from 5-hydroxytryptophan (5-HTP). In the central nervous system, monoamine neurotransmitters come from specific monoaminergic neurons that occur in a variety of brain regions. In the mammalian spinal cord the different monoamine neurotransmitters, which are important modulators of both sensory and motor functions, are commonly believed to originate in different supraspinal brain regions. For example, 5-HT is produced by neurons in the caudal brain stem raphe nuclei, which include the raphe magnus, raphe obscurus, raphe pallidus, ventral lateral medulla and the area postrema; DA is mainly from the hypothalamic A11 region; and NA is mainly from the locus coeruleus. Traditionally, it has been held that monoamine neurotransmitters cannot be produced in the spinal cord itself. However, following spinal cord transection, some 2–15% of the normal complement of 5-HT and about 5% of the normal complement of NA remain in the spinal cord below the lesion (Magnusson, 1973; Schmidt and Jordan, 2002) although the data about the existence of residual DA are inconsistent to date. For decades, neuroscientists – especially those in the field of spinal cord injury (SCI) research – have been frustrated in their efforts to determine the origins of these small amounts of monoamines. Recently, accumulating evidence has suggested that one possible origin might be the intraspinal monoaminergic neurons. Indeed, some intraspinal 5-HT, tyrosine hydroxylase (TH) and DA β-hydroxylase neurons have been found in mammalian spinal cord (Mouchet et al., 1986; Neuton and Hamill, 1988). However, intraspinal monoaminergic neurons are both very few in number and sparsely distributed. For example, the entire rat spinal cord contains only 3–9 5-HT cells, which occur mainly in regions below the cervical spinal level (Neuton and Hamill, 1988); intraspinal DA cells occur mainly at cervical and sacral levels; and intraspinal NA cells occur mainly in cervical segments (Mouchet et al., 1986). Considering these facts, it seems quite improbable that, following complete spinal transection, intraspinal monoaminergic neurons are the sole source of residual monoamines caudal to the lesion. Then what are the other possible sources? Recent findings by our group (Wienecke et al., 2014) and Bennett's group (Li et al., 2014) point to the aromatic L-amino acid decarboxylase (AADC) cells in the spinal cord.