Abstract
Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the synthesis of serotonin, dopamine, and certain trace amines and is present in a variety of organs including the brain and spinal cord. It is previously reported that in mammalian spinal cord AADC cells (called D-cells) were largely confined to a region around the central canal and that they do not produce monoamines. To date, there has not been a detailed description of their distribution and morphology in mammals. In the present study this issue is systematically investigated using immunohistochemistry. We have found that AADC cells in the rat spinal cord are both more numerous and more widely distributed than previously reported. In the gray matter, AADC neurons immunolabeled for NeuN were not only found in the region around the central canal but also in the dorsal horn, intermediate zone, and ventral horn. In the white matter a large number of glial cells were AADC-immunopositive in different spinal segments and the vast majority of these cells expressed oligodendrocyte and radial glial phenotypes. Additionally, a small number of AADC neurons labeled for NeuN were found in the white matter along the ventral median fissure. The shapes and sizes of AADC neurons varied according to their location. For example, throughout cervical and lumbar segments AADC neurons in the intermediate zone and ventral horn tended to be rather large and weakly immunolabeled, whereas those in comparable regions of sacrocaudal segments were smaller and more densely immunolabeled. The diverse morphological characteristics of the AADC cells suggests that they could be further divided into several subtypes. These results indicate that AADC cells are heterogeneously distributed in the rat spinal cord and they may exert different functions in different physiological and pathological situations.
Highlights
Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the conversion of 5-hydroxytryptophan (5-HTP) to 5-hydroxytryptamine (5-HT, serotonin) and L-dihydroxyphenylalanine (L-dopa) to dopamine (DA) (Lovenberg et al, 1962; Christenson et al, 1972)
Using a sacral 2 (S2) spinal transection rat model (Bennett et al, 1999), we (Wienecke et al, 2014; Ren et al, 2016) and Li et al (2014) have demonstrated that AADC cells below the lesion increase their ability to utilize exogenous 5-HTP or L-dopa to synthesize 5-HT or DA, which could in turn increase motoneuron excitability. These results indicate that AADC cells may serve as a kind of reserve cells playing a critical role in compensating for lost monoamine innervations from the brain, and may be important for motor functional recovery in spinal cord injury (SCI), the overwhelming expression of AADC in capillary pericytes impairs capillary blood flow and motor function (Li et al, 2017)
In the present study we have performed adsorption experiments for rabbit anti-AADC antibody with the antibody pre-adsorbed with whole long AADC recombinant proteins of human origin and the AADC immunolabeling was completely abolished in the sections from the brainstem (Figures 1A,B) and the spinal cord
Summary
Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the conversion of 5-hydroxytryptophan (5-HTP) to 5-hydroxytryptamine (5-HT, serotonin) and L-dihydroxyphenylalanine (L-dopa) to dopamine (DA) (Lovenberg et al, 1962; Christenson et al, 1972). AADC neurons in the brain can be divided into two classes: monoaminergic ( called bienzymatic) and non-monoaminergic ( called monoenzymatic) neurons The former can be further divided into DA-producing and 5-HTproducing neurons depending on whether the neurons contain tyrosine hydroxylase (TH) or tryptophan hydroxylase (TPH) (Hökfelt et al, 1973; Tison et al, 1991; Ugrumov, 2009). In the spinal cord AADC-only cells are called D1-cells, whereas those in other brain regions are designated D2 to D14-cells according to their locations from caudal to rostral (Jaeger et al, 1983, 1984)
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