Robust upregulation of serotonin 2A receptors after chronic spinal transection of rats: An immunohistochemical study

TY - JOUR

T1 - Robust upregulation of serotonin 2A receptors after chronic spinal transection of rats: An immunohistochemical study

AU - Kong, Xiang-Yu

AU - Wienecke, Jacob

AU - Hultborn, Hans

AU - Zhang, Mengliang

N1 - Keywords: Animals; Choline O-Acetyltransferase; Chronic Disease; Dendrites; Immunohistochemistry; Male; Microscopy, Confocal; Microscopy, Fluorescence; Motor Neurons; Neurons; Photomicrography; Random Allocation; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Sacrum; Serotonin; Spinal Cord Injuries; Up-Regulation

PY - 2010/3/12

Y1 - 2010/3/12

N2 - It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan. This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and also in the development of symptoms such as hyperreflexia and spasticity. However, the mechanisms of this denervation supersensitivity are still largely unknown. In this study we have investigated the changes in 5-HT2A receptor immunoreactivity following chronic spinal transections at the level of the sacrocaudal spinal cord. The results show that in the spinalized rats the immunoreactivity of 5-HT2A receptors below the lesion is dramatically increased in the motoneuron soma and its proximal dendritic territory, most likely also in their distal dendritic territory, to a level 3-5-fold higher than that of sham-operated rats. We also found a small number of intraspinal 5-HT neurons and clusters of 5-HT fibers and their varicosities in the spinal cord caudal to the lesion, which may provide an intrinsic source of 5-HT to act upon the upregulated 5-HT2A receptors. These results indicate that the upregulation of 5-HT2A receptors at least partly underlies the 5-HT denervation supersensitivity of spinal motoneurons after a complete spinal transection.

AB - It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan. This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and also in the development of symptoms such as hyperreflexia and spasticity. However, the mechanisms of this denervation supersensitivity are still largely unknown. In this study we have investigated the changes in 5-HT2A receptor immunoreactivity following chronic spinal transections at the level of the sacrocaudal spinal cord. The results show that in the spinalized rats the immunoreactivity of 5-HT2A receptors below the lesion is dramatically increased in the motoneuron soma and its proximal dendritic territory, most likely also in their distal dendritic territory, to a level 3-5-fold higher than that of sham-operated rats. We also found a small number of intraspinal 5-HT neurons and clusters of 5-HT fibers and their varicosities in the spinal cord caudal to the lesion, which may provide an intrinsic source of 5-HT to act upon the upregulated 5-HT2A receptors. These results indicate that the upregulation of 5-HT2A receptors at least partly underlies the 5-HT denervation supersensitivity of spinal motoneurons after a complete spinal transection.

U2 - 10.1016/j.brainres.2010.01.030

DO - 10.1016/j.brainres.2010.01.030

M3 - Journal article

C2 - 20085755

SN - 0006-8993

VL - 1320

SP - 60

EP - 68

JO - Brain Research

JF - Brain Research

ER -