Changes in vesicular glutamate transporter 2, vesicular GABA transporter and vesicular acetylcholine transporter labeling of sacrocaudal motoneurons in the spastic rat.
Spasticity of the midline musculature can significantly hinder performing transfers and lead to development of pressure sores. Currently, significant gaps exist in our knowledge of the pathophysiology involved in spasticity development following SCI, especially regarding the axial musculature. The goals of this study were: (1) to determine the effects of S(2) transection on the number and distribution of glutamatergic, GABAergic and cholinergic inputs on more caudal motoneurons, (2) to correlate these changes with the development of spasticity within the tail musculature, which are the caudal counterparts to the axial musculature. Animals with S(2) spinal transection were tested behaviorally for the progression of spasticity within the tail musculature. At 1, 2, 4, or 12 weeks post-injury, the animals were sacrificed and temporal changes in glutamatergic, GABAergic, and cholinergic inputs to sacrocaudal motoneurons were assessed using antibodies for the specific vesicular transporter of each neurotransmitter and confocal microscopy. At 1 week post-injury, when the tail musculature demonstrated decreased responsiveness, an overall increase in the ratio of excitatory to inhibitory input to sacrocaudal motoneurons was observed. From 2 to 12 weeks post-injury, when the tail musculature demonstrated increased reflex behavior, an overall decrease in the ratio of excitatory to inhibitory inputs was observed. Additionally, from 2 to 12 weeks following spinal transection, a progressive loss of cholinergic labeling of sacrocaudal motoneurons was observed. The increase in the overall level of excitation with a concomitant loss of cholinergic influence following spinal transection could, in part, explain the development of spasticity within the tail musculature.
Kitzman
Patrick
P
Department of Rehabilitation Sciences, The University of Kentucky, 126G Charles T. Wethington Building, 900 S. Limestone Ave., Lexington, 40536-0200, USA. phkitz1@email.uky.edu
D000818:Animals; D002452:Cell Count; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D009046:Motor Neurons / Q000378:metabolism*; D009128:Muscle Spasticity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism*
D050494:Vesicular Acetylcholine Transport Proteins; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C493406:vesicular GABA transporter; D002772:Cholera Toxin