HMG-CoA synthase isoenzymes 1 and 2 localize to satellite glial cells in dorsal root ganglia and are differentially regulated by peripheral nerve injury.
In dorsal root ganglia (DRG), satellite glial cells (SGCs) tightly ensheathe the somata of primary sensory neurons to form functional sensory units. SGCs are identified by their flattened and irregular morphology and expression of a variety of specific marker proteins. In this report, we present evidence that the 3-hydroxy-3-methylglutaryl coenzyme A synthase isoenzymes 1 and 2 (HMGCS1 and HMGCS2) are abundantly expressed in SGCs. Immunolabeling with the validated antibodies revealed that both HMGCS1 and HMGCS2 are highly colabeled with a selection of SGC markers, including GS, GFAP, Kir4.1, GLAST1, GDNF, and S100 but not with microglial cell marker Iba1, myelin sheath marker MBP, and neuronal marker β3-tubulin or phosphorylated CaMKII. HMGCS1 but not HMGCS2 immunoreactivity in SGCs is reduced in the fifth lumbar (L5) DRGs that contain axotomized neurons following L5 spinal nerve ligation (SNL) in rats. Western blot showed that HMGCS1 protein level in axotomized L5 DRGs is reduced after SNL to 66±8% at 3 days (p<0.01, n=4 animals in each group) and 58±13% at 28 days (p<0.001, n=9 animals in each group) of its level in control samples, whereas HMGCS2 protein was comparable between injured and control DRGs. These results identify HMGCSs as the alternative markers for SGCs in DRGs. Downregulated HMGCS1 expression in DRGs after spinal nerve injury may reflect a potential role of abnormal sterol metabolism of SGCs in the nerve injured-induced neuropathic pain.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China.
Fei
F
Wang
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Orthopedic Surgery, Affiliated Hospitals of Qingdao University, Qingdao 266000, PR China.
Hongfei
H
Xiang
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Gregory
G
Fischer
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Zhen
Z
Liu
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Matthew J
MJ
Dupont
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA.
Quinn H
QH
Hogan
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA. Electronic address: hyu@mcw.edu.
Hongwei
H
Yu
D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000201:enzymology* / Q000293:injuries / Q000473:pathology; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008159:Lumbar Vertebrae; D008297:Male; D009437:Neuralgia / Q000201:enzymology* / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000201:enzymology* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D027161:Satellite Cells, Perineuronal / Q000201:enzymology* / Q000473:pathology; D013127:Spinal Nerves / Q000201:enzymology / Q000293:injuries* / Q000473:pathology
D007527:Isoenzymes; D006904:Hydroxymethylglutaryl-CoA Synthase
Cholesterol; Dorsal root ganglion, peripheral nerve injury; HMG-CoA synthase; Neuropathic pain; Satellite glial cells
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