Vascular insult accompanied by overexpressed heme oxygenase-1 as a pathophysiological mechanism in experimental neurolathyrism with hind-leg paraparesis.
Neurolathyrism (NL) is a motor neuron disease characterized by spastic paraparesis in the hind legs. β-N-oxalyl-l-α,β-diaminopropionic acid (l-β-ODAP), a component amino acid of the grass pea (Lathyrus sativus L.), has been proposed as the cause of this disease. In our NL rat model, we previously reported that transient intra-parenchymal hemorrhage occurred in the lower spinal cord during the early treatment period. We show here a possible pathological role of the hemorrhage in motor neuron damage and paraparesis pathology. In the lumbo-sacral spinal cord, blood vessel integrity was lost with numerous TdT-mediated dUTP nick end-labeling-positive blood vessel-like structures occurring simultaneously with the hemorrhage. We observed a coincident >10-fold increase in heme oxygenase-1 (HO-1) only in the lower spinal cord. The early period of paraparesis in the lower leg was greatly suppressed by pretreatment with zinc protoporphyrin IX, a HO-1 inhibitor. In vitro, l-β-ODAP was toxic to human umbilical vein endothelial cells compared to l-glutamate. The present data shed light on the role and the mechanism of vascular insult in causing dysfunction and moribund motor neurons in experimental NL.
Laboratory of Biochemistry, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Chiba 274-8555, Japan.
Kimino
K
Kawaguchi
Fernand
F
Lambein
Kuniko
K
Kusama-Eguchi
D000818:Animals; D001808:Blood Vessels / Q000201:enzymology / Q000293:injuries; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications* / Q000201:enzymology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007842:Lathyrism / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008161:Lumbosacral Region; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology; D020335:Paraparesis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000633:toxicity
C510363:3-N-oxalyl-L -2,3-diaminopropanoic acid; D015091:beta-Alanine; D051547:Heme Oxygenase-1