Lithium chloride could aggravate brain injury caused by 3-nitropropionic acid.
Lithium, a well-known drug for the treatment of bipolar disorder, may also have the ability to reduce neurodegeneration and stimulate cell proliferation. Systemic injection of mitochondrial toxin 3-nitropropionic acid (3NPA) is known to induce a relatively selective, Huntington disease-like brain injury. The aim of this study was to determine the effect of lithium chloride (LiCl) on brain injury caused by 3NPA. Female adult Wistar rats were pre-treated with LiCl (127 mg/kg) 1 day before the first injection of 3NPA (28 mg/kg), and then for 8 days with the same treatment but receiving LiCl 1 hour before 3NPA. Control groups were pre-treated accordingly, with LiCl or with normal saline, but were not treated with 3NPA. Staining for cytochrome c oxidase activity and in situ hybridization autoradiography of synaptotagmin-4 and -7 mRNAs were used to evaluate brain injury caused by 3NPA. There was a significant reduction of body weight in the 3NPA+LiCl group (79%) compared to the 3NPA group (90%, p = 0.031) and both control groups (100%, p = 0.000). Densitometric evaluation of cytochrome c oxidase staining and in situ hybridization autoradiograms revealed that the pre-treatment with LiCl caused an increase in striatal lesion for about 40% (p = 0.049). Moreover, the lesion was observed also in the hippocampus of three animals from the 3NPA+LiCl group and in two animals from the 3NPA group. However, there were no differences between the LiCl and saline group in any of the measured parameters. We concluded that the pre-treatment with a relatively nontoxic dose of LiCl could aggravate brain injury caused by 3NPA.
Institute of Histology and Embryology, Medical Faculty of Ljubljana, University of Ljubljana, Ljubljana. sandramilutinovic@yahoo.com.
Aleksandra
A
Milutinović
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000473:pathology; D018021:Lithium Chloride / Q000633:toxicity*; D017072:Neostriatum / Q000473:pathology; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D050857:Synaptotagmins / Q000096:biosynthesis / Q000235:genetics
D009574:Nitro Compounds; D011422:Propionates; D050857:Synaptotagmins; D003576:Electron Transport Complex IV; D018021:Lithium Chloride; C015392:3-nitropropionic acid