Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease.
Huntington's disease is a progressive, inherited neurodegenerative disorder characterized by the loss of subsets of neurons primarily in the striatum. In this study, we assessed the neuroprotective effect of lithium against striatal lesion formation in a rat model of Huntington's disease in which quinolinic acid was unilaterally infused into the striatum. For this purpose, we used a dopamine receptor autoradiography and glutamic acid decarboxylase mRNA in situ hybridization analysis, methods previously shown to be adequate for quantitative analysis of the excitotoxin-induced striatal lesion size. Here we demonstrated that subcutaneous injections of LiCl for 16 days prior to quinolinic acid infusion considerably reduced the size of quinolinic acid-induced striatal lesion. Furthermore, these lithium pre-treatments also decreased the number of striatal neurons labeled with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Immunohistochemistry and western blotting demonstrated that lithium-elicited neuroprotection was associated with an increase in Bcl-2 protein levels. Our results raise the possibility that lithium may be considered as a neuroprotective agent in treatment of neurodegenerative diseases such as Huntington's disease.
Wei
H
H
Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1363, USA.
Qin
Z H
ZH
Senatorov
V V
VV
Wei
W
W
Wang
Y
Y
Qian
Y
Y
Chuang
D M
DM
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000493:pharmacokinetics; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005968:Glutamate Decarboxylase / Q000235:genetics; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000235:genetics; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D017378:Quinolinic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism
D018692:Antimanic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D007527:Isoenzymes; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D019938:Cyclin D1; D008094:Lithium; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D017378:Quinolinic Acid; D018021:Lithium Chloride