Alteration of Bcl-2 expression in the nigrostriatal system after kainate injection with or without melatonin co-treatment.
In order to understand further the role of the anti-apoptotic Bcl-2 proto-oncogene protein in excitotoxin-induced brain injury and possible interaction between Bcl-2 and the antioxidant melatonin, the expression of Bcl-2 in various brain parts was studied after intrastriatal injection of kainate (KA, 2.5 nmol) with or without co-treatment of melatonin (10 mg/kg, intraperitoneally (i.p.)). Three days after unilateral injection of KA to the striatum in the rat, a dramatic direct cytotoxic effect was observed, as indicated an expression of Bcl-2 immunoreactivity in TUNEL- and OX-42-positive cells in the KA-injected striatum and traumatized cortical region. A less severe detrimental effect was also observed in the ipsilateral substantia nigra and peritraumatic cortex, as reflected by an upregulation of Bcl-2-immunostained neurons. Surprisingly, a reduction in Bcl-2-immunoreactive neurons that was accompanied by a less severe loss of tyrosine hydroxylase-immunoreactive neurons in the nigrostriatal pathway was observed after co-treatment with melatonin. Western blot analysis confirmed that Bcl-2 expression is elevated in striatum and cortex on the lesioned side, and that its expression was attenuated substantially after systemic administration of melatonin. The results showing an upregulation of Bcl-2 in nigral neurons and reactive microglia after KA lesion are consistent with the view that Bcl-2 is protective in function in the central nervous system.
Chuang
J I
JI
Department of Physiology, National Cheng Kung University, Taiwan 701, Taiwan, ROC.
Chen
S T
ST
Chang
Y H
YH
Jen
L S
LS
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000975:Antioxidants / Q000494:pharmacology*; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000975:Antioxidants; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D018690:Excitatory Amino Acid Agonists; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051926:Basigin; D014446:Tyrosine 3-Monooxygenase; D008550:Melatonin; D007608:Kainic Acid