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-o ncogene protein in excitotoxin-induced brain injury and possible interactio n between Bcl-2 and the antioxidant melatonin, the expression of Bcl-2 in v arious brain parts was studied after intrastriatal injection of kainate (KA , 2.5 nmol) with or without co-treatment of melatonin (10 mg/kg, intraperit oneally (i.p.)). Three days after unilateral injection of KA to the striatu m in the rat, a dramatic direct cytotoxic effect was observed, as indicated an expression of Bcl-2 immunoreactivity in. TUNEL- and OX-42-positive cell s in the KA-injected striatum and traumatized cortical region. A less sever e detrimental effect was also observed in the ipsilateral substantia nigra and peritraumatic cortex, as reflected by an upregulation of Bcl-2-immunost ained neurons. Surprisingly, a reduction in Bcl-2-immunoreactive neurons th at was accompanied by a less severe loss of tyrosine hydroxylase-immunoreac tive neurons in the nigrostriatal pathway was observed after co-treatment w ith melatonin. Western blot analysis confirmed that Bcl-2 expression is ele vated in striatum and cortex on the lesioned side, and that its expression was attenuated substantially after systemic administration of melatonin. Th e results showing an upregulation of Bcl-2 in nigral neurons and reactive m icroglia after KA lesion are consistent with the view that Bcl-2 is protect ive in function in the central nervous system. (C) 2001 Elsevier Science B. V. All rights reserved.