TGF-β1 And Golgi Apparatus Alteration In Ischemic And Minocycline Treated Gerbils And Subcellular Compartmentalization Of TGF-β1 In Golgi Apparatus

Objective: Minocycline has been shown to produce neuroprotection inexperimental ischemic stroke. TGF-β1 is an important cytokine in the brain,which increased after ischemia. Golgi apparatus(GA) is a very importantorganelle that involves in the metabolism of numerous proteins. Little isknown, however, about the alteration of GA after ischemia and subcellularcompartmentalization of TGF-β1 in neurons. Therefore, our present studywas designed to check for neuroprotection mechanism of minocycline, GAmorphological alterations and TGF-β1 subcellular localization in the brainafter ischemia.Methods: Gerbils models of bilateral carotid artery occlusion (BCAO)were established by occluding both carotid arteries for 10 min. Minocyclinetreated subjects were injected with a dose (45 mg/kg i.p, BID.) of theminocycline, starting 1 day before the ischemic episode till sacrificed.Histological alteration and TGF-β1,GA immunoreactivities were examinedin the brain tissue after 10 minutes transient forebrain ischemia in gerbils.Confocal Immunofluorographs of TGF-β1 and TGN38 were also taken ingerbils models postocclusion.Results: Results indicated that treatment with minocycline reducedhippocampal damage and TGF-β1 expression. No fragmentation of GAwas found in gerbils 6,24 and 72h postocclusion, but some of the cortical cells showed fragmentation of GA in gerbils 7 days postocclusion.TGF-β1was colocalized with TGN38,a marker molecule for the GA.Conclusions:1. Treatment with minocycline provided a significant neuroprotectionagainst brain ischemia and minocycline may exert neuroprotection bydecreasing expression of TGF-β1.2. GA of the cortex in gerbils models 6, 24 and 72h postocclusionshowed normal profiles.For cortical cells from gerbils survived 7 dayspostocclusion, most of the GA were normal, but some of the cortical cellsshowed fragmentation of GA.3. TGF-β1 was presented in the Golgi apparatus, suggesting that bothcontinuous protein synthesis and transportation via the Golgi complex wererequired for TGF-β1 secretion and TGF-β1 may be essential forphysiological functions involving GA...