title: Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina.
abstract: There is accumulating evidence that glutamate and GABA release are key mechanisms of ischaemic events in the CNS. However, data on the expression of involved transporters for these mediators are inconsistent, potentially impeding further neuroprotective approaches. Here, we applied immunofluorescence labelling to characterise the expression pattern of vesicular glutamate (VGLUT) and GABA transporters (VGAT) after acute focal cerebral ischaemia and in two models of retinal ischaemia. Mice were subjected to filament-based focal cerebral ischaemia predominantly involving the middle cerebral artery territory, also leading to retinal ischaemia due to central retinal artery occlusion (CRAO). Alternatively, retinal ischaemia was induced by a transient increase of the intraocular pressure (HIOP). One day after ischaemia onset, diminished immunolabelling of neuronal nuclei and microtubule-associated protein 2-positive structures were found in the ipsilateral neocortex, subcortex and the retina, indicating neuronal degeneration. VGLUT1 expression did not change significantly in ischaemic tissues whereas VGLUT2 was down-regulated in specific areas of the brain. VGLUT3 expression was only slightly down-regulated in the ischaemia-affected neocortex, and was found to form clusters on fibrils of unknown origin in the ischaemic lateral hypothalamus. In contrast, retinae subjected to CRAO or HIOP displayed a rapid loss of VGLUT3-immunoreactivity. The expression of VGAT appears resistant to ischaemia as there was no significant alteration in all the regions analysed. In summary, these data indicate a region- and subtype-specific change of VGLUT expression in the ischaemia-affected CNS, whose consideration might help to generate specific neuroprotective strategies.
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany. dominik.michalski@medizin.uni-leipzig.de
authors.forename: D
authors.initials: D
authors.lastname: Michalski
authors.forename: W
authors.initials: W
authors.lastname: Härtig
authors.forename: K
authors.initials: K
authors.lastname: Krügel
authors.forename: R H
authors.initials: RH
authors.lastname: Edwards
authors.forename: M
authors.initials: M
authors.lastname: Böddener
authors.forename: L
authors.initials: L
authors.lastname: Böhme
authors.forename: T
authors.initials: T
authors.lastname: Pannicke
authors.forename: A
authors.initials: A
authors.lastname: Reichenbach
authors.forename: A
authors.initials: A
authors.lastname: Grosche
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D051379:Mice; D016548:Prosencephalon / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012171:Retinal Vessels; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D050496:Vesicular Glutamate Transport Proteins