title: Temporal changes in glial fibrillary acidic protein messenger RNA and [3H]PK11195 binding in relation to imidazoline-I2-receptor and alpha 2-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat.
abstract: Immunohistochemical studies have demonstrated that following global forebrain ischaemia the selective neuronal loss that occurs in the CA1 pyramidal cell layer of the hippocampus is accompanied by a reactive astrocytosis, characterized by increases in glial fibrillary acidic protein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocampus have been mapped four, eight, 12, 16 and 20 days following 10 min of global forebrain ischaemia in the rat and related to changes in [3H]PK11195 binding to peripheral benzodiazepine receptors, a putative marker of activated microglia. Recent studies have suggested that the imidazoline-I2-receptor, one of a class of non-adrenergic receptors related to, but structurally and functionally distinct from alpha 2-adrenoceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I2-receptor and alpha 2-adrenoceptor binding sites. Following transient ischaemia there was a marked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, peaking four days after ischaemia and then increasing gradually during the remainder of the study period. There was also a sustained increase in [3H]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked four days after ischaemia the density of [3H]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marked increase in glial fibrillary acidic protein messenger RNA levels there was no concomitant alteration in imidazoline-I2-receptor binding sites detected using the specific radioligand, [3H]2-(2-benzofuranyl)-2-imidazoline, although alpha 2-adrenoceptor binding was decreased at eight days after ischaemia and did not recover. The time-course and biphasic nature of the changes in the astrocytic marker, glial fibrillary acidic protein messenger RNA, in the hippocampus following ischaemia may reflect different functions of glial fibrillary acidic protein-reactive astrocytes in the post-ischaemic period. Differences in temporal expression of glial fibrillary acidic protein messenger RNA and [3H]PK11195 binding support the proposed localization of peripheral benzodiazepine receptors on activated microglia, as distinct from reactive astrocytes. There was no evidence in the present study that imidazoline-I2-receptors are functionally linked to glial fibrillary acidic protein expression as the reactive astrocytosis in the hippocampus following ischaemia was not associated with changes in imidazoline-I2-receptor binding site density.
authors.affiliation: University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
authors.forename: E L
authors.initials: EL
authors.lastname: Conway
authors.forename: A L
authors.initials: AL
authors.lastname: Gundlach
authors.forename: J A
authors.initials: JA
authors.lastname: Craven
mesh_terms: D000818:Animals; D001345:Autoradiography; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D054755:Imidazoline Receptors; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D054755:Imidazoline Receptors; D007546:Isoquinolines; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C037850:PK 11195