TEMPORAL CHANGES IN GLIAL FIBRILLARY ACIDIC PROTEIN MESSENGER-RNA AND[H-3] PK11195 BINDING IN RELATION TO IMIDAZOLINE-I-2-RECEPTOR AND ALPHA(2)-ADRENOCEPTOR BINDING IN THE HIPPOCAMPUS FOLLOWING TRANSIENT GLOBAL FOREBRAIN ISCHEMIA IN THE RAT
El. Conway et al., TEMPORAL CHANGES IN GLIAL FIBRILLARY ACIDIC PROTEIN MESSENGER-RNA AND[H-3] PK11195 BINDING IN RELATION TO IMIDAZOLINE-I-2-RECEPTOR AND ALPHA(2)-ADRENOCEPTOR BINDING IN THE HIPPOCAMPUS FOLLOWING TRANSIENT GLOBAL FOREBRAIN ISCHEMIA IN THE RAT, Neuroscience, 82(3), 1998, pp. 805-817
Immunohistochemical studies have demonstrated that following global fo
rebrain ischaemia the selective neuronal loss that occurs in the CA1 p
yramidal cell layer of the hippocampus is accompanied by a reactive as
trocytosis, characterized by increases in glial fibrillary acidic prot
ein, and activation of microglia. In this study the spatial changes in
glial fibrillary acidic protein messenger RNA levels in the hippocamp
us have been mapped four, eight, 12, 16 and 20 days following 10 min o
f global forebrain ischaemia in the rat and related to changes in [H-3
]PK11195 binding to peripheral benzodiazepine receptors, a putative ma
rker of activated microglia. Recent studies have suggested that the im
idazoline-I-2-receptor, one of a class of non-adrenergic receptors rel
ated to, but structurally and functionally distinct from alpha(2)-adre
noceptors, 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-I-2-receptor and alpha(2)-a
drenoceptor binding sites. Following transient ischaemia there was a m
arked, biphasic increase in glial fibrillary acidic protein messenger
RNA levels throughout the vulnerable CA1 region of the hippocampus, pe
aking four days after ischaemia and then increasing gradually during t
he remainder of the study period. There was also a sustained increase
in [H-3]PK11195 binding, however, in contrast to the initial increase
in glial fibrillary acidic protein messenger RNA levels that peaked fo
ur days after ischaemia the density of [H-3]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 marke
d increase in glial fibrillary acidic protein messenger RNA levels the
re was no concomitant alteration in imidazoline-I-2-receptor binding s
ites detected using the specific radioligand, [H-3]2-(2-benzofuranyl)-
2-imidazoline, although alpha(2)-adrenoceptor binding was decreased al
eight days after ischaemia and did not recover. The time-course and b
iphasic nature of the changes in the astrocytic marker, glial fibrilla
ry acidic protein messenger RNA, in the hippocampus following ischaemi
a may reflect different functions of glial fibrillary acidic protein-r
eactive astrocytes in the post-ischaemic period. Differences in tempor
al expres sion of glial fibrillary acidic protein messenger RNA and [H
-3]PK11195 binding support the proposed localization of peripheral ben
zodiazepine receptors on activated microglia, as distinct from reactiv
e astrocytes. There was no evidence in the present study that imidazol
ine I-2-receptors are functionally linked to glial fibrillary acidic p
rotein expression as the reactive astrocytosis in the hippocampus foll
owing ischaemia was not associated with changes in imidazoline-I-2-rec
eptor binding site density. (C) 1997 IBRO.