Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system.
By means of a monoclonal mouse immunoglobulin G2a antibody against the rat liver glucocorticoid receptor and the indirect immunoperoxidase technique, the distribution of glucocorticoid receptors in neuronal and glial cell populations was mapped in the central nervous system of the male rat. The mapping was complemented by computer-assisted morphometric and microdensitometric evaluation of glucocorticoid receptor immunoreactivity in many brain regions. The quantitative analysis allowed us to achieve for the first time an objective characterization of glucocorticoid receptor distribution in the CNS, thus avoiding the ambiguities of previous mapping studies based on subjective evaluations. In addition, a taxonomic analysis of central nervous system regions containing glucocorticoid receptor immunoreactivity was carried out utilizing the quantitative parameters obtained in the morphometric evaluation. Nuclei of neuronal and glial cells containing glucocorticoid receptor immunoreactivity were detected in a widespread, but still highly heterogeneous, fashion in the central nervous system, underlining the view that glucocorticoids can control a large number of central nervous system target cells via effects on gene expression. Many nerve cell populations have been shown to contain substantial amounts of nuclear glucocorticoid receptor immunoreactivity, whereas only a low density of glial cells, in both gray and white matter, show nuclear glucocorticoid receptor immunoreactivity. Thus, in most brain areas, the major target for glucocorticoids appears to be the nerve cells. Interestingly, an inverse correlation was found in the regional density of glucocorticoid receptor-immunoreactive nerve and glial cells, suggesting that glucocorticoids may influence a brain area either via glial cells or, more frequently, via nerve cells. The results on mapping highlight the impact of glucocorticoids in areas both traditionally and not traditionally involved in stress responses. The distribution of glucocorticoid receptor immunoreactivity also emphasizes a role of glucocorticoids in the regulation of the afferent regions of the basal ganglia and the cerebellar cortex, and of both afferent and efferent layers of the cerebral cortex. Glucocorticoid receptor immunoreactivity is widely distributed over the thalamus, probably leading to modulation of activity in the various thalamocortical pathways transmitting inter alia specific sensory information to the cerebral cortex. Many unspecific afferents to the cerebral cortex are potentially regulated by glucocorticoid receptors such as the noradrenaline and 5-hydroxytryptamine afferents, since their nerve cells of origin contain strong glucocorticoid receptor immunoreactivity. Eight brain regions involving sensory, motor and limbic areas were shown to have a similarity with regard to glucocorticoid receptor-immunoreactive parameters at the level of 95%. The density of glucocorticoid receptor-immunoreactive nerve cells appeared to be the main factor in determining such a very high level of similarity. Overall, our results emphasize that glucocorticoids may appropriately tune networks of different areas to obtain optimal integration and in this way improve survival of the animal under challenging conditions.
Cintra
A
A
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Zoli
M
M
Rosén
L
L
Agnati
L F
LF
Okret
S
S
Wikström
A C
AC
Gustaffsson
J A
JA
Fuxe
K
K
D000315:Adrenalectomy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001923:Brain Chemistry; D001931:Brain Mapping; D002490:Central Nervous System / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000503:physiopathology; D003345:Corticosterone / Q000494:pharmacology; D003720:Densitometry; D005938:Glucocorticoids / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009457:Neuroglia / Q000737:chemistry* / Q000648:ultrastructure; D009473:Neuronal Plasticity; D009474:Neurons / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats / Q000033:anatomy & histology* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D013047:Specific Pathogen-Free Organisms; D013312:Stress, Physiological / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D011965:Receptors, Glucocorticoid; D003345:Corticosterone