Glucocorticoid receptors are widely expressed in brain, where they are thought to play a role in controlling neurogenesis and to mediate many of the central nervous system effects of stress. In non-neuronal cells, protein phosphatase 5 (PP5) has been found in complexes with heat shock protein 90 and glucocorticoid receptors and may be a negative modulator of glucocorticoid receptor function. In the present study, we used co-immunofluorescence analysis to examine whether PP5 and glucocorticoid receptors are co-expressed at the cellular level in rat brain. In several regions containing major populations of glucocorticoid receptor expressing neurons, PP5 and glucocorticoid receptors were co-localized at the cellular level. These include pyramidal cells of the hippocampal CA1 and CA2 regions and dentate gyrus granule cells, cerebellar Purkinje neurons, cortical pyramidal neurons, neurons of the central nucleus of the amygdala and parvocellular neurons of the hypothalamic paraventricular nucleus. There are also neuronal populations that are stained strongly for glucocorticoid receptors, such as cerebellar granule cells, where PP5 is either absent or below detection limits. Likewise, numerous neuronal populations contain PP5, but not glucocorticoid receptors. Whereas glucocorticoid receptors are expressed in both neurons and glial cells throughout the brain, PP5 appears to be primarily expressed in neurons. These studies suggest that glucocorticoid receptors may be differentially regulated by phosphatase action in different populations of central nervous system cells. Co-localization of PP5 and glucocorticoid receptors in brain regions involved in feedback control of the hypothalamus-pituitary-adrenal axis suggests that PP5 may be an important modulator of glucocorticoid receptor responses in this pathway.
Bibliographical noteFunding Information:
Confocal microscopy data were acquired in the Purdue Cancer Center Analytical Cytometry Laboratories supported by the Cancer Center NCI core grant # NIH NCI-2P30CA23168. The authors gratefully acknowledge the expert assistance of Jennifer Sturgis for confocal image collection and processing, Amanda Mullins for assistance with processing of brain slices and Ling Wang for HeLa cell immunofluorescence staining. This work was supported by NIH grants NS031221 (SR) and DA13680 (RLM).
- Glucocorticoid receptor
- Protein phosphatase 5