Mineralocorticoid and glucocorticoid receptor expressions in astrocytes and microglia in the gerbil hippocampal CA1 region after ischemic insult
Introduction
The hippocampus is involved in episodic, declarative, spatial and contextual learning and memory. It is a particularly vulnerable and sensitive region of the brain that expresses high levels of adrenal steroid “stress” hormone receptors (McEwen, 1999, Bohbot et al., 2000). Corticosteroid hormones entering the brain can bind to two intracellular receptor types that regulate the transcriptions of responsive genes, i.e., (i) high affinity mineralocorticoid receptors and (ii) glucocorticoid receptors; the latter are bound with approximately 10-fold lower affinity. Glucocorticoid hormones terminate stress response via a negative feedback action at the levels of the pituitary, hypothalamus and limbic brain areas, the latter of which includes the hippocampus, amygdala and septum (Kawata et al., 2001, Kellendonk et al., 2002).
Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are abundantly expressed in the hippocampus, which makes this region a prime target for glucocorticoid action (Aronsson et al., 1988, Reul et al., 1989, De Kloet, 1995). Moreover, excessive GR activation increases hippocampal neuronal vulnerability to neuronal insults such as excitotoxicity, oxidative stress and ischemia (Sapolsky et al., 1988, Goodman et al., 1996, McCullers et al., 2002). Furthermore, protection from delayed neuronal death in transient global ischemia, focal ischemia and kainate-induced excitotoxic damage occurs when stress-induced glucocorticoid release is prevented by administering metyrapone, an inhibitor of steroid 11β hydroxylation (Smith-Swintosky et al., 1996). It has been reported that hypoxic injury-induced impairment in synaptic transmission in the CA1 region in vitro was exacerbated by concomitant corticosteroid treatment and alleviated by pretreatment with metyrapone (Kruggers et al., 1999, Kruggers et al., 2000). This result suggests that synaptic function along with cellular integrity is preserved after hypoxic injury by preventing the ischemia-evoked rise in corticosteroid levels.
Although the actions of glucocorticoids may be important in ischemic damage, changes in the expressions of MR and GR have not been determined in the ischemic hippocampus. Therefore, we examined the ischemia-related changes of MR and GR in the gerbil hippocampus after 5 min of transient forebrain ischemia.
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Experimental animals
This study used the progeny of Mongolian gerbils (Meriones unguiculatus) obtained from the Experimental Animal Center, Hallym University, Chunchon, South Korea. The animals were housed at constant temperature (23 °C) and relative humidity (60%) with a fixed 12 h light/12 h dark cycle and free access to food and water. Procedures involving animals and their care were conformed to the institutional guidelines, which are in compliance with current international laws and policies (NIH Guide for the
Delayed neuronal death in the CA1 region
In the present study, we confirmed delayed neuronal death in the hippocampal CA1 region using NeuN immunohistochemistry. In the sham-operated group, neurons in hippocampal subfields were well-stained with NeuN antibody (Fig. 1A and B). One and 2 days after ischemic insult, there were no significant changes in NeuN immunoreactivity in CA1 pyramidal cells (Fig. 1C–F). We confirmed the delayed neuronal death in CA1 pyramidal cells 4 days following 5 min of transient forebrain ischemia. There was a
Discussion
In the present study, we confirmed delayed neuronal death in the gerbil hippocampal CA1 region 4 days after 5 min of transient forebrain ischemia using NeuN immunohistochemistry. Kirino (1982) had reported that the pyramidal cells of the hippocampal CA1 region showed delayed neuronal death 4 days after 5 min of transient forebrain ischemia in gerbils. However, the pattern of delayed neuronal death was controversial. In recent studies, the delayed neuronal death was intermingled with apoptosis and
Acknowledgements
The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee and Ms. Hyun Sook Kim for their technical help for this study. This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A020007).
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