Glial expression of the 90‐kDa heat shock protein (HSP90) and the 94‐kDa glucose‐regulated protein (GRP94) following an excitotoxic lesion in the mouse hippocampus

Abstract

Heat shock proteins (HSPs) are immediately expressed in neuronal and glial cells under various stressful conditions and play a protective role through molecular chaperones. Although several studies have been focused on the expression of HSPs, little is known about HSP90s expression in glial cells under neuropathological conditions. In this study, we evaluated the expression pattern of the glial cell-related HSP90 and GRP94 proteins, following the induction of an excitotoxic lesion in the mouse brain. Adult mice received an intracerebroventricular injection of kainic acid; the brain tissue was then analyzed immunohistochemically for HSPs and double labeling using glial markers. HSPs expression was quantified by Western blot analysis. Excitotoxic damage was found to cause pyramidal cell degeneration in the CA3 region of the hippocampus. In the injured hippocampus, reactive microglia/macrophages expressed HSP90 from 12 h until 7 days postlesion (PL), showing maximal levels at day 1. In parallel, hippocampal reactive astrocytes showed the expression of GRP94 from 12 h until 7 days PL. In general, HSPs expression was transient, peaked at 1-3 days PL and reached basal levels by day 7. For the first time, our data demonstrate the injury-induced expression of HSP90 and GRP94 in glial cells, which may contribute to the mechanism of glial cell protection and adaptation in response to damage, thereby playing an important role in the evolution of the glial response and the excitotoxic lesion outcome. HSP90 may provide antioxidant protective mechanisms against microglia/macrophages, whereas GRP94 may stabilize the astroglial cytoskeleton and participate in astroglial antioxidant mechanisms.

Expression of l-Serine Biosynthetic Enzyme 3-Phosphoglycerate Dehydrogenase (Phgdh) and Neutral Amino Acid Transporter ASCT1 Following an Excitotoxic Lesion in the Mouse Hippocampus

“…A selective lesion in the CA3 of the hippocampal region of the KA-injected mouse was revealed (data not shown), as we described previously [12]. The pyramidal cell degeneration in the CA3 region appeared at 1 day post-KA injection.…”

“…Brains were removed, postfixed for 4 h, and cryoprotected in cold 30% sucrose solution. Immunohistochemistry was performed using a previously described free-floating method [12]. Rabbit anti-Phgdh (1:600; Yamasaki et al [32], generously provided by Dr. Masahiko Watanabe, Hokkaido University School of Medicine, Japan) and rabbit anti-ASCT1 (Chemicon, Temecula, CA) were used as primary antibodies at a 1:200 dilution.…”

Selenoprotein S expression in reactive astrocytes following brain injury

“…In fact, they synthesize and release large amounts of molecules, forcing an incremented protein trafficking through the ER. In agreement with this notion, intracerebroventricular injection of KA increases the expression of the ERchaperone grp94 specifically in reactive astrocytes (Jeon et al, 2004). OASIS and BIP were also found increased in reactive astrocytes in KA-induced injury (Chihara et al, 2009).…”

“…However, in agreement with our results, there are other evidence indicating that ER responses are different in astrocytes and microglia. Thus, in a previous work that also used KA toxicity as a model of gliosis, the ER chaperone grp94 was induced specifically in astrocytes (Jeon et al, 2004). Fig.…”

EXPOSURE TO 2.45 GHz MICROWAVE RADIATION PROVOKES CEREBRAL CHANGES IN INDUCTION OF HSP-90 α/β HEAT SHOCK PROTEIN IN RAT.

“…Other stress-related stimuli such as fever, convulsions [20], drugs (amphetamine or LSD) [21], injury and neurodegenerative diseases [22] cause modifications in the basal levels of HSP-90. An increase in HSP-90 in neuronal subpopulations [23] and/or its activation in new non neuronal glial and microglial cell populations [24] indicates participation by this protein in neuroprotective mechanisms [25], oxidative stress [26] and anti-apoptic activity [27,28].…”