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Hippocampal expression of heat shock protein GP 96, CD91 and TLR2 during experimental autoimmune encephalomyelitis in rats

Introduction. Demyelinating autoimmune diseases, such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are often followed by cognitive deficits associated with the inflammation, neuronal injury and altered neurogenesis within the hippocampus. Pathogenic mechanisms include the appearance of "danger signals" that contribute to neuronal dyshomeostasis and activation o f innate and adaptive immunity, as well as those that provide neuroprotection and ensure the restoration of tolerance. Aim. To estimate the expression profiles of endoplasmic reticulum (ER)-resident chaperon gp96 and its receptors - CD91 and Toll- like receptor 2 (TLR2) in hippocampi of DA rats during the course of EAE, since these pathways are involved in unfolded protein response (UPR) and F.R-associated degradation of the misfolded proteins, as well as in activation of immune response. Methods: Rats were immunized with BBH in complete Freund's adjuvant (CFA) or only with CFA. The expressions of gp96, CD91 and TLR2 were estimated on days 12 and 22 after immunization by PCR. Western blot and immunohistochemistry. Results: Granular cells constitutively expressed gp96. but its mRNA decreased in early phase of EAE and arose during remission of disease. CD9I and TLR2 genes expression increased in both phases of EAE. but protein expression of CD91 was greater in acute than in late phase of EAE. In contrast. TLR2 protein expression increased particularly in remission phase of EAE. Moreover, in late phase of EAE gp96 was co-localized with CD91 in granular neurons, as well as with TLR2 in numerous doublecortin positive neuroblasts in SGZ of dentate gyros Conclusions: The data point to time-dependent expression of gp96 during EAE and its receptors and imply that during an autoimmune reaction gp96 may through UPR and CD91 and TLR2 signaling affect the reestablishment of hippocampal integrity and adult neurogenesis.

adult neurogenesis, gp96, TLR2, experimental autoimmune encephalomyelitis

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