Naslov
Hippocampal expression of metallothioneins I+II, gp96 and cytokines in rat strains with different susceptibility to experimental autoimmune encephalomyelitis

Autori
Grubić-Kezele, Tanja ; Blagojević Zagorac, Gordana ; Jakovac, Hrvoje ; Domitrović, Robert ; Radošević-Stašić, Biserka.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book / Polić, Bojan - Rijeka : The Croatian Immunological Society, 2014, 63-63

Skup
Godišnji skup Hrvatskog imunološkog društva

Mjesto i datum
Krk, Hrvatska, 17.10.2014. - 18.10.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
EAE; hippocampus; metallothioneins; gp96; IL-6; Tgf beta; NFkappaB

Sažetak
Background: Inflammatory demyelinating diseases, such as MS and experimental autoimmune encephalomyelitis (EAE) are often followed by cognitive deficits associated with the neuronal injury and synaptic loss within the hippocampal CA1 pyramidal layer and an altered neurogenesis in the subgranular zone (SGZ) in the dentate gyrus (DG). Changes have been related with an imbalance in cellular and environmental homeostasis that is normally created by the continuous interaction of immune competent cells, glial cells and resident neural cells. Since, in the maintenance of CNS homeostasis participate metallothioneins (MTs) and heat shock proteins (HSPs), which protect the neurons from metal, free radical, cytokine-induced and proteotoxic injuries and contribute to the repair of neural tissues, in this study we analyzed the expression of MTs and endoplasmic reticulum (ER) resident HSP-gp96 in the hippocampus of Dark Agouti (DA) and Albino Oxford (AO) rats that differ in the susceptibility to induction of EAE. Methods: AO and DA rats were immunized with bovine brain homogenate (BBH) emulsified in complete Freund adjuvant (CFA) or only with CFA. The expression patterns of hippocampal MT I+II proteins, gp96, IL-6, NF-B and transforming growth factor (TGF)-ß were estimated on day 12 after immunization (when EAE-prone DA rats develop first attack of clinical symptoms), as well as in intact AO and DA rats, by immunohistochemistry, cell-based staining quantification with Cell F v3.1 software and by Western blot analysis in the lysates of the whole hippocampal tissue. Differences between groups were assessed by Mann-Whitney U test. Results: The data showed the hippocampal content of induced MTs, Il-6 and TGF-ß proteins was significantly greater in EAE-prone DA rats than in EAE-resistant AO rats, but that AO rats had greater constitutive expression of these proteins in intact hippocampus. Immunohistochemical data revealed that these changes were distributed mostly in the SGZ in DG, as well as that in DA rats immunized with encephalitogen increased also the nuclear expression of NF-B in some granule cells and the cytoplasmic expression of TGF-ß on some cells in the hilus. Furthermore, the data obtained by immunohistochemistry suggested that the expression of gp96 in granular layer of DA rats was downregulated in comparison with AO rats, but the total protein content of gp96 in the whole hippocampal tissue was not significantly different. Conclusions: The data show that autoimmune attack during EAE is followed by marked changes in the expressions MTs, ER-resident HSPs, IL-6 and TGF-ß in the hippocampal regions responsible for the adult neurogenesis, suggesting also that the interplay of these factors contribute to the different susceptibility of DA and AO rats to the induction of EAE.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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