engleski

Hippocampal expression of cytokines, metallothionein I/II and glycoprotein 96 in animal models of multiple sclerosis: Impact on adult neurogenesis

Background/Objectives: Inflammatory, demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are often followed by cognitive deficits associated with the neuronal injury, synaptic loss and altered neurogenesis within the hippocampus. Changes depend on the genetic and epigenetic factors that ensure the cellular and environmental homeostasis and regulate the interactions among immunocompetent, glial and neural cells. Owing to known participation of cytokines and stress proteins in maintenance of this balance, in this study we compared the expression profile of IL-6, TGF-b, metallothionein I/II (MTs) and glycoprotein 96 in the hippocampus of DA and AO rats that differ in the susceptibility to the induction of EAE and estimated the relationship of gp96 and MTs to adult neurogenesis occurring in subgranular zone (SGZ) of hippocampus. Design/Method: EAE was induced by immunization of rats by bovine brain homogenate emulsified in complete Freund's adjuvant. Results have shown that first attack of disease in DA rats was followed by upregulation of IL-6, TGF-b and MTs, reduced cellularity of granule cell layer, lower expression of gp96/granule cell, greater apoptosis and astrogliosis and elevated number of microglial and new neural cells expressing MT I/II and gp96. In SGZ the signs of an aberrant differentiation of neural precursors to doublecortin positive neuroblasts were found. Conclusions: The data show that inflammation, increased apoptosis and reduced or delayed hippocampal neurogenesis might contributed to the development of hippocampal dysfunction in chronic autoimmune CNS diseases, as well as that MT I/II and endoplasmic reticulum resident chaperons participate in the reestablishment of hippocampal integrity

Hippocampus ; metallothioneins ; gp96 ; neurogenesis

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