| Popis: |
Endoplasmic reticulum (ER) stress is a homeostatic signalling pathway, linked to many neurological diseases including multiple sclerosis (MS), which can lead to cell death when prolonged. Increasing evidence suggests that Calreticulin (CRT), a multifunctional ER resident chaperone protein, plays a role in apoptotic cell clearance and it is implicated in autoimmunity. Studies in human tissue, in our lab, have shown ER stress-associated molecules at increased levels, in white and grey matter MS lesions. To complement this work we have set up EAE animal models of inflammatory white and grey matter lesions in female Dark Agouti (DA) rats and report here the profile of expression of ER stress signalling molecules in lesioned tissue. White matter demyelination was induced in rats by immunisation with 25-50 µg of recombinant myelin oligodendrocyte glycoprotein (rmMOG) emulsified in incomplete Freund's adjuvant (IFA) and control rats were injected with IFA or saline alone. EAE spinal cord white matter lesions were present in the dorsal, ventral and lateral funiculi. Cortical demyelinated lesions were produced by immunising DA rats with a sub-clinical dose of rmMOG (5 µg) to prime animals and then 21 days later proinflammatory TNFalpha and IFN gamma were stereotactically injected into the subarachnoid space. Semiquantitative analysis of immunostained tissue revealed CHOP (p |
