Differential activation of ER stress pathways in myelinating cerebellar tracts.

摘要: Myelin production during brain development requires an increase in membrane protein and lipid oligodendrocytes this primarily occurs the endoplasmic reticulum (ER), organelle which initiates Unfolded Protein Response (UPR) when under stress. We hypothesise that UPR is activated white matter tracts myelination order to expand ER capacity of oligodendrocytes. Using early late stage markers, critical time points were identified by immunohistochemistry developing rat cerebellum. These correlated peaks stress signalling staining for transducers (pIRE1, ATF6 pPERK) associated downstream molecules (peIF2α, PDI, GRP78, GRP94, CHOP calreticulin) cerebellar III IV. Gene expression cerebellum was assessed qPCR. Actively myelinating shown have differential pIRE1, PERK as well targets GRP78 PDI. Activated pIRE1-positive cells widespread at P14 P17 significantly higher numbers than other stages. Nuclear-localised (indicative active transcription factor) peaked P10, concurrent with initial phase myelination. The percentage positive pPERK less 1% postnatal ages but increased adult tissue. GRP94 PDI up-regulated compared P7 remained elevated adults. majority these markers confirmed dual-labelling. Although gene did not change over time, XBP1s both showed significant fold changes between timepoints. This data helps promote understanding events occurring developmental may implications reparative treatments diseases such multiple sclerosis.