immunohistochemical-analysis-rat-central-nervous-system-peripheral

Immunohistochemical Analysis in the Rat Central Nervous System and Peripheral Lymph Node Tissue Sections

Immunohistochemistry (IHC) provides highly specific, reliable and attractive protein visualization. Correct performance and interpretation of an IHC-based ...

Medical University of Vienna

Studies dealing with transport of proteins from the oligodendrocyte cell body to the myelin sheath reveal the presence of different transport pathways. Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER) and then processed through the Golgi apparatus and transported to the myelin membranes. Myelin basic protein (MBP) on the other hand is synthesized locally at the ends of cell processes where its messenger RNA is translated on free ribosomes. Here we show that in rats that overexpress PLP, impairment of PLP transport from the cell body to the processes interferes with the translocation of other membrane proteins such as myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG), but not with peripherally translated MBP. In addition, it also impedes the transport of non-myelin proteins, for example the amyloid precursor protein (APP). At the ultrastructural level, the ER of these metabolically disturbed oligodendrocytes revealed extreme swelling of the cisternae, and immunohistochemistry revealed intense expression of the ER chaperone molecule BiP/GRP78 and ER folding enzyme protein disulfide isomerase (PDI). These features suggest that these oligodendrocytes, which were found exclusively in gray matter areas of the spinal cord, started an unfolded protein response while suffering from ER stress. Some of these disturbed oligodendrocytes were seen to undergo programmed cell death. These results indicate that gray matter oligodendrocyte differ from white matter oligodendrocytes in their capacity to stabilize metabolic disturbances by an unfolded protein response.

Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Immunological studies suggest that it is a T-cell mediated autoimmune disease, although an MS-specific target antigen for autoimmunity has so far not been identified. Models of experimental autoimmune encephalomyelitis in part reproduce features of MS, but none of the models so far covers the entire spectrum of pathology and immunology. Autoimmune disease of the nervous system has occasionally been observed in humans after active sensitization with brain tissue or brain cells, giving rise to acute demyelinating polyradiculoneuritis, acute disseminated encephalomyelitis and in rare cases reflecting an inflammatory demyelinating condition similar to acute multiple sclerosis. In this study we analyzed in detail the immunopathology in archival autopsy tissue of a patient who died with an MS like disease after repeated exposure to subcutaneous injections of lyophilized brain cells.

Article	Year
Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes. Journal of neuropathology and experimental neurology\| PubMed ID: 11829340	2002
Autoimmune encephalitis in humans: how closely does it reflect multiple sclerosis ? Acta neuropathologica communications\| PubMed ID: 26637427	2015

Marianne Leisser

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