School of Medicine and Health Sciences Poster Presentations
Early oligodendrocyte ablation alters CNS responses to immune mediated demyelination in the adult mouse.
Poster Number
122
Document Type
Poster
Status
Staff
Abstract Category
Basic Biomedical Sciences
Keywords
Demyelination, Multiple Sclerosis, Experimental Autoimmune encephalomyelitis, ligodendrocyte, oligodendrocyte progenitor cell
Publication Date
Spring 2018
Abstract
Experimental autoimmune encephalomyelitis (EAE) is the most common experimental model for multiple sclerosis, an autoimmune mediated neurodegenerative disease characterized by oligodendrocyte (OL) apoptosis, demyelination, and inflammation within the central nervous system. OLs are responsible for myelination in the central nervous system and their ablation results in demyelination. Remyelination occurs relatively soon following early OL ablation due to the high number of oligodendrocyte progenitor cells (OPCs) in early life. OL ablation was achieved by injecting MPB-iCP9 transgenic mice, which express an inducible form of caspase 9 (icP9) driven by a fragment of the MBP promoter, with Chemical Inducer of Dimerization (CID). To induce the primary insult CID was delivered via intra-peritoneal injection to transgenic mice at postnatal day 4 over a 2 week period. Following remyelination, the second insult was introduced via EAE induction at 10-11 weeks of age. Mice were sacrificed 2 weeks post EAE induction and spinal cords harvested and fixed with PFA for histological examination. Demyelinating lesions were observed as patches of disrupted solochrome staining in spinal cord section preparations. Preliminary results show no significant difference in focal area of demyelination in spinal cord sections treated with EAE alone versus EAE preceded by CID. Immunohistological staining show relative increases in NG2 (OPC marker), CD45 (immune cell marker), Iba1 (microglia marker), and CD23 (mast cell marker) in spinal cord sections exposed to double insult compared to EAE alone. These results suggest an increase in both OPCs and an increase in inflammation in CID+ EAE versus EAE induction alone. Further studies will include examination of OPC proliferation in CID+EAE vs EAE by immunohistological staining with Ki67 and PDGFR markers.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Open Access
1
Early oligodendrocyte ablation alters CNS responses to immune mediated demyelination in the adult mouse.
Experimental autoimmune encephalomyelitis (EAE) is the most common experimental model for multiple sclerosis, an autoimmune mediated neurodegenerative disease characterized by oligodendrocyte (OL) apoptosis, demyelination, and inflammation within the central nervous system. OLs are responsible for myelination in the central nervous system and their ablation results in demyelination. Remyelination occurs relatively soon following early OL ablation due to the high number of oligodendrocyte progenitor cells (OPCs) in early life. OL ablation was achieved by injecting MPB-iCP9 transgenic mice, which express an inducible form of caspase 9 (icP9) driven by a fragment of the MBP promoter, with Chemical Inducer of Dimerization (CID). To induce the primary insult CID was delivered via intra-peritoneal injection to transgenic mice at postnatal day 4 over a 2 week period. Following remyelination, the second insult was introduced via EAE induction at 10-11 weeks of age. Mice were sacrificed 2 weeks post EAE induction and spinal cords harvested and fixed with PFA for histological examination. Demyelinating lesions were observed as patches of disrupted solochrome staining in spinal cord section preparations. Preliminary results show no significant difference in focal area of demyelination in spinal cord sections treated with EAE alone versus EAE preceded by CID. Immunohistological staining show relative increases in NG2 (OPC marker), CD45 (immune cell marker), Iba1 (microglia marker), and CD23 (mast cell marker) in spinal cord sections exposed to double insult compared to EAE alone. These results suggest an increase in both OPCs and an increase in inflammation in CID+ EAE versus EAE induction alone. Further studies will include examination of OPC proliferation in CID+EAE vs EAE by immunohistological staining with Ki67 and PDGFR markers.