
Contributions
Abstract: EP1465
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Heat shock protein (HSP) are conservative proteins involved in proper protein folding, stress-induced cell responses, facilitating autoimmune response and neuroprotection. The role of HSP, which are overexpressed in demyelinating lesion in MS brain, is unknown .
To examine HSP function in autoimmune (experimental autoimmune encephalomyelitis- EAE model) and toxic (lysolecithine- LL injury) demyelination we produce transgenic mice with HSP70 overexpression specifically in astrocytes (GFAP/hsp70Tg) or oligodendrocytes (MBP/hsp70Tg). The MBP/hsp70Tg and GFAP/hsp70Tg mice were sensitized for EAE with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 and EAE was clinically scored to 1-5 grade scale. The remyelination processes were assessed after toxic demyelination induced by injection of LL into thoracic spinal cord. The remyelination in LL model of demyelination was assessed with toluidin blue staining.
The MBP/hsp70Tg mice showed enhance EAE symptoms in compare to control mice (2,5 v. 1,5, respectively). In LL model of demyelination enhanced damage of tissue and almost complete lack of remyelination was observed in MBP/hsp70Tg mice in compare to control mice (remyelination rank: 2,5 v. 7,8, respectively). These data suggest that hsp70 overexpression did not prevent oligodendrocyte demise but enhance inflammatory responses. Confirming this hypothesis was the observation that oligodendrocytes isolated from MBP/hsp70Tg mice were not resistant to TNF-induced death and lymphocytes isolated from EAE MBP/hsp70Tg mice showed enhance response to myelin antigen in compare to control mice (SI: 5,6 v. 2,2). In GFAP/hsp70Tg mice EAE symptoms were milder in compare to control mice (0,8 v. 1,5, respectively). The lymphocyte proliferation in response to myelin antigens were similar in GFAP/hsp70Tg and control mice. However the remyelination in GFAP/hsp70Tg mice after LL injection was slightly inhibited in compare to control mice as assessed by remyelination rank (6,1 v. 7,8, respectively).The hsp70 overexpression in oligodendrocytes did not change oligodendrocytes resistance to inflammatory-induced death but enhanced EAE symptoms and inflammatory responses. The hsp70 overexpression in astrocyte have protective effect on EAE course however do not enhance remyelination.
Disclosure: A. Jurewicz nothing to disclose
G. Galazka nothing to disclose
M. Zawadzka nothing to disclose
M. Domowicz nothing to disclose
G. Kollias nothing to disclose
K. Selmaj nothing to disclose
Abstract: EP1465
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Heat shock protein (HSP) are conservative proteins involved in proper protein folding, stress-induced cell responses, facilitating autoimmune response and neuroprotection. The role of HSP, which are overexpressed in demyelinating lesion in MS brain, is unknown .
To examine HSP function in autoimmune (experimental autoimmune encephalomyelitis- EAE model) and toxic (lysolecithine- LL injury) demyelination we produce transgenic mice with HSP70 overexpression specifically in astrocytes (GFAP/hsp70Tg) or oligodendrocytes (MBP/hsp70Tg). The MBP/hsp70Tg and GFAP/hsp70Tg mice were sensitized for EAE with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 and EAE was clinically scored to 1-5 grade scale. The remyelination processes were assessed after toxic demyelination induced by injection of LL into thoracic spinal cord. The remyelination in LL model of demyelination was assessed with toluidin blue staining.
The MBP/hsp70Tg mice showed enhance EAE symptoms in compare to control mice (2,5 v. 1,5, respectively). In LL model of demyelination enhanced damage of tissue and almost complete lack of remyelination was observed in MBP/hsp70Tg mice in compare to control mice (remyelination rank: 2,5 v. 7,8, respectively). These data suggest that hsp70 overexpression did not prevent oligodendrocyte demise but enhance inflammatory responses. Confirming this hypothesis was the observation that oligodendrocytes isolated from MBP/hsp70Tg mice were not resistant to TNF-induced death and lymphocytes isolated from EAE MBP/hsp70Tg mice showed enhance response to myelin antigen in compare to control mice (SI: 5,6 v. 2,2). In GFAP/hsp70Tg mice EAE symptoms were milder in compare to control mice (0,8 v. 1,5, respectively). The lymphocyte proliferation in response to myelin antigens were similar in GFAP/hsp70Tg and control mice. However the remyelination in GFAP/hsp70Tg mice after LL injection was slightly inhibited in compare to control mice as assessed by remyelination rank (6,1 v. 7,8, respectively).The hsp70 overexpression in oligodendrocytes did not change oligodendrocytes resistance to inflammatory-induced death but enhanced EAE symptoms and inflammatory responses. The hsp70 overexpression in astrocyte have protective effect on EAE course however do not enhance remyelination.
Disclosure: A. Jurewicz nothing to disclose
G. Galazka nothing to disclose
M. Zawadzka nothing to disclose
M. Domowicz nothing to disclose
G. Kollias nothing to disclose
K. Selmaj nothing to disclose