Contributions
Abstract: P400
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Axonal damage has been identified as a significant contributor of permanent clinical disability in multiple sclerosis. In the context of demyelinating disorders, this destructive event could be the result of inflammation, demyelination and/or the activation of innate defense cells such as microglia or monocytes. The relative contribution of each of these variables to acute axonal injury is, however, unknown.
In the present study, we compared the extent of acute axonal damage in three different murine demyelination models using anti-amyloid precursor protein (APP) immunohistochemistry. T-cell dependent (MOG35-55-induced experimental autoimmune encephalomyelitis (EAE)) as well as T-cell independent demyelination models (cuprizone- and lysolecithin-induced demyelination) have been included.
APP-positive spheroids were present in all three experimental demyelination models. The number of APP-positive spheroids was greatest within lysolecithin-induced lesions. Equal amounts were found in the spinal cord of EAE animals and the corpus callosum of cuprizone-intoxicated animals. Moreover, we detected increased immunoreactivity of another pre-synaptic protein, i.e. vesicular glutamate transporter 1 (VGlut1) in demyelinated foci. VGlut1-staining revealed long stretched, ovoid-like structures, which colocalized with APP.
In summary, we were able to show that acute axonal damage is evident under various experimental demyelination paradigms. Furthermore, disturbed axonal transport, which is responsible for intra-axonal APP-accumulation, is not only restricted to APP but also to other synaptic proteins. These results indicate that despite differences in their characteristics, all three models may serve as a good model for investigating responsible mechanisms of axonal damage and potential protective strategies.
Disclosure:
Tanja Hochstrasser: nothing to disclose
Katharina Marie Höflich: nothing to disclose
Markus Kipp: nothing to disclose
This research project was supported by the Doktor Robert Pfleger - Foundation.
Abstract: P400
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Axonal damage has been identified as a significant contributor of permanent clinical disability in multiple sclerosis. In the context of demyelinating disorders, this destructive event could be the result of inflammation, demyelination and/or the activation of innate defense cells such as microglia or monocytes. The relative contribution of each of these variables to acute axonal injury is, however, unknown.
In the present study, we compared the extent of acute axonal damage in three different murine demyelination models using anti-amyloid precursor protein (APP) immunohistochemistry. T-cell dependent (MOG35-55-induced experimental autoimmune encephalomyelitis (EAE)) as well as T-cell independent demyelination models (cuprizone- and lysolecithin-induced demyelination) have been included.
APP-positive spheroids were present in all three experimental demyelination models. The number of APP-positive spheroids was greatest within lysolecithin-induced lesions. Equal amounts were found in the spinal cord of EAE animals and the corpus callosum of cuprizone-intoxicated animals. Moreover, we detected increased immunoreactivity of another pre-synaptic protein, i.e. vesicular glutamate transporter 1 (VGlut1) in demyelinated foci. VGlut1-staining revealed long stretched, ovoid-like structures, which colocalized with APP.
In summary, we were able to show that acute axonal damage is evident under various experimental demyelination paradigms. Furthermore, disturbed axonal transport, which is responsible for intra-axonal APP-accumulation, is not only restricted to APP but also to other synaptic proteins. These results indicate that despite differences in their characteristics, all three models may serve as a good model for investigating responsible mechanisms of axonal damage and potential protective strategies.
Disclosure:
Tanja Hochstrasser: nothing to disclose
Katharina Marie Höflich: nothing to disclose
Markus Kipp: nothing to disclose
This research project was supported by the Doktor Robert Pfleger - Foundation.