Contributions
Abstract: P954
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background: Two neuronal sites are important for action potential generation and propagation: the grey matter axon initial segment (AIS) and the white matter node of Ranvier (NOR). The AIS is the proximal part of the axon, which is not covered by a myelin sheath and possesses a distinctive, specialized assembly of voltage-gated ion channels and associated proteins. The nodes of Ranvier are periodic gaps in the insulating myelin sheaths of myelinated axons, are highly enriched in ion channels, allowing them to participate in the exchange of ions required to regenerate the action potential. Both, AIS and NOR pathology might contribute to disturbed neuronal functioning.
Objectives: In this study, we aim to discover structural changes at the AIS and the node of Ranvier during innate and adaptive immunity.
Methods: T-cell dependent (MOG35-55-induced experimental autoimmune encephalomyelitis (EAE)) as well as T-cell independent demyelination models (cuprizone-induced demyelination) have been included. Using anti-ankyrinG and anti-beta-IV-spectrin immunohistochemistry, we characterized the number and length of AIS and nodes of Ranvier.
Results: The pure activation of innate immunity (i.e. cuprizone intoxication) within the brain resulted in an early and dramatic reduction of ankyrinG staining at NOR sites. Of note, node of Ranvier pathology occurred prior to demyelination or axonal damage (i.e. at week 1). Later, at week 5, axon initial segment length was found to be increased. In contrast to our observation in the cuprizone model, brain AIS length was decreased in MOG35-55-induced EAE.
Conclusion: Our results suggest that impairment of the morphological node of Ranvier organization is an early event during cuprizone-induced demyelination and might be a potent trigger for subsequent axonal damage and demyelination. Furthermore, cortical demyelination might impact on morphological AIS organization and in consequence the generation of action potential. Both mechanisms might contribute to a disturbed neuronal signal processing.
Disclosure:
Carolin Ertl: nothing to disclose
Maren Engelhardt: nothing to disclose
Nora Jamann: nothing to disclose
Markus Kipp: nothing to disclose
Abstract: P954
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background: Two neuronal sites are important for action potential generation and propagation: the grey matter axon initial segment (AIS) and the white matter node of Ranvier (NOR). The AIS is the proximal part of the axon, which is not covered by a myelin sheath and possesses a distinctive, specialized assembly of voltage-gated ion channels and associated proteins. The nodes of Ranvier are periodic gaps in the insulating myelin sheaths of myelinated axons, are highly enriched in ion channels, allowing them to participate in the exchange of ions required to regenerate the action potential. Both, AIS and NOR pathology might contribute to disturbed neuronal functioning.
Objectives: In this study, we aim to discover structural changes at the AIS and the node of Ranvier during innate and adaptive immunity.
Methods: T-cell dependent (MOG35-55-induced experimental autoimmune encephalomyelitis (EAE)) as well as T-cell independent demyelination models (cuprizone-induced demyelination) have been included. Using anti-ankyrinG and anti-beta-IV-spectrin immunohistochemistry, we characterized the number and length of AIS and nodes of Ranvier.
Results: The pure activation of innate immunity (i.e. cuprizone intoxication) within the brain resulted in an early and dramatic reduction of ankyrinG staining at NOR sites. Of note, node of Ranvier pathology occurred prior to demyelination or axonal damage (i.e. at week 1). Later, at week 5, axon initial segment length was found to be increased. In contrast to our observation in the cuprizone model, brain AIS length was decreased in MOG35-55-induced EAE.
Conclusion: Our results suggest that impairment of the morphological node of Ranvier organization is an early event during cuprizone-induced demyelination and might be a potent trigger for subsequent axonal damage and demyelination. Furthermore, cortical demyelination might impact on morphological AIS organization and in consequence the generation of action potential. Both mechanisms might contribute to a disturbed neuronal signal processing.
Disclosure:
Carolin Ertl: nothing to disclose
Maren Engelhardt: nothing to disclose
Nora Jamann: nothing to disclose
Markus Kipp: nothing to disclose