Synaptophysin Is a Reliable Marker for Axonal Damage.
Synaptophysin is an abundant membrane protein of synaptic vesicles. The objective of this study was to determine the utility of identifying synaptophysin accumulations (spheroids/ovoids/bulbs) in CNS white matter as an immunohistochemical marker of axonal damage in demyelinating and neuroinflammatory conditions. We studied the cuprizone toxicity and Theiler’s murine encephalomyelitis virus (TMEV) infection models of demyelination and analyzed CNS tissue from patients with multiple sclerosis (MS). Synaptophysin colocalized with the amyloid precursor protein (APP), a well-known marker of axonal damage. In the cuprizone model, numerous pathological synaptophysin/APP-positive spheroids/ovoids were identified in the corpus callosum at the onset of demyelination; the extent of synaptophysin/APP-positive vesicle aggregates correlated with identified reactive microglia; during late and chronic demyelination, the majority of synaptophysin/APP-positive spheroids/ovoids resolved but a few remained, indicating persistent axonal damage; in the remyelination phase, scattered large synaptophysin/APP-positive bulbs persisted. In the TMEV model, only a few large- to medium-sized synaptophysin/APP-positive bulbs were found in demyelinated areas. In MS patient tissue samples, the bulbs appeared exclusively at the inflammatory edges of lesions. In conclusion, our data suggest that synaptophysin as a reliable marker of axonal damage in the CNS in inflammatory/demyelinating conditions.
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
Viktoria
V
Gudi
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
Lijie
L
Gai
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
Vanessa
V
Herder
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
Laura Salinas
LS
Tejedor
Department of Anatomy II, Ludwig-Maximilians-University of Munich, Munich, Germany.
Markus
M
Kipp
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Sandra
S
Amor
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
Kurt-Wolfram
KW
Sühs
Center for Systems Neuroscience, Hannover, Germany.|Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Florian
F
Hansmann
Center for Systems Neuroscience, Hannover, Germany.|Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Andreas
A
Beineke
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
Wolfgang
W
Baumgärtner
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
Martin
M
Stangel
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
Thomas
T
Skripuletz
Axonal damage; Demyelination; Inflammation; Synaptophysin