title: Long-term intrathecal infusion of outer surface protein C from Borrelia burgdorferi causes axonal damage.
abstract: Lyme neuroborreliosis (LNB) is the most frequent tick-borne infectious disease of the central nervous system. In acute LNB and the rare chronic state of infection, patients can experience cognitive deficits such as attention and memory disturbances. During LNB, single compounds of Borrelia burgdorferi sensu lato are released into the subarachnoid space.To investigate the pathogenesis of neurologic dysfunction in LNB, we determined that the outer surface protein C (OspC), a major virulence factor of B. burgdorferi, stimulated mouse microglial cells in a dose-dependent manner to release nitric oxide (EC50 = 0.24 mg/L) in vitro. To mimic pathophysiologic conditions of long-term release of this bacterial component in vivo, we treated C57BL/6 mice with recombinant OspC from Borrelia garinii or buffer by intraventricular infusion and tested them for behavioral deficits. After 4weeks, brains were examined by routine histology and immunohistochemistry. Assessment of spatial learning and memory of treated mice during OspC exposure did not reveal significant differences from controls. Continuous exposure to intrathecal B. burgdorferi OspC led to activation of microglia and axonal damage without demonstrable cognitive impairment in experimental mice. These results suggest that long-term intrathecal exposure to OspC resulted in axonal damage that may underlie the neurologic manifestations in chronic LNB.
authors.affiliation: Department of Neurology (SCT), RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.forename: Sandra
authors.initials: S
authors.lastname: Ebert
authors.forename: Torsten
authors.initials: T
authors.lastname: Heinz
authors.forename: Volker
authors.initials: V
authors.lastname: Fingerle
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bunkowski
authors.forename: Dominik
authors.initials: D
authors.lastname: Kugelstadt
authors.forename: Annette
authors.initials: A
authors.lastname: Spreer
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.forename: Helmut
authors.initials: H
authors.lastname: Eiffert
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000942:Antigens, Bacterial / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000187:drug effects*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage*; D025065:Borrelia burgdorferi / Q000737:chemistry; D001921:Brain / Q000166:cytology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D007278:Injections, Spinal / Q000379:methods; D008193:Lyme Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011134:Polysaccharides / Q000633:toxicity; D048069:Tumor Necrosis Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C491049:Aif1 protein, mouse; D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D002135:Calcium-Binding Proteins; D054382:Chemokine CXCL13; D008840:Microfilament Proteins; C079616:OspC protein; D011134:Polysaccharides; D048069:Tumor Necrosis Factors