NeuralCipher Research overview
The text below is the source article’s original abstract under a verified reuse license. cc by
ABSTRACT Background Influenza virus exposure elevates the incidence of parkinsonism. We and others previously discovered that allelic variants at the Parkinson’s-linked LRRK2 locus modulate host responses to virulent microbes. Objective We asked whether Lrrk2 mutations modify disease outcomes in adult animals following a nasally acquired lung infection. Methods We inoculated C57BL/6J mice of mutant knock-in Lrrk2 genotypes with influenza A virus, H1N1-serotype (1 x LD 50 = 2,000 plaque-forming units). Results During H1N1-induced pneumonitis neither homozygous nor heterozygous mutations of kinase activity-increasing Lrrk2 G2019S or kinase-dead Lrrk2 D1994S altered the course of sickness in mice when compared to wild-type littermates, as determined by survival rates, viral titres and weight changes in both sexes. However, six weeks after inoculation brains of H1N1-exposed, homozygous Lrrk2 p.G2019S animals showed higher pSer 129 α-synuclein and pSer 199 tau levels than mock-treated, mutant mice ( PConclusion Homozygous Lrrk2 G2019S -mutant mice that survived infection by a life-threatening, pneumotropic RNA virus show changes in brain levels of oxidative stress, pSer 199 tau and pSer 129 α-synuclein. These results could be of relevance to the initiation of neurodegeneration-linked changes in humans and may help explain differences in the penetrance rate and expressivity of LRRK2 mutants.
Scientific assessment
Research question
Assess the question within the original study’s scope.
Methods & sample
Check the source article for study design and sample details.
Key findings
An editorially approved findings summary is not yet published for this record.
Limitations
Generalizability, bias and clinical meaning require separate assessment.
Methods, samples and clinical conclusions are not inferred from bibliographic metadata.