Could Parkinson disease (PD) be an autoimmune disease linked to gastrointestinal infections that happen years before onset of the neurological disorder? According to a study published Wednesday in the journal Nature, a gut infection in mice lacking a gene linked to PD led to similar symptoms.
The researchers said the study suggests the possibility of an earlier window of time for possible interventions and treatment strategies for some forms of PD.
PD is marked by a significant loss of dopamine neurons in a section of the brain called the substantia nigra pars compacta. While the exact mechanisms that trigger this loss are unclear, mitochondrial dysfunction and inflammation are thought to play key roles.
An early-onset form of PD is linked with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes, accounting for about 10% of PD cases. However, in mouse models, the same mutations do not generate disease symptoms, leading many researchers to conclude that mice may not be suitable for the study of PD. But researchers from Montreal think that findings in this new study may explain why these mouse models may not show PD symptoms: unlike humans, these animals are normally kept in germ-free facilities.
In this study, young mice lacking a gene linked to PD were infected with Gram-negative bacteria, which triggered PD-like symptoms later in life. The PD-like symptoms could be temporarily reversed by the administration of levodopa, a drug used to treat Parkinson.
In a statement, the researchers said that in normal mice, the immune system responded properly to the gut infection. But in mice lacking PINK1, the immune system overreacted and triggered autoimmunity, suggesting that rather than dying from toxin accumulation, the killing of dopaminergic neurons involves immune cells. In the infected mutant mice, autoreactive toxic T lymphocytes were shown to be present in the brain and able to attack healthy neurons in culture dishes.
"These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson’s disease, highlighting the relevance of the gut—brain axis in the disease," the researchers wrote.
A joint team of scientists from the Université de Montréal, the Montreal Neurological Institute, and McGill University conducted the study.