AUTHOR=Kitisin Thitinan , Muangkaew Watcharamat , Sukphopetch Passanesh 

TITLE=Infections of Cryptococcus species induce degeneration of dopaminergic neurons and accumulation of α-Synuclein in Caenorhabditis elegans

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1039336

DOI=10.3389/fcimb.2022.1039336

ISSN=2235-2988

ABSTRACT=<p>Cryptococcosis in the central nervous system (CNS) can present with motor declines described as Parkinsonism. Although several lines of evidence indicate that dopaminergic (DA) neuron degeneration and α-synuclein accumulation contribute to the hallmark of Parkinsonism and Parkinson’s disease (PD), little is known about cryptococcal infections associated with neuronal degeneration. In this study, the effects of <italic>Cryptococcus neoformans</italic> and <italic>C. gattii</italic> infections on dopaminergic neuron degeneration, α-synuclein accumulation, and lifespan in <italic>Caenorhabditis elegans</italic> were investigated. The results showed that cryptococcal infections significantly (<italic>P</italic>&lt;0.05) induced DA neuron degeneration similar to a selective cathecholamine neurotoxin 6-hydroxydopamine (6-OHDA) in <italic>C. elegans</italic> (BZ555 strain) when compared to mock infected controls. Cryptococcal infections also significantly (<italic>P</italic>&lt; 0.05) induced α-synuclein aggregation in <italic>C. elegans</italic> (NL5901 strain). Moreover, lifespan of the infected worms was significantly decreased (<italic>P</italic>&lt;0.0001). In conclusion, DA neurodegeneration and α-synuclein accumulation are associated with lifespan reduction during cryptococcal infection in <italic>C elegans</italic>.</p>