Background: Parkinson's disease (PD) is intricately linked to gastrointestinal inflammation and the presence of neurotoxins in the gut, integrating α-syn pathologic alterations and subsequent neurodegeneration into the brain. Objectives: This study aimed to explore the enduring impact of dextran sodium sulfate (DSS)-mediated colitis on the vulnerability of central dopaminergic neurons to subsequent rotenone exposure. Methods: To induce chronic colitis, 10-month-old C57BL/6 mice were pre-exposed to 3 cycles of 1 week of 1% (w/v) DSS administration in drinking water followed by 2 weeks of regular drinking water. After colitis induction, animals received a low dose of intragastric rotenone for the next 8 weeks, followed by testing for Parkinsonian behavior and GI phenotypes of inflammation. At the end of the 17th week, colon, brain stem, and midbrain tissue were isolated and analyzed for α-syn, inflammatory markers, and dopaminergic neuronal loss. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Results: We found that chronic rotenone administration in the presence of preexisting colitis led to a further increase in colonic pro-inflammatory mediator expressions, α-syn expression, and reduced colonic tight junction protein expressions. We also found early impairment of GI functions and worsened grip strength in rotenone-exposed colitic mice. Furthermore, α-syn pathology specific to the colitic mice exposed to rotenone showed dopaminergic neurons degeneration and astroglial activation in substantia nigra and striatum, including regions of the brain stem, i.e., dorsal motor of the vagus and locus coeruleus. Finally, the result of 16S rRNA gene sequencing analysis indicated that colitic mice, after being exposed to rotenone, exhibited a discernible trend in their microbiota composition (Catenibacterium, Turicibactor, and clostridium sensue stricto 1), linking it to the development of PD. Conclusions: These findings indicate that prolonged low-dose rotenone exposure, combined with an early inflammatory intestinal milieu, provides a preconditioning effect on α-syn pathology and exerts neurodegeneration in the intragastric rotenone PD mouse model.

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Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which was identified in Wuhan, China in December 2019 and jeopardized human lives. It spreads at an unprecedented rate worldwide, with serious and still-unfolding health conditions and economic ramifications. Based on the clinical investigations, the severity of COVID-19 appears to be highly variable, ranging from mild to severe infections including the death of an infected individual. To add to this, patients with comorbid conditions such as age or concomitant illnesses are significant predictors of the disease's severity and progression. SARS-CoV-2 enters inside the host cells through ACE2 (angiotensin converting enzyme2) receptor expression; therefore, comorbidities associated with higher ACE2 expression may enhance the virus entry and the severity of COVID-19 infection. It has already been recognized that age-related comorbidities such as Parkinson's disease, cancer, diabetes, and cardiovascular diseases may lead to life-threatening illnesses in COVID-19-infected patients. COVID-19 infection results in the excessive release of cytokines, called "cytokine storm", which causes the worsening of comorbid disease conditions. Different mechanisms of COVID-19 infections leading to intensive care unit (ICU) admissions or deaths have been hypothesized. This review provides insights into the relationship between various comorbidities and COVID-19 infection. We further discuss the potential pathophysiological correlation between COVID-19 disease and comorbidities with the medical interventions for comorbid patients. Toward the end, different therapeutic options have been discussed for COVID-19-infected comorbid patients.

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