MPTP-Treated Zebrafish Recapitulate ‘Late-Stage’ Parkinson’s-like Cognitive Decline

The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-µg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The experiments were implemented using the equipment and unique scientific installation “Biological collection–Genetic biomodels of neuropsychiatric disorders” (No. 493387) of the Federal State Budgetary Scientific Institution “Scientific Research Institute of Neurosciences and Medicine” theme no. AAAA-A21-121011990039-2 (2021–2025). The study partially used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684)

Apoptosis and apoptotic extracellular vesicular particles in atherogenesis

The review summarizes current notions on the role of apoptosis and apoptotic cell-derived extracellular vesicles in atherogenesis. The mechanisms of efferocytosis impairment and its significance in atherosclerotic vulnerable plaque formation are discussed. The data on the pro- and anti-inflammatory effects of apoptotic extracellular vesicular particles are presented

The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts

Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior