ABSTRACT
Demyelination is among the most conspicuous neurological sequelae of SARS-CoV-2 infection (COVID-19) in both the central (CNS) and peripheral (PNS) nervous systems. Several hypotheses have been proposed to explain the mechanisms underlying demyelination in COVID-19. However, none have considered the SARS-CoV-2's effects on the renin-angiotensin-aldosterone system (RAAS). Therefore, our objective in this review is to evaluate how RAAS imbalance, caused by direct and indirect effects of SARS-CoV-2 infection, could contribute to myelin loss in the PNS and CNS. In the PNS, we propose that demyelination transpires from two significant changes induced by SARS-CoV-2 infection, which include upregulation of ADAM-17 and induction of lymphopenia. Whereas, in the CNS, demyelination could result from RAAS imbalance triggering two alterations: (1) a decrease in angiotensin type II receptor (AT2R) activity, responsible for restraining defense cells' action on myelin; (2) upregulation of ADAM-17 activity, leading to impaired maturation of oligodendrocytes and myelin formation. Thus, we hypothesize that increased ADAM-17 activity and decreased AT2R activity play roles in SARS-CoV-2 infection-mediated demyelination in the CNS.
ABSTRACT
Abuse-related drug usage is a public health issue. Drosophila melanogaster has been used as an animal model to study the biological effects of these psychoactive substances in preclinical studies. Our objective in this review is to evaluate the adverse effects produced by cocaine, nicotine, and marijuana during the development of D. melanogaster. We searched experimental studies in which D. melanogaster was exposed to these three psychoactive drugs in seven online databases up to January 2023. Two reviewers independently extracted the data. Fifty-one studies met eligibility criteria and were included in the data extraction: nicotine (n = 26), cocaine (n = 20), and marijuana (n = 5). Fifteen studies were eligible for meta-analysis. Low doses (â¼0.6 mM) of nicotine increased locomotor activity in fruit flies, while high doses (≥3 mM) led to a decrease. Similarly, exposure to cocaine increased locomotor activity, resulting in decreased climbing response in D. melanogaster. Studies with exposure to marijuana did not present a profile for our meta-analysis. However, this drug has been less associated with locomotor changes, but alterations in body weight and fat content and changes in cardiac function. Our analyses have shown that fruit flies exposed to drugs of abuse during different developmental stages, such as larvae and adults, exhibit molecular, morphological, behavioral, and survival changes that are dependent on the dosage. These phenotypes resemble the adverse effects of psychoactive substances in clinical medicine.