No abstract

Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1.5 g/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 and 10 mg/kg) was given before intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4–9 (an equivalent to the third trimester of human pregnancy). Spatial memory/reversal learning and rewarding ethanol effect were evaluated in adult (PND60–70) rats. Additionally, the impact of rapamycin pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the brain was assessed in adult rats. Our results show that neonatal ethanol exposure induced deficits in spatial memory and reversal learning in adulthood, but the reversal learning outcome may have been due to spatial learning impairments rather than cognitive flexibility impairments. Furthermore, in adulthood the ethanol treated rats were also more sensitive to the rewarding effect of ethanol than the control group. Rapamycin prevented the neonatal effect of ethanol and normalized the GluN2B down-regulation in the hippocampus and the prefrontal cortex, as well as normalized this subunit’s up-regulation in the striatum of adult rats. Our results suggest that rapamycin and related drugs may hold promise as a preventive therapy for fetal alcohol spectrum disorders.

Drug dependence is an escalating problem worldwide and many efforts are being made to understand the molecular basis of addiction. The morphine model is widely used in these investigations. To date, at least 29 studies exploring the influence of morphine on mammals' proteomes have been published. Among various proteins indicated as up- or down-regulated, the expression changes of enzymes engaged in energy metabolism pathways have often been confirmed. To verify whether proteomics-indicated alterations in enzyme levels reflect changes in their activity, four enzymes: PK, MDH, Complex I, and Complex V were investigated in morphine addiction and abstinence models. After analyses of the rat brain mitochondria fraction in the model of morphine dependence, we found that one of the investigated enzymes (pyruvate kinase) showed statistically significant differences observed between morphine, control, and abstinence groups. J. Cell. Biochem. 118: 4323-4330, 2017. © 2017 Wiley Periodicals, Inc.

An unprecedented effort to tackle the ongoing COVID-19 pandemic has characterized the activity of the global scientific community over the last two years. Hundreds of published studies have focused on the comprehension of the immune response to the virus and on the definition of the functional role of SARS-CoV-2 proteins. Proteins containing zinc fingers, both belonging to SARS-CoV-2 or to the host, play critical roles in COVID-19 participating in antiviral defenses and regulation of viral life cycle. Differentially expressed zinc finger proteins and their distinct activities could thus be important in determining the severity of the disease and represent important targets for drug development. Therefore, we here review the mechanisms of action of host and viral zinc finger proteins in COVID-19 as a contribution to the comprehension of the disease and also highlight strategies for therapeutic developments.

No abstract