RESUMO
Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disease. The predominant pathology of PD is the loss of dopaminergic cells in the substantia nigra. Cell transplantation is a strategy with significant potential for treating PD; mesenchymal stem cells (MSCs) are a tremendous therapeutic cell source because they are easily accessible. MSC-derived exosomes with potential protective action in lesioned sites serve as an essential promoter of neuroprotection, and neurodifferentiation, by modulating neural stem cells, neurons, glial cells, and axonal growth in vitro and in vivo environments. The biological properties of MSC-derived exosomes have been proposed as a beneficial tool in different pathological conditions, including PD. Therefore, in this review, we assort the current understanding of MSC-derived exosomes as a new possible therapeutic strategy for PD by providing an overview of the potential role of miRNAs as a component of exosomes in the cellular and molecular basis of PD.
Assuntos
Exossomos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/patologia , Exossomos/patologia , Neurônios Dopaminérgicos/patologiaRESUMO
Prenatal opioids exposure negatively affects the neurobehavioral abilities of children born from dependence dams. Adolescent housing conditions can buffer the detrimental impacts of early life experiences or contradictory can worsen individual psychosocial functions. The present study investigated the effects of maternal morphine dependence and different rearing conditions on behaviors and protein expression in brain reward circuits of male pups. Female Wistar rats a week before conception, during pregnancy and lactation were injected twice daily with escalating doses of morphine or saline. On a postnatal day 21, male pups were weaned and subjected to three different environments for two months: standard (STD), isolated (ISO), or enriched environment (EE). The anxiety and drug-related reward were measured using elevated plus maze, open field test, and conditioned place preference. Western blotting was used to determine the protein level of ΔFosB and µ-opioid receptor proteins in the striatum and the midbrain of male offspring, respectively. Results showed that maternal morphine administration dramatically increased anxiety-like and morphine place preference behaviors in offspring. Also, ISO condition aggravated these behavioral outcomes. While, rearing in EE could attenuate anxiety and morphine conditioning in pups. At molecular levels, maternal morphine exposure and social isolation markedly increased both of ΔFosB and µ-opioid receptor proteins expression. However, rearing in the EE declined ΔFosB protein expression. Together, these findings help to elucidate long lasting impacts of early life morphine exposure and rearing environment on the behavioral and molecular profile of addicted individuals.