miR-29c-3p regulates TET2 expression and inhibits autophagy process in Parkinson's disease models.

Autophagy in dopamine (DA) neurons is concerned to be associated with Parkinson's disease (PD), but the detailed mechanism remains unknown. Herein, we aimed to investigate the function of microRNA (miR)-29c-3p in autophagy in PD models. Intraperitoneal injection of MPTP (20 mg/kg) was given to C57BL/6 mice to establish PD mouse model. SH-SY5Y cells were treated with MPP+ (1 mmol/L) to establish in vitro PD model. The results indicated that in the substantia nigra pars compacta (SNpc) DA neurons of PD mice, autophagy was activated accompanied by down-regulated miR-29c-3p and up-regulated ten-eleven translocation 2 (TET2) expression. Up-regulation of miR-29c-3p inhibited TET2 expression and SNpc (including DA neurons) autophagy in PD mice. In vitro PD model confirmed that MPP+ treatment markedly down-regulated miR-29c-3p expression and up-regulated TET2 expression in SH-SY5Y cells in a dose/time-dependent manner. Moreover, miR-29c-3p up-regulation also inhibited autophagy and TET2 expression in vitro. Additionally, TET2 was proved to be targeted and down-regulated by miR-29c-3p. TET2 knockdown inhibited MPP+ -induced autophagy, whereas TET2 over-expression reversed the effects of miR-29c-3p over-expression on SH-SY5Y cell autophagy. Overall, miR-29c-3p over-expression inhibits autophagy in PD models, which may be mediated by TET2. Our finding may provide new insights for regulating autophagy to improve PD progression.

Effects of Prenatal Methamphetamine Exposure on Birth Outcomes, Brain Structure, and Neurodevelopmental Outcomes.

This study reviews the findings from previous research on the effects of prenatal methamphetamine (MA) exposure on birth outcomes, brain structure, and neurodevelopmental outcomes of the offspring. These findings indicate that prenatal MA exposure may lead to shorter gestational age, lower birth weight, lower head circumference, and shorter body length of neonatal, structural brain changes, and impairment in cognitive development, motor development, inhibitory control, and attention of children from 1 to 15 years. Based on these findings of the previous cohort studies on the effect of prenatal MA exposure on the birth outcomes and childhood outcomes of the offspring, we conclude by discussing the shortcomings and inconsistencies of previous studies in each section. A multicenter, large-scale population-based prospective cohort study is needed to establish and seek the differences and similarities of the pathological changes in different systems among offspring prenatally exposed to MA in different periods. And the pathophysiology mechanism underlying these changes should be studied by the method of omics technology in future. These efforts are of great significance to address the adverse health outcomes caused by prenatal MA exposure.

Isorhapontigenin prevents ß­amyloid­associated cognitive impairments through activation of the PI3K/AKT/GSK­3ß pathway.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. Aß1­42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti­tumor, and anti­inflammatory effects. However, it is still unclear whether ISO can affect ß­amyloid­associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by Aß1­42 in rats. It inhibited the Aß­induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta­induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated Aß­induced inflammation and oxidative stress by activating the PI3K/AKT/GSK­3ß pathway and ultimately improved cognitive dysfunction in AD rats.