Connexin 43 regulates astrocyte dysfunction and cognitive deficits in early life stress-treated mice.

Early life stress such as maternal separation (MS), is a major risk factor for developing psychiatric disorders in adulthood. Connexin 43 (CX43), the main type of connexins expressed in astrocytes, has been indicated to participate in depression disorders. Nevertheless, the role of CX43 in MS-induced cognitive impairment and astrocyte dysfunction is unclear. Neonatal C57BL/6 mice were exposed to MS to mimic early life stress. Adeno-associated virus carrying CX43 was inoculated into mice for CX43 overexpression. Sucrose preference test, forced swim test and Morris water maze were performed for evaluating depression-like behaviors and spatial learning and memory of mice in adulthood. Real time quantitative polymerase chain reaction was conducted to detect CX43 mRNA expression in mouse brain. Immunofluorescence staining and western blotting were used for measuring expression levels of astrocytic markers in murine hippocampal dentate gyrus. The results showed that overexpressing CX43 attenuated MS exposure-induced depression-like behaviors and decrease in spatial learning and memory in mice. Upregulating CX43 alleviated MS exposure-induced downregulation of astrocytic markers. Collectively, CX43 overexpression attenuates cognitive deficits and astrocyte dysfunction in mice exposed to MS.

Partitioning indoor-generated and outdoor-generated PM2.5 from real-time residential measurements in urban and peri-urban Beijing.

Limited number of projects have attempted to partition and quantify indoor- and outdoor-generated PM2.5 (PM2.5ig and PM2.5og) where strong indoor sources (e.g., solid fuel, tobacco smoke, or kerosene) exist. This study aimed to apply and refine a previous recursive model used to derive infiltration efficiency (Finf) to additionally partition pollution concentrations into indoor and outdoor origins within residences challenged by elevated ambient and indoor combustion-related sources. During the winter of 2016 and summer of 2017 we collected residential measurements in 72 homes in urban and peri-urban Beijing, 12 of which had additional paired residential outdoor measurements during the summer season. Local ambient measurements were collected throughout. We then compared the calculated PM2.5ig and using (i) outdoor and (ii) ambient measurements as model inputs. The results from outdoor and ambient measurements were not significantly different, which suggests that ambient measurements can be used as a model input for pollution origin partitioning when paired outdoor measurements are not available. From the results calculated using ambient measurements, the mean percentage contribution of indoor-generated PM2.5 was 19 % (σ = 22 %), and 7 % (11 %) of the total indoor PM2.5 for peri-urban and urban homes respectively during the winter; and 18 % (18 %) and 6 % (10 %) of the total indoor PM2.5 during the summer. Partitioning pollution into PM2.5ig and PM2.5og is important to allow investigation of distinct associations between health outcomes and particulate mixes, often with different physiochemical composition and toxicity. It will also inform targeted interventions that impact indoor and outdoor sources of pollution (e.g., domestic fuel switching vs. power generation), which are typically radically different in design and implementation.

Long non-coding RNA ANRIL knockdown suppresses apoptosis and pro-inflammatory cytokines while enhancing neurite outgrowth via binding microRNA-125a in a cellular model of Alzheimer's disease.

The present study aimed to investigate the effect of the long non-coding RNA antisense non-coding RNA in the INK4 locus (lnc-ANRIL) knockdown on apoptosis, neurite outgrowth and inflammation based on a PC12 cellular Alzheimer's disease (AD) model. A cellular AD model was constructed by treating nerve growth factor stimulated PC12 cells with amyloid ß (Aß) 1-42 and then control knockdown plasmid and lnc-ANRIL knockdown plasmid were transfected in the PC12 cellular AD model as the KD- negative control (NC) group or the AD-ANRIL group respectively. Apoptosis, neurite outgrowth, pro-inflammatory cytokines and microRNA (miR)-125a were assessed. Rescue experiments were conducted by transfecting lnc-ANRIL knockdown plasmid and lnc-ANRIL knockdown plasmid and miR-125a inhibitor in the PC12 cellular AD model as the KD-ANRIL group or KD-ANRIL + KD-miR-125a group respectively. Following transfection, cell apoptosis deccreased while neurite outgrowth increased in the KD-ANRIL group compared with the KD-NC group (all P<0.01). Concerning inflammation, tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß, IL-6 and IL-17 were decreased in the KD-ANRIL group compared with the KD-NC group (all P<0.01). miR-125a was negatively regulated by lnc-ANRIL and therefore rescue experiments were subsequently conducted. In the rescue experiments, cell apoptosis was increased while total neurite outgrowth was inhibited in the KD-ANRIL + KD-miR-125a group compared with the KD-ANRIL group (all P<0.01), and TNF-α, IL-1ß, IL-6 and IL-17 were increased in the KD-ANRIL + KD-miR-125a group compared with the KD-ANRIL group (all P<0.01). A luciferase reporter assay demonstrated that lnc-ANRIL directly bound miR-125a. lnc-ANRIL knockdown suppressed cell apoptosis and inflammation while promoting neurite outgrowth via binding of miR-125a in AD.

The influence of GAPT extraction on synapse loss of APPswe/PS1dE9 transgenic mice via adjusting Bcl-2/Bax balance.

INTRODUCTION: The degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how ß amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice. METHODS: Three-month and six-month APPswe/PS1dE9 transgenic mice were used. Spatial and memory ability were measured by Morris Water Maze, Neuron and synapse number were assessed by electron microscope; Aß, Bcl-2/Bax were determined by immunohistochemistry and western blot. RESULTS: APP/PS1 mice not only had increased Aß accumulation, impaired memory performance, less synapse number, and much more necrosed neurons, but also had significant reduction in the Bcl-2/Bax ratio. However, GAPT and donepezil showed improved memory performance, less Aß accumulation, increased neuron and synapse number, as well as restored balance of Bcl-2/Bax. DISCUSSION: GAPT may improve cognitive functions via both reducing Aß deposition and restoring Bcl-2/Bax balance of neuron.