NEAT1 inhibits the angiogenic activity of cerebral arterial endothelial cells by inducing the M1 polarization of microglia through the AMPK signaling pathway.

BACKGROUND: Enhancing angiogenesis may be an effective strategy to promote functional recovery after ischemic stroke. Inflammation regulates angiogenesis. Microglia are crucial cells that initiate inflammatory responses after various brain injuries. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a role in regulating brain injury. This study aimed to explore the effects of NEAT1-regulated microglial polarization on the neovascularization capacity of cerebrovascular endothelial cells and the underlying molecular regulatory mechanisms. METHODS: Mouse cerebral arterial endothelial cells (mCAECs) were co-cultured with BV-2 cells in different groups using a Transwell system. NEAT1 expression levels were measured by fluorescence quantitative reverse transcription PCR. Levels of IL-1ß, IL-6, TNF-α, Arg-1, IL-4, and IL-10 were determined using ELISA. Expression levels of CD86 and CD163 were detected by immunofluorescence. The neovascularization capacity of mCAECs was assessed using CCK-8, Transwell, Transwell-matrigel, and tube formation assays. Label-free quantification proteomics was carried out to identify differentially expressed proteins. Protein levels were measured by Western blotting. RESULTS: NEAT1 overexpression induced M1 polarization in BV-2 cells, whereas NEAT1 knockdown blocked lipopolysaccharide-induced M1 polarization in microglia. NEAT1-overexpressing BV-2 cells suppressed the angiogenic ability of mCAECs, and NEAT1-knocking BV-2 cells promoted the angiogenic ability of mCAECs under lipopolysaccharide treatment. Label-free quantitative proteomic analysis identified 144 upregulated and 131 downregulated proteins that were induced by NEAT1 overexpression. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed proteins. Further verification showed that NEAT1 inactivated the AMPK signaling pathway. Moreover, the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide reversed the effect of NEAT1 on BV-2 polarization and the regulatory effect of NEAT1-overexpressing BV-2 cells on the angiogenic ability of mCAECs. CONCLUSIONS: NEAT1 inhibits the angiogenic activity of mCAECs by inducing M1 polarization of BV-2 cells through the AMPK signaling pathway. This study further clarified the impact and mechanism of NEAT1 on microglia and the angiogenic ability of cerebrovascular endothelial cells.

Effects of aerobic exercise on cognitive function in adults with major depressive disorder: A systematic review and meta-analysis.

Background: Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder that impairs the cognitive function of individuals. Aerobic exercise stands out as a promising non-pharmacological intervention for enhancing cognitive function and promoting brain health.While positive impacts of aerobic exercise on executive function in adults with depression have been documented, a comprehensive understanding of its benefits on overall cognitive function, including memory, attention, and processing speed, along with key moderating factors in adults with MDD, remains unexplored. The purpose of the systematic review and meta-analysis was to investigate the effects of aerobic exercise on overall cognitive function in adults with MDD, and to explore whether cognitive sub-domains, aerobic exercise characteristics, and study and sample variables modify the effects of aerobic exercise on cognition. Methods: Six English electronic databases (Embase, Cochrane Central, Scopus, APA PsycInfo, PubMed, Web of Science) were searched from inception to 2 April 2023. Randomized trials, including adults aged 18 years or above with a diagnosis of clinical depression, of the effects of aerobic exercise on cognitive function in adults with MDD compared to non-aerobic exercise groups were included. A three-level meta-analysis was conducted utilizing a random-effects model in R. The quality of the studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. The PROSPERO registration number is CRD42022367350. Results: Twelve randomized trials including 945 adults with MDD were included. Results indicated that aerobic exercise significantly improved overall cognitive function (g = 0.21; 95 % confidence intervals [CI] = 0.07, 0.34), and the sub-domains of memory (g = 0.25; 95 % CI = 0.06, 0.44) and executive function (g = 0.12; 95 % CI = 0.04, 0.20). Significant benefits in cognitive function were found from moderate-to-vigorous (mixed) intensity (g = 0.19; 95 % CI = 0.02, 0.37), aerobic exercise conducted 3 times per week (g = 0.23; 95 % CI = 0.10, 0.38), in sessions < 45 min (g = 0.59; 95 % CI = 0.28, 0.90), and 45-60 min (g = 0.16; 95 % CI = 0.07, 0.26), in aerobic exercise intervention ≤ 12 weeks (g = 0. 26; 95 % CI = 0.08, 0.44). Limitations: This review only included peer-reviewed English-language studies, which may lead to a language bias. The results of the Egger's test suggested a potential publication bias. Conclusions: Aerobic exercise is efficacious in improving overall cognitive function and the sub-domains of memory and executive function in adults with major depressive disorder.