BackgroundPreventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent.ResultsHere, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples.ConclusionsThese results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-015-0056-1) contains supplementary material, which is available to authorized users.

IMPORTANCE Determining the long-term impact of COVID-19 on cognition is important to inform immediate steps in COVID-19 research and health policy.OBJECTIVE To investigate the 1-year trajectory of cognitive changes in older COVID-19 survivors.DESIGN, SETTING, AND PARTICIPANTS This cohort study recruited 3233 COVID-19 survivors 60 years and older who were discharged from 3 COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. Their uninfected spouses (N = 466) were recruited as a control population. Participants with preinfection cognitive impairment, a concomitant neurological disorder, or a family history of dementia were excluded, as well as those with severe cardiac, hepatic, or kidney disease or any kind of tumor. Follow-up monitoring cognitive functioning and decline took place at 6 and 12 months. A total of 1438 COVID-19 survivors and 438 control individuals were included in the final follow-up. COVID-19 was categorized as severe or nonsevere following the American Thoracic Society guidelines. MAIN OUTCOMES AND MEASURES The main outcome was change in cognition 1 year after patient discharge. Cognitive changes during the first and second 6-month follow-up periods were assessed using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview of Cognitive Status-40, respectively. Based on the cognitive changes observed during the 2 periods, cognitive trajectories were classified into 4 categories: stable cognition, early-onset cognitive decline, late-onset cognitive decline, and progressive cognitive decline. Multinomial and conditional logistical regression models were used to identify factors associated with risk of cognitive decline.RESULTS Among the 3233 COVID-19 survivors and 1317 uninfected spouses screened, 1438 participants who were treated for COVID-19 (691 male [48.05%] and 747 female [51.95%]; median [IQR] age, 69 [66-74] years) and 438 uninfected control individuals (222 male [50.68%] and 216 female [49.32%]; median [IQR] age, 67 [66-74] years) completed the 12-month follow-up. The incidence of cognitive impairment in survivors 12 months after discharge was 12.45%. Individuals with severe cases had lower Telephone Interview of Cognitive Status-40 scores than those with nonsevere cases and control individuals at 12 months (median [IQR]: severe, 22.50 [16.00-28.00]; nonsevere, 30.00 [26.00-33.00]; control , 31.00 [26.00-33.00]). Severe COVID-19 was associated with a higher risk of early-onset cognitive decline (odds ratio [OR], 4.87; 95% CI, 3.30-7.20), late-onset cognitive decline (OR, 7.58; 95% CI, 3.58-16.03), and progressive cognitive decline (OR, 19.00; 95% CI, 9.14-39.51), while nonsevere COVID-19 was associated with a higher risk of early-onset cognitive decline (OR, 1.71; 95% CI, 1.30-2.27) when adjusting for age, sex, education level, body mass index, and comorbidities. CONCLUSIONS AND RELEVANCEIn this cohort study, COVID-19 survival was associated with an increase in risk of longitudinal cognitive decline, highlighting the import...

Increasing evidences have demonstrated that inflammation is involved in the mechanisms of acute ischemic stroke (AIS). As an important and easy-to-measure inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) shows a high association with mortality in patients with stroke in recent studies. In this study, we evaluated the prognostic role of NLR in patients with AIS. One hundred forty-three patients with AIS were enrolled. Clinical data were collected and the NLR was calculated from the admission blood work. The patients were followed up for 3 months after stroke onset. The occurrence of death and the major disability at 3 months after onset were end points in this study. Modified Rankin Scale score ≥3 was considered as poor outcome. In this study, 75 patients (52%) had poor outcome. We used binary logistic regression model to evaluate risk factor for poor outcome of AIS and found that the NLR was independently associated with the poor outcome of 3 months (P < 0.001). The optimal cutoff value for NLR as a predictor for 3-month outcome was 2.995. Therefore, in our study, high NLRs inversely predicted 3-month outcome in patients with AIS.

Adipose-derived stem cells (ADSCs) have been demonstrated to promote cerebral vascular remodeling processes after stroke. However, the exact molecular mechanism by which ADSCs exert protective roles in ischemic stroke is still poorly understood. In this study, we identified the role of exosomal microRNA-181b-5p (181b-Exos) in regulating post-stroke angiogenesis. The results of migration assay and capillary network formation assay showed that exosomes secreted by ADSCs (ADSCs-Exos) promoted the mobility and angiogenesis of brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD). Quantitative real-time polymerase chain reaction (qRT-PCR) showed that microRNA-212-5p (miR-212-5p) and miR-181b-5p were upregulated in BMECs subjected to the brain extract of the middle cerebral artery occlusion rats. The migration distance and tube length were increased in BMECs cultured with 181b-Exos. Furthermore, we identified that transient receptor potential melastatin 7 (TRPM7) was a direct target of miR-181b-5p. TRPM7 mRNA and protein levels were declined in BMECs cultured with 181b-Exos, but not in BMECs cultured with 212-Exos. Overexpression of TRPM7 reversed the effects of 181b-Exos on migration and tube formation of BMECs. In addition, 181b-Exos upregulated the protein expression of hypoxia-inducible factor 1α and vascular endothelial cell growth factor, and downregulated the protein expression of tissue inhibitor of metalloproteinase 3. The regulatory effect of 181b-Exos was attenuated by overexpressing TRPM7. Altogether, ADSCs-Exos promote the angiogenesis of BMECs after OGD via miR-181b-5p/TRPM7 axis, suggesting that ADSCs-Exos may represent a novel therapeutic approach for stroke recovery.

Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitters deficiency and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors, and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integrationsite-1 (Ahi1) KO mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.