Considerable evidence suggest that a variety of Long-non-coding RNAs (LncRNAs) are widely implicated in several neurodegenerative disorders. The present study aims to investigate the regulatory effect of LncRNA 17A in an in vitro model of Alzheimer’s disease (AD). AD cell model was established by treating the SH-SY5Y cells with amyloid β peptide 1-42, and then the cells were transfected with 17A shRNA and pcDNA-17A. Apoptosis, migration, invasion and ELISA assays were performed to investigate the effect of differentiated 17A expression level on AD cell line. It was determined that 17A-overexpressing promotes autophagy, induces neurodegenration and deactivates GABAB signaling. In conclusion, our results demonstrated that the dysregulation of LncRNA 17A was involved in cellular functions and biological processes of neuroblastoma cells in an AD cell model, shedding light on the diagnostic value and therapeutic potential of LncRNA 17A for AD intervention.
It has been suggested that cerebral blood flow (CBF) alterations may be involved in the pathogenesis of Alzheimer's disease (AD). However, how CBF changes with age has not been detailed in AD, particularly in its early stages. The objective of the present study was to evaluate CBF in four brain regions (the hippocampus, entorhinal cortex, frontoparietal cortex and thalamus) of mice in four age groups, to mimic the respective stages of AD in humans [2 months (pre-clinical), 3.5 months (sub-clinical), 5 months (early-clinical) and 8 months (mid-clinical)], to understand the age-associated changes in selected brain regions and to elucidate the underlying vascular mechanisms. CBF was measured using magnetic resonance imaging-arterial spin labelling (ASL) under identical conditions across the age groups of AβPPSWE/PS1ΔE9 (APP/PS1) transgenic mice with AD. The results indicated age- and brain region-associated changes in CBF were associated with early AD. More precisely, an age-dependent increase in CBF (in the pre- and sub-clinical AD groups) was observed in the frontoparietal cortex and thalamus. Conversely, increased CBF demonstrated an age-dependent decline (in the early- and mid-clinical AD groups) in all examined brain regions. Among the regions, the thalamus had the greatest increase in CBF in the 2 and 3.5 months age groups, which was substantially different compared with the age-matched controls. An extension of vessel area was also noted to be age- and brain region-dependent. In particular, correlation analysis revealed significant associations of CBF with vessel area in the frontoparietal cortex and thalamus of APP/PS1 mice at ages 2 and 3.5 months, indicating that CBF increase may arise from vessel extension. The results of the present study suggested that ASL can detect age- and brain region-associated changes in CBF in mice with AD, and that ASL-measured CBF increase may be a potential diagnostic biomarker for early AD. The observation that CBF increase resulted from vessel extension may aid in the understanding of the vascular role in age-associated development of AD pathology, and provide preclinical evidence for AD patient management.
BackgroundmiR-15b is significantly and consistently downregulated in different clinical phenotypes of myasthenia gravis (MG). However, its role in pathogenesis of MG is still not clear. This study aimed to explore the function of miR-15b in MG.Material/MethodsBlood samples from early-onset MG, late-onset MG, thymoma patients, and healthy participants were collected. The expression pattern of IL-15 and miR-15b was identified by qRT-PCR and ELISA in patient serum and mouse tissue samples. The regulative role of miR-15b on IL-15 expression was verified in an experimental autoimmune myasthenia gravis (EAMG) mice model.ResultsqRT-PCR and ELISA showed that miR-15b expression was significantly lower and IL-15 expression was significantly higher in all EMG, LMG, and thymoma cases compared to healthy controls. Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice. Through searching in bioinformatics databases, we identified a highly conserved consequential pairing between IL-15 and miR-15b. Subsequent dual luciferase assay further verified this match.ConclusionsThis study is the first to report the miR-15b-IL-15 axis can directly regulate IL15 expression, which helps to further explain the abnormal IL-15 expression in MG patients and the pathogenesis of MG.
Bithalamic infarctions initially presenting as a convulsive seizure are rarely reported and, to our best knowledge, have never been reported in China. Here, we present a patient with convulsive seizure at the onset of bilateral paramedian thalamic infarction. The diffusion-weighted imaging revealed that the infarct area is supplied by Percheron artery. Associated with the relationship between seizure and centrencephalic system and reticular formation as previously reported, we suggest that seizure could be the onset symptom of paramedian thalamic infarction. Physicians should recognize this condition, because both seizure control and early ischemic stroke management are required.
Stroke caused by atherosclerosis remains a leading cause of morbidity and mortality worldwide, associated with carotid plaque rupture and inflammation progression. However, the inflammatory biomarkers which aid in predicting the future course of plaques are less detailed. The present study investigated the association between plaque vulnerable and inflammatory biomarkers using blood and plaque specimens. Carotid plaque specimens were obtained from 80 patients following stroke, 14 patients suffering from transient ischaemic attack and 17 asymptomatic patients that underwent carotid endarterectomy. To assess changes in plaque characteristics at histological levels, plaques were categorized by the time between the latest ischemic stroke and surgical intervention within 30, 30–90, 90–180 and over 180 days following stroke. Serum levels of inflammatory biomarkers interleukin (IL)-6, IL-10 and kinin B1 receptor (B1R) were measured by ELISA. Histological assessment of plaque was used to evaluate the plaque stability, progression and the inflammatory biomarker levels. Comparisons of histological characteristics demonstrated that plaques revealed an unstable phenotype following stroke within 30, 30–90 days and then remodeled into more stable plaques following stroke at 90–180 and over 180 days. By comparing the serum levels of inflammatory biomarkers, it was observed that IL-6 and B1R levels tended to decline whereas IL-10 levels increased in stroke patients from <30 days to over 180 days. Immunohistochemical analysis of IL-6, IL-10 and B1R demonstrated similar alterations in serum levels. Correlation analyses revealed that only B1R serum level was significantly correlated with histological level in patients with carotid atherosclerosis. The findings revealed that serum B1R levels may provide prognostic information and currently act as potential indicators for progression in atherosclerosis.
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