RESUMO
Introduction: Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD. However, neurobiological performance of patients with both AD and SLD in previous studies is inconsistent, and identifying specific patterns of the brain functional network and structural characteristics in this kind of comorbidity is warranted for understanding how AD and SLD symptoms interact with each other as well as finding effective clinical intervention. Thus, the aims of this systematic review were to summarize the relevant findings and their limitations and provide future research directions. Methods: A systematic search on brain functional and structural changes in patients with both AD and SLD was conducted from PubMed, Web of Science, and EMBASE databases. Results: Nine original articles published between 2009 and 2021 were included with a total of 328 patients with comorbid AD and SLD, 367 patients with only AD, and 294 healthy controls. One single-photon emission computed tomography study and one multislice spiral computed tomography perfusion imaging study investigated changes of cerebral blood flow; four structural magnetic resonance imaging (MRI) studies investigated brain structural changes, two of them used whole brain analysis, and another two used regions of interest; two resting-state functional MRI studies investigated brain functional changes, and one 2-deoxy-2-(18F)fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD. Findings were inconsistent, ranging from default mode network to sensorimotor cortex, hippocampus, brain stem, and pineal gland, which may be due to different imaging techniques, measurements of sleep disorder and subtypes of AD and SLD. Conclusions: Our review provides a systematic summary and promising implication of specific neuroimaging dysfunction underlying co-occurrence of AD and SLD. However, limited and inconsistent findings still restrict its neurobiological explanation. Further studies should use unified standards and comprehensive brain indices to investigate the pathophysiological basis of interaction between AD and SLD symptoms in the development of the disease spectrums.
RESUMO
Sensorineural hearing loss (SNHL) is a common causes of disability. Neural stem cells (NSCs) from the cochlear nuclei have been considered to be a potential direction for the treatment of SNHL. Neuregulin 1 (NRG1)/ErbB2 signaling displays an essential role in nervous system development. In this study, we aimed to explore the roles of NRG1/ErbB2 in differentiation and apoptosis of cochlear nuclei NSCs. The data showed that the expression of NGR1 and ErbB2 in cochlear nuclei NSCs isolated from rats were increased with the age of rats. NRG1 treatment reduced the nestin-positive cells number, increased the MAP2-positive and GFAP-positive cells number, decreased the expression of cleaved-caspase-3, and increased the activation of PI3K/AKT. ErbB2 knockdown by lentiviral-mediated ErbB2 shRNA infection reversed the effect of NRG1 on cochlear nuclei NSCs. LY294002 administration further enhanced the effect of ErbB2 silencing on the expression of nestin, MAP2, GFAP and cleaved-caspase-3. Taken together, NRG1/ErbB2 regulates differentiation and apoptosis of cochlear nucleus NSCs through PI3K/Akt pathway.
