Chronic neuroinflammation is an integral pathological feature of major neurodegenerative diseases. The recruitment of microglia to affected brain regions and the activation of these cells are the major events leading to disease-associated neuroinflammation. In a previous study, we showed that neuron-released α-synuclein can activate microglia through activating the Toll-like receptor 2 (TLR2) pathway, resulting in proinflammatory responses. However, it is not clear whether other signaling pathways are involved in the migration and activation of microglia in response to neuron-released α-synuclein. In the current study, we demonstrated that TLR2 activation is not sufficient for all of the changes manifested by microglia in response to neuron-released α-synuclein. Specifically, the migration of and morphological changes in microglia, triggered by neuron-released α-synuclein, did not require the activation of TLR2, whereas increased proliferation and production of cytokines were strictly under the control of TLR2. Construction of a hypothetical signaling network using computational tools and experimental validation with various peptide inhibitors showed that β1-integrin was necessary for both the morphological changes and the migration. However, neither proliferation nor cytokine production by microglia was dependent on the activation of β1-integrin. These results suggest that β1-integrin signaling is specifically responsible for the recruitment of microglia to the disease-affected brain regions, where neurons most likely release relatively high levels of α-synuclein.

Background Frequent Emergency Department (ED) visitors are identified by the policymakers to reduce avoidable ED visits and lessen the financial and operational burden. This study aimed to identify the factors related to the frequent use of ED services. Methods This nationwide, cross-sectional observational study was conducted using information obtained from the 2019 National Emergency Department Information System (NEDIS) database. Frequent ED users were defined as patients with four or more ED visits a year. We performed multiple logistic regression analyses to verify the relationship among sociodemographic characteristics, residential characteristics, clinical characteristics, and frequency of ED visits. Results Among 4,063,640 selected patients, 137,608 patients visited the ED four or more times a year (total number of visits = 735,502 times), which accounted for 3.4% and 12.8% of the total number of ED users and ED visits, respectively. A high ED visit frequency was associated with male sex, age < 9 or ≥ 70 years, Medical Aid (based on the insurance type), lower number of medical institutions and beds compared with that of the national average, and conditions, such as cancer, diabetes, renal failure, and mental illness. A low ED-visit frequency was associated with residence in regions vulnerable to emergency medical care and regions with high income. The possibility of frequent ED visits was high for patients with level 5 severity (non-emergent) and those with an increased need for medical treatment, including older patients and patients with cancer or mental illness. The possibility of frequent ED visits was low for patients aged > 19 years with level 1 severity (resuscitation). Conclusions Health service accessibility factors, including low income and medical resource imbalance, were associated with frequent ED visits. Future large-scale prospective cohort studies are warranted to establish an efficient emergency medical system.