Altered GluN2B NMDA receptor function and synaptic plasticity during early pathology in the PS2APP mouse model of Alzheimer's disease

AbstractGluN2B subunit containing NMDARs (GluN2B-NMDARs) mediate pathophysiological effects of acutely applied amyloid beta (Aβ), including impaired long-term potentiation (LTP). However, in transgenic Alzheimer's disease (AD) mouse models which feature gradual Aβ accumulation, the function of GluN2B-NMDARs and their contribution to synaptic plasticity are unknown. Therefore, we examined the role of GluN2B-NMDARs in synaptic function and plasticity in the hippocampus of PS2APP transgenic mice. Although LTP induced by theta burst stimulation (TBS) was normal in PS2APP mice, it was significantly reduced by the selective GluN2B-NMDAR antagonist Ro25-6981 (Ro25) in PS2APP mice, but not wild type (wt) mice. While NMDARs activated by single synaptic stimuli were not blocked by Ro25, NMDARs recruited during burst stimulation showed larger blockade by Ro25 in PS2APP mice. Thus, the unusual dependence of LTP on GluN2B-NMDARs in PS2APP mice suggests that non-synaptic GluN2B-NMDARs are activated by glutamate that spills out of synaptic cleft during the burst stimulation used to induce LTP. While long-term depression (LTD) was normal in PS2APP mice, and Ro25 had no impact on LTD in wt mice, Ro25 impaired LTD in PS2APP mice, again demonstrating aberrant GluN2B-NMDAR function during plasticity. Together these results demonstrate altered GluN2B-NMDAR function in a model of early AD pathology that has implications for the therapeutic targeting of NMDARs in AD

The Efficacy of Moxibustion and Acupuncture Therapy for Ankylosing Spondylitis: A Protocol for an Overview of Systematic Reviews and Meta-analyses

Abstract Background:Ankylosing Spondylitis (AS) is a complex and progressive autoimmune inflammatory disease with a worldwide prevalence ranging up to 0.9%. Several systematic reviews and meta-analyses of traditional Chinese medicine alternative therapies, such as acupuncture or moxibustion, have demonstrated the effectiveness of moxibustion and acupuncture in the treatment of ankylosing spondylitis. However, there is no relevant literature to comprehensively evaluate the evidence.The purpose of this overview is to synthesize and evaluate the reliability of evidence generated in the systematic review (SR) and meta-analysis of moxibustion and acupuncture as a primary or complementary therapy for patients with ankylosing spondylitis.Methods:PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure[CNKI], Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database[CBM] were searched for systematic reviews and Meta-analysis that review the efficacy of acupuncture or moxibustion as the primary treatment for patients with Ankylosing Spondylitis. The literature published before August 2020 will be selected. Additionally, the relevant SRs and Meta-analyses that unpublished or ongoing will be searched in PROSPERO and INPLASY. The methodological guidelines for overviews will be used to reviews and extract data by two reviewers, and their will do it independently.Methodology quality will be analyzed by the AMSTAR-2 and the risk of bias by POBIS. For the included studies, we will adopt the following results as primary evaluation indicators: effective rate, Visual Analogue Scale (VAS) and Bath AS Disease Activity Index (BASDAI). Reviewers will assess the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation(GRADE).Results: The results will be published in a peer-reviewed journal. Conclusion: This overview will provide comprehensive evidence of moxibustion and acupuncture for patients with Ankylosing Spondylitis. Registration number: INPLASY202080035</jats:p