Background The degeneration of the cholinergic circuit from the basal forebrain to the hippocampus contributes to memory loss in patients suffering from Alzheimer’s disease (AD). However, the internal relationships between the acetylcholine (Ach) cycle and memory decline during the early stages of AD currently remain unknown. Here, we investigate the mechanisms underlying the activation of the cholinergic circuit and its impact on learning and memory using APP/PS1 mice models. Methods Novel object recognition and Morris water maze tests were used to measure learning and memory function. Magnetic resonance spectrum (MRS) imaging was applied to longitudinally track changes in neurochemical metabolism in APP/PS1 mice aged 2, 4, 6, and 8 months. The number of neurons and the deposition of Aβ plaques were measured using Nissl, immunohistochemistry, and Thioflavin S staining. We then employed a chemogenetic strategy to selectively activate the cholinergic circuit from the medial septal nucleus (MS) and the vertical limb of the diagonal band nucleus (VDB) on the basal forebrain to the hippocampus. MRS and immunoblotting techniques were used to measure the neurochemical metabolism levels and cholinergic-related proteins, respectively. Results We found that the levels of choline (Cho) in the basal forebrain were markedly higher compared to other brain regions and that its decrease along with N-acetyl aspartate (NAA) levels in the hippocampus was accompanied by memory deficits in APP/PS1 mice aged 4, 6, and 8 months. In terms of pathology, we observed that the deposition of Aβ plaques gradually aggravated throughout the cerebral cortex and hippocampus in APP/PS1 mice aged 6 and 8 months, while no Aβ deposition was detected in the basal forebrain. In contrast, the activity of choline acetyltransferase (ChAT) enzyme in the basal forebrain was decreased at 6 months of age and the cholinergic neurons were lost in the basal forebrain at 8 months of age. In addition, the activation of the cholinergic circuit from the MS and VDB to the hippocampus using chemical genetics is able to improve learning and reduce memory impairment in APP/PS1 mice. Similarly, the levels of Cho in the basal forebrain; NAA in the hippocampus, as well as the expression of ChAT and vesicular acetylcholine transporter (vAchT) in the basal forebrain; and muscarinic acetylcholine receptor 2 (CHRM2) in the hippocampus all increased. Conclusions These findings demonstrate that the neurochemical Cho and NAA of the cholinergic circuit can be used as biomarkers to enable the early diagnosis of AD. In addition, memory impairment in APP/PS1 mice can be attenuated using chemical genetics-driven Ach cycle activity of the cholinergic circuit.

Previous fundamental and clinical research has shown that electroacupuncture (EA) at the acupoints of Quchi (LI11) and Zusanli (ST36) can successfully alleviate motor dysfunction following stroke. Additionally, it has been discovered that gut microbiota and their metabolites play an essential role in stroke. However, the relationship between the metabolites of gut microbiota and the efficacy of EA is still unclear. Therefore, the aim of this study was to evaluate the mechanism of EA at LI11 and ST36 in the treatment of motor dysfunction after middle cerebral artery occlusion/reperfusion (MCAO/R) in model rats by comparing the differences and correlation between different short-chain fatty acids (SCFAs) and the recovery of motor function. The results indicated that EA at LI11 and ST36 acupoints enhanced the neurological function, motor function, and infarct volume of MCAO/R rats. The levels of acetic acid, propionic acid, and total SCFAs were considerably lower in the MCAO/R group than in the sham group ( P < 0.05 ). Acetic acid, propionic acid, and total SCFA concentrations were substantially higher in the MCAO/R + EA group than in the MCAO/R group ( P < 0.05 ). Finally, Pearson correlation analysis revealed that the propionic acid concentration was substantially favorably connected with the duration on the rotarod ( r = 0.633 and P < 0.05 ) and highly negatively correlated with the modified neurological severity score (mNSS) ( r = − 0.698 and P < 0.05 ) and the percentage of cerebral infarct volume ( r = − 0.729 and P < 0.05 ). Taken together, these findings indicate that the increase in propionic acid may be one of the mechanisms and targets of EA at LI11 and ST36 acupoints to improve poststroke motor dysfunction in MCAO/R rats.

ObjectivesThis study was to investigated the efficacy of music therapy (MT) in children with autism spectrum disorder (ASD) via a meta-analysis that comprehensively evaluated data from all eligible research in this field.DesignSystematic review and meta-analysis.SettingA systematic search of the PubMed, Embase, and Cochrane Library databases from inception to October 2021 to identify studies that administered MT to children with ASD.ResultsEight randomized controlled trials (RCTs) including 608 participants met the inclusion criteria. The meta-analysis showed that MT was associated with a significant increase in social reactions among children with ASD (standardized mean difference (SMD) = 0.24, 95% confidence interval (CI) [0.03, 0.46], I2 = 0%, P = 0.03). However, MT did not elicit a significant increase in symptom severity (SMD = 0.17, 95% CI [−0.04,0.38], I2 = 0%,P = 0.12), social adaptive behavior (SMD = 0.02, 95% CI [−0.44,0.48], I2 = 0%,P = 0.93) or speech (SMD = 0.04, 95% CI [−0.39, 0.47], I2 = 0%, P = 0.86) in children with ASD.ConclusionMT can improve social skills in children with ASD; however, there does not seem to be a consensus on the persistence of its effects. These findings can inform clinical practice. Promoting the use of MT in children with ASD and improving its symptoms are the ultimate goals.

BackgroundTai Chi Chuan (TCC) is a physical activity modality that originated in China and is now widely popular around the world. Although there are a series of articles reporting that TCC can improve balance and other functional symptoms in a variety of populations, including the elderly, patients with stroke, and patients with Parkinson's disease, its efficiency has not been scientifically and methodically evaluated in subjects with functional ankle instability (FAI). Moreover, there is no literature directly comparing TCC and conventional balance training (CBT) interventions for FAI. The objective of this study is to investigate the comparative effects of TCC intervention and CBT protocols in improving postural balance and subjective instability feelings in patients with FAI.MethodsThis study will be a single-center, parallel group, randomized controlled trial. Sixty-eight patients with FAI will be included and randomly assigned in a 1:1 ratio to either an intervention group (n =34) or a control group (n = 34). The participants in the intervention group will complete 12 weeks of TCC intervention (40 min/time, 3 times/week for 12 weeks) on the basis of health education treatment. The control group will receive health education and 36 CBT sessions during a 12-week period. Outcome measures include postural stability and self-reported feelings of instability at baseline, after the end of the intervention, and 3-month follow-up. The postural stability assessment of patients with FAI will be detected by performing static and dynamic postural tests, which will be carried out through a specific balance platform (TecnoBody ProKin). Self-reported feelings of instability will be assessed by Cumberland Ankle Instability Tool (CAIT), American Orthopedics Foot and Ankle Society's Ankle–Hindfoot Evaluation Scale (AOFAS-AHES), and the MOS item Short Form Health Survey (SF-36).DiscussionThis trial will demonstrate whether a 12-week TCC intervention positively affects postural stability and self-reported outcomes in patients with FAI. At the same time, the superiority of its clinical efficacy will also be compared with that of CBT. This study may also help to redefine the value of traditional Chinese exercises in the treatment of chronic ankle instability.Clinical trial registrationChinese Clinical Trial Registry: ChiCTR2100041790. Registration date: 22 March 2021. http://www.chictr.org.cn/edit.aspx?pid=119501&amp;htm=4.