Electroacupuncture alleviates PTSD-like behaviors by modulating hippocampal synaptic plasticity via Wnt/ß-catenin signaling pathway.

Abnormalities in hippocampal synaptic plasticity contribute to the pathogenesis of post-traumatic stress disorder (PTSD). The Wnt/ß-catenin signaling pathway is critical for the regulation of synaptic plasticity. PTSD symptoms can be alleviated by correcting impaired neural plasticity in the hippocampus (Hipp). Electroacupuncture (EA) has a therapeutic effect by relieving PTSD-like behaviors. However, little is known about whether the Wnt/ß-catenin pathway is involved in EA-mediated improvements of PTSD symptoms. In this study, we found that enhanced single prolonged stress (ESPS)-induced PTSD led to abnormal neural plasticity, characterized by the decline of dendritic spines, the expression of postsynaptic density 95 (PSD95), and synaptophysin (Syn) in the stressed Hipp along with the reduction of Wnt3a and ß-catenin, and increased GSK-3ß. EA significantly alleviated PTSD-like behaviors, as assessed by the open field test, elevated platform maze test and conditioning fear test. This was paralleled by correcting abnormal neural plasticity by promoting the expression of PSD95 and Syn, as well as the number of dendritic spines in the Hipp. Importantly, EA exerted anti-PTSD effects by augmenting the expression levels of Wnt3a and ß-catenin, and decreasing that of GSK-3ß. The effects mediated by EA were abolished by XAV939, an inhibitor of the Wnt/ß-catenin pathway. This suggests that EA relieved ESPS-induced PTSD-like behaviors, which can largely be ascribed to impaired neural plasticity in the Hipp. These findings provide new insights into possible mechanisms linking neural plasticity in the Hipp as potential novel targets for PTSD treatment in EA therapy.

Activation of the Hippocampal LXRß Improves Sleep-Deprived Cognitive Impairment by Inhibiting Neuroinflammation.

Sleep deprivation (SD) leads to cognitive impairment due to neuroinflammation associated with impaired hippocampal neuronal plasticity and memory processes. Liver X receptors (LXRs), including LXRα and LXRß isoforms, are crucial for synaptic plasticity and neuroinflammation. However, the potential roles of LXRs in the pathogenesis of cognitive impairment induced by SD remain unclear. We revealed that SD resulted in LXRß reduction in the hippocampus, which was associated with upregulated expression of high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB p65, and knockdown of hippocampal LXRß by shRNA (shLXRß) led to cognitive impairment. GW3965, a dual agonist for both LXRα and LXRß, ameliorated SD-induced cognitive impairment by inhibiting microglia activation, suppressing HMGB1/TLR4/NF-κB p65 pathway, and ultimately affecting the hippocampal expression of inflammatory cytokines in SD mice. LXRß knockdown by shLXRß abrogated the GW3965-mediated inhibition of the HMGB1/TLR4/NF-κB p65 pathway, therefore, abolishing the cognitive improvement. Moreover, inhibition of HMGB1 by glycyrrhizin (GLY) synergistic promoted GW3965-mediated anti-inflammation in activated microglia after lipopolysaccharide (LPS)/ATP stimulation and facilitated the cognitive improvement after GW administration by activating LXRß. All the data suggested that GW3965 ameliorated impaired cognition in SD mice by suppressing the HMGB1/TLR4/NF-κB p65 pathway followed LXRß activation. This study correlates a deficit of LXRß in cognitive dysfunction in SD associated with HMGB1 inflammatory pathway in hippocampus, and LXRs may serve as a potential therapeutic target for cognitive impairment with anti-inflammation.

Clinical observation on treatment of active rheumatoid arthritis with Chinese herbal medicine / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the efficacy and safety of Chinese drugs for expelling evil-wind, removing dampness, promoting blood circulation and invigorating yin in treating active rheumatoid arthritis (RA).</p><p><b>METHODS</b>Sixty-seven patients with active RA were randomized into 3 groups, the Group A, B and C. They were made coequal in terms of age, sex and condition of disease and treated respectively with basic treatment (non-steroid anti-inflammation drug combined with immune inhibitor) only, basic treatment + small dose prednisone, and basic treatment + Chinese herbal medicine, all for 8 weeks. The efficacy and adverse effects of treatment were analyzed by scoring.</p><p><b>RESULTS</b>The total effective rate was 20.0% (4/20) in Group A, 810% (17/21) in Group B and 85.7% (18/21) in Group C, the latter two were superior to the former one (P <0.01). Before treatment, comparison of disease activity score (DAS) among the three groups showed no significant difference (P > 0.05). After treatment, improvements of Ritchie arthritis index (RAI), number of swollen joint, erythrocyte sedimentation rate (ESR), general health (GH), and DAS were shown in Group B and C (P <0.05), while in Group A, improvement was only shown in GH (P <0.05). The difference of DAS between pre- and post-treatment was 0.25 +/- 0.77 in Group A, 0.87 +/- 0.60 in Group B and 0.92 +/- 0.59 in Group C, showing statistical significance between Group A vs B and A vs C (P = 0.0000). The total accumulative score of adverse reaction was 3.76 +/- 2.72 in Group C, 9.10 +/- 6.01 in Group A and 14.38 +/- 9.36 in Group B, also showing statistical significance among groups (P < 0.05).</p><p><b>CONCLUSION</b>The combination of Chinese and Western medicine for active RA is effective and safe.</p>