LACC1 regulates changes in the intestinal flora in a mouse model of inflammatory bowel disease.

BACKGROUND: The aim of this study was to explore the mechanism whereby LACC1 regulates the intestinal flora in a mouse model of inflammatory bowel disease (IBD). METHODS: C57BL/6 and Lacc1-/- mice were used to establish a mouse model of IBD induced by dextran sodium sulfate (DSS). The effects of Lacc1 deletion in mice were evaluated. Changes in the body weight and stool blood were recorded daily. After 7 days of successful modeling, the mice were sacrificed, blood was collected from the eyeballs, the entire colon was dissected and separated, and the length of the colon was measured. RESULTS: Compared with the wild-type (WT) DSS model group, the Lacc1-/- DSS model group showed a significantly higher disease activity index score (P < 0.05), significantly faster weight loss (P < 0.05), and a significantly shorter colon (P < 0.05), indicating that the colonic mucosal tissue was seriously damaged in the Lacc1-/- DSS model group (P < 0.05). Serum IL-1ß, IL-6, TNF-α, and IFN-γ levels were significantly higher in the Lacc1-/- DSS model group than the WT DSS model group. Principal coordinate analysis showed that there were significant microbiome differences between the WT, Lacc1-/-, WT DSS model, and Lacc1-/- DSS model groups (P < 0.05). Linear discriminant analysis effect size analysis showed that under natural conditions, Lacc1-/- mice had significant changes in their intestinal flora compared with control mice (LDA value > 3 or < 3, P < 0.05). CONCLUSIONS: Lacc1 deletion aggravates DSS-induced IBD in mice.

Early active immunization with Aß3-10-KLH vaccine reduces tau phosphorylation in the hippocampus and protects cognition of mice.

Active and passive anti-Aß immunotherapies have successfully been used for the prevention and treatment of Alzheimer's disease animal models. However, clinical use of these immunotherapies is not effective, because the vaccination is administered too late. At 1 month of age, 100 µL of Aß3-10-KLH peptide (vaccine, 2 µg/µL) was subcutaneously injected into the neck of an amyloid precursor protein/presenilin-1/tau transgenic (3×Tg-AD) mouse model. Aß3-10-KLH peptide was re-injected at 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 months of age. Serum levels of Aß antibody were detected by enzyme-linked immunosorbent assay, while spatial learning and memory ability were evaluated by Morris water maze. Immunohistochemistry was used to detect total tau with HT7 and phosphorylated tau with AT8 (phosphorylation sites Ser202 and Thr205) and AT180 (phosphorylation site Thr231) antibodies in the hippocampus. In addition, western blot analysis was used to quantify AT8 and AT180 expression in the hippocampus. The results showed that after vaccine injection, mice produced high levels of Aß antibody, cognitive function was significantly improved, and total tau and phosphorylated tau levels were significantly reduced. These findings suggest that early active immunization with Aß3-10-KLH vaccine can greatly reduce tau phosphorylation, thereby mitigating the cognitive decline of 3×Tg-AD mice. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 103-316) on April 2, 2016.

Assessment of cerebrovascular reserve impairment using the breath-holding index in patients with leukoaraiosis.

Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth People's Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800014421).

Reduction of amyloid beta by Aß3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-ß (Aß) accumulation, neurofibrillary tangles (NFTs) formation and synaptic alterations. Active immunotherapy is regarded as one of the most promising strategies for AD prevention and treatment. In this research, we used APPswe/PS1M146 V/TauP301 L triple transgenic (3×Tg-AD) mice, in which the pathological changes are the most similar to those in AD patients. The Aß 3-10 -keyhole limpet haemocyanin (KLH) vaccine was administered to mice at 1 month, and no AD-associated changes were detected at that time. The vaccine effectively mitigated AD-like pathology and cognitive dysfunction in the 3×Tg-AD mice. Both soluble and insoluble Aß and tau protein in the brain tissues of the 3×Tg-AD mice were significantly decreased after the administration of Aß 3-10 -KLH. In addition, the level of phosphorylated tau also decreased following removal of the Aß pathological changes.