Memantine alleviates cognitive impairment and hippocampal morphology injury in a mouse model of chronic alcohol exposure.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.

[Therapeutic effects of moxibustion on neonatal mice with hypoxia-ischemia brain injury].

Objective: To investigate the effects of moxibustion on the behavioral performance, brain morphological structure of mice with hypoxia-ischemia brain injury and to explore its mechanisms. Methods: One hundred and six ICR mice were randomly divided into three groups, sham group (n=23), model group (n=46) and moxibustion-treated group (n=37). Neonatal hypoxic-ischemia brain injury was induced by ligation of common carotid artery followed by hypoxia (8% oxygen, 100 min), and pups in the moxibustion-treated group were administered suspended moxibustion on the Dazhui points (GV14) at a height of approximately 2 cm over a hairless area of the skin once a day for 4 days (i.e. at 2, 24, 48 and 72 hours after hypoxia-ischemia procedure). Behavioral tests were used to evaluate behavioral performance. HE staining was used to observe brain morphological structure. Western blot was used to detect the expression of SOD2 protein, and spectrophotometry was used to determine the content of MDA in the ipsilateral brain. Results: Mouse pups in sham group showed that the behavioral performance was normal, the brain tissue cells were densely and neatly arranged, the expression of SOD2 and the level of MDA in the brain tissues were normal. Compared with sham group, mouse pups in the HI model group exhibited a significant longer latency to complete the righting reflex, geotaxis reflex, cliff avoidance (P＜0.05) and a marked shorter latency to complete the grip test (P＜0.05); and the HI model group had dramatic brain morphological changes showing missing regions, decreased expression of SOD2 protein (P＜0.05) and increased level of MDA in the brain. Compared with HI model group, mouse pups in the moxibustion-treated group exhibited a significant shorter latency to complete the righting reflex, geotaxis reflex, cliff avoidance test (P＜0.05) and a marked longer latency to complete the grip test (P＜0.05); and the moxibustion-treated group had less brain morphological changes, increased expression of SOD2 protein (P＜0.05) and decreased level of MDA in the brain (P＜0.05) . Conclusion: Moxibustion could improve behavioral performance and attenuate hypoxia-ischemia brain injury, which might be related to increasing the expression of SOD2 protein and decreasing the content of MDA, thus enhancing the anti-oxidative ability.

miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages.

Previous studies have shown that miR-467b plays a central role in the progression of atherosclerosis via regulating LPL expression. However, the regulatory mechanism of miR-467b in regulateing the CE and FC formation is still unclear. Interestingly, computational analysis demonstrated that ACAT1 which converts intracellular FC into the storage form of CE, and ABCA1 which promotes cellular FC efflux may be target gene of miR-467b. Here, we examined whether miR-467b could target ACAT1 and ABCA1, thereby affecting the CE and FC formation in oxLDL-treatment RAW 264.7 cells. We found that miR-467b regulates the CE:FC ratio in oxLDL-treatment RAW 264.7 macrophages, and the luciferase activity of ACAT1 is regulated by the miR-467b, but the luciferase activity of ABCA1 has no effect. Furthermore, our data suggested that miR-467b highly regulates the endogenous levels of ACAT1 expression, thereby affecting the CE formation in oxLDL-treatment RAW 264.7 macrophages. Taken together, our findings demonstrate that ACAT1 is a target gene of miR-467b, and miR-467b regulated the CE and FC formation via directly target the ACAT1 3'UTR.

¹H NMR-based serum metabolic profiling in compensated and decompensated cirrhosis.

AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A ¹H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R²Y of 0.784 and a Q²Y of 0.598. Twelve metabolites, such as pyruvate, phenylalanine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: ¹H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.