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Alzheimer's disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients. [ABSTRACT FROM AUTHOR]

Ethanol used by women during pregnancy increases the risk for microtia in the foetus. Traditionally, laboratory experiments and Mouse Genome Informatics (MGI) have been used to explore microtia pathogenesis. The aim of this study was to screen and verify hub genes involved in ethanol-induced microtia and to explore the potential molecular mechanisms. Overlapping genes related to ethanol and microtia were acquired from the GeneCards database and filtered by confidence score. These genes were further analysed via bioinformatics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results were visualized with the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed based on data from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Overall, 41 genes related to both ethanol and microtia were identified. The genes most relevant to ethanol-induced microtia pathogenesis included FGFR-2, FGFR-3, FGF-8, TP53, IGF1, SHH, CTNNB1, and PAX6, among others. Most genes were strongly enriched for tissue and organ development in GO analysis. Additionally, many genes were enriched in the Ras, FoxO, MAPK, and PI3K-Akt signalling pathways in KEGG analysis. Bioinformatics analysis was conducted on genes currently known to be related to ethanol-induced microtia pathogenesis. We propose that mechanisms involving FGF-family genes, TP53, IGF1 and SHH contribute significantly to ethanol-induced microtia and the accompanying malformation of other structures. [ABSTRACT FROM AUTHOR]

• RA patients' depression level correlates with disease activity and quality of life. • Hyperactive LHb drives depression-like behaviors and RA pathology in mice. • Cerebrovascular disruption in LHb associates with depression-like behaviors in RA mice. • Blocking LHb reduces plasma GM-CSF and KC levels, and synovial macrophages. Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression. [ABSTRACT FROM AUTHOR]