Blocking Microglial Proliferation by CSF-1R Inhibitor Does Not Alter the Neuroprotective Effects of Adoptive Regulatory T Cells in 3xTg Alzheimer's Disease Mice.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes cognitive impairment. Neuroinflammation induced by activated microglia exacerbates AD. Regulatory T cells (Tregs) play roles in limiting neuroinflammation by converting microglial polarization. Therefore, adoptive Treg therapy is considered an attractive option for neurodegenerative disorders. However, the mechanism underlying Treg therapy via microglial modulation is not fully understood. In this study, we sought to determine whether adoptively transferred Tregs were effective when microglia proliferation was inhibited by using GW2580, which is an inhibitor of CSF1R. We found that inhibition of microglial proliferation during Treg transfer did not alter the therapeutic effects of Tregs on cognitive deficits and the accumulation of Aß and pTAU in 3xTg-AD mice. The expression of pro- and anti-inflammatory markers in the hippocampus of 3xTg mice showed that GW2580 did not affect the inhibition of neuroinflammation by Treg transfer. Additionally, adoptively transferred Tregs were commonly detected in the brain on day 7 after transfer and their levels decreased slowly over 100 days. Our findings suggest that adoptively transferred Tregs can survive longer than 100 days in the brain, suppressing microglial activation and thus alleviating AD pathology. The present study provides valuable evidence to support the prolonged efficacy of adoptive Treg therapy in AD.

Anti-Adipogenic and Anti-Obesity Effects of Gongmi Tea and Gongmi So Extract.

The prevalence of obesity has been increasing worldwide, and its pathogenesis is closely related to preadipo-cyte differentiation. Because the presence of obesity increases the risk of chronic disease, it is important to decrease exces-sive body fat accumulation. This study aimed to demonstrate the anti-adipogenesis and anti-obesity effects of gongmi tea and gongmi so extract. The 3T3-L1 preadipocyte cell line was stained with Oil red O, and the expression levels of peroxi-some proliferator-activated receptor-γ (PPARγ), adiponectin, and fatty acid-binding protein 4 (FABP4) were evaluated via Western blot analysis. A mouse model of obesity was developed by feeding C57BL/6 male mice a high-fat diet (HFD). Gongmi tea or gongmi so extract was orally administered at a dose of 200 mg/kg for 6 weeks. The mouse body weight was measured weekly during the study period, and the epididymal adipose tissue weight and blood serum were analyzed at the end of the study period. The gongmi tea and gongmi so extract did not exhibit toxicity in mice. Oil red O staining showed that gongmi tea significantly decreased excessive body fat accumulation. In addition, gongmi tea (300 µg/mL) significantly downregulated adipogenic transcription factors, such as PPARγ, adiponectin, and FABP4. In vivo tests indicated that oral administration of gongmi tea or gongmi so extract to C57BL/6 mice with HFD-induced obesity effectively decreased their body weight and epididymal adipose tissue. Gongmi tea and gongmi so extract have potent in vitro anti-adipogenic effects in 3T3-L1 cells and in vivo anti-obesity effects in mice with HFD-induced obesity.