| First Author | Seok H | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 4414 |
| PubMed ID | 30867485 | Mgi Jnum | J:275624 |
| Mgi Id | MGI:6307707 | Doi | 10.1038/s41598-019-40736-x |
| Citation | Seok H, et al. (2019) Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus. Sci Rep 9(1):4414 |
| abstractText | Amyloid-beta (Abeta) accumulation in the brain is a pathological feature of Alzheimer's disease (AD) and enhancing Abeta clearance is a potential therapeutic strategy. Pioglitazone is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist and is widely used to treat type 2 diabetes. We previously reported that low-dose pioglitazone increased the expression of low-density lipoprotein receptor-related protein 1 (LRP1), which upregulates the clearance of Abeta, using human brain microvascular endothelial cells. We investigated whether low-dose pioglitazone can rescue the pathological phenotype and memory impairment in senescence-accelerated mouse prone-8 (SAMP8) mice by increasing LRP1 levels. SAMP8 mice were treated with vehicle or pioglitazone in dosages of 2 or 5 mg/kg/day for 7 weeks. In the water maze test, 2 mg/kg/day of pioglitazone significantly attenuated the increased escape latency in SAMP8 mice (p = 0.026), while 5 mg/kg/day of treatment did not. Compared with vehicle treatment, the hippocampi of SAMP8 mice with 2 mg/kg/day of pioglitazone exhibited fewer Abeta deposits and reduced Abeta1-40 levels, along with elevated LRP1 expression (p = 0.005). Collectively, our results proposed that a new therapeutic application of the PPAR-gamma agonist for AD treatment should be considered at a lower dose than the conventional dose used to treat diabetes. |
