| First Author | Liu LF | Year | 2023 |
| Journal | Neural Regen Res | Volume | 18 |
| Issue | 9 | Pages | 2019-2028 |
| PubMed ID | 36926728 | Mgi Jnum | J:350146 |
| Mgi Id | MGI:7662503 | Doi | 10.4103/1673-5374.366492 |
| Citation | Liu LF, et al. (2023) Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease. Neural Regen Res 18(9):2019-2028 |
| abstractText | Extracellular amyloid beta (Abeta) plaques are main pathological feature of Alzheimer's disease. However, the specific type of neurons that produce Abeta peptides in the initial stage of Alzheimer's disease are unknown. In this study, we found that 5-hydroxytryptamin receptor 3A subunit (HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice (an Alzheimer's disease model) and patients with Alzheimer's disease. To investigate whether HTR3A-positive interneurons are associated with the production of Abeta plaques, we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Abeta plaques in the mouse model. Some amyloid precursor protein-positive or beta-site amyloid precursor protein cleaving enzyme-1-positive neurites near Abeta plaques were co-localized with HTR3A interneurons. These results suggest that HTR3A -positive interneurons may partially contribute to the generation of Abeta peptides. We treated 5.0-5.5-month-old model mice with tropisetron, a HTR3 antagonist, for 8 consecutive weeks. We found that the cognitive deficit of mice was partially reversed, Abeta plaques and neuroinflammation were remarkably reduced, the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice. These findings suggest that HTR3A interneurons partly contribute to generation of Abeta peptide at the initial stage of Alzheimer's disease and inhibiting HTR3 partly reverses the pathological changes of Alzheimer's disease. |
