| First Author | Sun Z | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 6 | Pages | e13369 |
| PubMed ID | 33960602 | Mgi Jnum | J:333280 |
| Mgi Id | MGI:6718353 | Doi | 10.1111/acel.13369 |
| Citation | Sun Z, et al. (2021) 5-HT6R null mutatrion induces synaptic and cognitive defects. Aging Cell 20(6):e13369 |
| abstractText | Serotonin 6 receptor (5-HT6R) is a promising target for a variety of human diseases, such as Alzheimer's disease (AD) and schizophrenia. However, the detailed mechanism underlying 5-HT6R activity in the central nervous system (CNS) is not fully understood. In the present study, 5-HT6R null mutant (5-HT6R(-/-) ) mice were found to exhibit cognitive deficiencies and abnormal anxiety levels. 5-HT6R is considered to be specifically localized on the primary cilia. We found that the loss of 5-HT6R affected the Sonic Hedgehog signaling pathway in the primary cilia. 5-HT6R(-/-) mice showed remarkable alterations in neuronal morphology, including dendrite complexity and axon initial segment morphology. Neurons lacking 5-HT6R exhibited increased neuronal excitability. Our findings highlight the complexity of 5-HT6R functions in the primary ciliary and neuronal physiology, supporting the theory that this receptor modulates neuronal morphology and transmission, and contributes to cognitive deficits in a variety of human diseases, such as AD, schizophrenia, and ciliopathies. |
