Open Access5‐HT6R null mutatrion induces synaptic and cognitive defects
Author(s) -
Sun Zehui,
Wang Bingjie,
Chen Chen,
Li Chenjian,
Zhang Yan
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13369
Subject(s) - biology
Abstract 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.