Showing 5-HT6 mutations influenced the distance between the AIS and cell body in hippocampal neurons. Mutations D72A and K265A restored the distance between the AIS and cell body. 5-HT6-EGFP (green) indicated primary cilia. NF186 (purple) was a marker of the AIS. Scale bars, 10 μm. (DOC 6784 kb

Bingjie Wang (767714)

Lili Hu (1833766)

Yan Zhang (8098)

Alzheimer s Research & Therapy

Abstract Background Serotonin receptor 5-HT6 is involved in cognition and Alzheimer’s disease (AD) development. However, the mechanism of 5-HT6 in AD pathology is not clear. Methods Since 5-HT6 is almost exclusively expressed in the primary cilia, using immunostaining we examined the number of cilia in the hippocampus of AD animal model APP/PS1 mice. By overexpressing and knocking down 5-HT6 in the primary cultured hippocampal neurons, we investigated the roles of 5-HT6 in alternating ciliary morphology. Furthermore, 5-HT6 antagonist was applied to confirm its roles in cognition using the Morris water maze test, Y maze, and fear conditioning. Results In the present study, we found that the primary cilia were elongated in the hippocampus of APP/PS1 mice compared with WT mice. 5-HT6 regulated cilia length, influenced cilia and axon initial segment (AIS) morphology, and affected localization of ARL13B and AnkG. We also found that, by changing cilia morphology, the AIS was elongated, branched, and more proximal to the cell body in both WT and APP/PS1 mouse neurons. Alterations of cilia also decreased the axonal length in WT and APP/PS1 neurons. Furthermore, in the water maze test, Y maze, and fear conditioning test, 5-HT6 antagonist SB271046 recovered the cognitive impairment of APP/PS1 mice. Conclusion We suggest that 5-HT6 plays a critical role in AD development through regulating the morphology and function of neuronal primary cilia, which is possibly related to the AIS and axon alterations in AD development

Lili Hu

Bingjie Wang

Yan Zhang

Directory of Open Access Journals

Serotonin 5-HT6 receptors affect cognition in a mouse model of Alzheimer’s disease by regulating cilia function

Augustine, John

Publishing Network for Geoscientific and Environmental Data

Other measurements at 10 m from station Sioux Falls (2015-05)

Background: Serotonin receptor 5-HT6 is involved in cognition and Alzheimer&apos;s disease (AD) development. However, the mechanism of 5-HT6 in AD pathology is not clear.   Methods: Since 5-HT6 is almost exclusively expressed in the primary cilia, using immunostaining we examined the number of cilia in the hippocampus of AD animal model APP/PS1 mice. By overexpressing and knocking down 5-HT6 in the primary cultured hippocampal neurons, we investigated the roles of 5-HT6 in alternating ciliary morphology. Furthermore, 5-HT6 antagonist was applied to confirm its roles in cognition using the Morris water maze test, Y maze, and fear conditioning.   Results: In the present study, we found that the primary cilia were elongated in the hippocampus of APP/PS1 mice compared with WT mice. 5-HT6 regulated cilia length, influenced cilia and axon initial segment (AIS) morphology, and affected localization of ARL13B and AnkG. We also found that, by changing cilia morphology, the AIS was elongated, branched, and more proximal to the cell body in both WT and APP/PS1 mouse neurons. Alterations of cilia also decreased the axonal length in WT and APP/PS1 neurons. Furthermore, in the water maze test, Y maze, and fear conditioning test, 5-HT6 antagonist SB271046 recovered the cognitive impairment of APP/PS1 mice.   Conclusion: We suggest that 5-HT6 plays a critical role in AD development through regulating the morphology and function of neuronal primary cilia, which is possibly related to the AIS and axon alterations in AD development.National Science Foundation of China (NSFC) Fund for Distinguished Young   Scholars [81425009]; NSFC major research grants [31630028, 91632305]SCI(E)ARTICLE

Hu, Lili

Wang, Bingjie

Zhang, Yan

Institutional Repository of Peking University

Serotonin 5-HT6 receptors affect cognition in a mouse model of   Alzheimer&apos;s disease by regulating cilia function

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Additional file 7: Figure S7. of Serotonin 5-HT6 receptors affect cognition in a mouse model of Alzheimer’s disease by regulating cilia function

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Other measurements at 10 m from station Sioux Falls (2015-05)

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Institutional Repository of Peking University

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