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

BACKGROUND
Serotonin 5-HT6 receptor is involved in cognition and Alzheimer's disease (AD) development. However, the mechanism of 5-HT6 in the pathology of AD is unclear.
METHOD
Since the 5-HT6 almost exclusively expressed in primary cilia, using Human Clia Kits immunostaining we examine the number of cilia in an animal model of AD hippocampus of APP / PS1 mice. By expressing and knocking down 5-HT6 in primary cultured hippocampal neurons, we investigated the role of 5-HT6 in alternating cilia morphology. Furthermore, 5-HT6 antagonists are applied to confirm its role in cognition using the Morris water maze test, Y maze and fear conditioning.
RESULTS
In this study, we found that primary cilia extending in the hippocampus of APP / PS1 mice compared with WT mice. 5-HT6 long set of cilia, cilia affected and axon initial segment (AIS) morphology and localization of affected ARL13B and AnkG. We also found that, by changing the morphology of cilia, AIS was elongated, branched, and more proximal body cells in both WT and APP / PS1 mice neurons. Changes long cilia also decreased axonal neurons in WT and APP / PS1. Further, in the water maze test, Y maze and fear conditioning test, the 5-HT6 antagonist SB271046 recover cognitive decline APP / PS1 mice.
CONCLUSION
We suggest that the 5-HT6 plays an important role in the development of AD through a set of primary cilia morphology and function of neurons, which may be associated with AIS and axon changes in the development of AD.
Serotonin 5-HT6 receptors affect cognition in a mouse model of Alzheimer's disease by regulating cilia function.

Quantitative Comparison of Primary Cilia and Long Marker Expression in Mouse Brain.



Primary cilia are small, special cell organelles that provide sensory functions and an important signal for mammalian organ development and coordination of cellular processes postnatally. Primary cilia dysfunction is thought to be the main cause ciliopathies, a group of genetic disorders characterized by overlapping developmental disabilities and neurodevelopmental features that stand out. Although, impaired cilia-linked signaling pathways have been involved in the regulation of a variety of nerve function, the exact role of primary cilia in brain is still unknown. 

Importantly, last year's study has highlighted that the Ovine Clia Kits different functions of primary cilia morphology reflected the diverse and unique signaling components are localized in the ciliary membrane. In this study, we performed a comparative analysis of expression patterns, distribution and length of adenylyl cyclase 3 somatostatin receptor 3, and ADP-ribosylation factor-like protein 13B revealed primary cilia in the rat brain. We show that ciliary neurons and astrocytes displaying marked distribution and regulation of cilia marker
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