Altered learning, memory, and social behavior in type 1 taste receptor subunit 3 knock-out mice are associated with neuronal dysfunction

The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor involved in sweet-taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant...

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Published in:The Journal of biological chemistry 2017-07, Vol.292 (27), p.11508-11530
Main Authors: Martin, Bronwen, Wang, Rui, Cong, Wei-Na, Daimon, Caitlin M., Wu, Wells W., Ni, Bin, Becker, Kevin G., Lehrmann, Elin, Wood, William H., Zhang, Yongqing, Etienne, Harmonie, van Gastel, Jaana, Azmi, Abdelkrim, Janssens, Jonathan, Maudsley, Stuart
Format: Article
Language:English
Subjects:
7-helix receptor
Animals
Behavior, Animal
dendritic spine
Dendritic Spines - metabolism
Dendritic Spines - pathology
hippocampus
Learning
Memory
Mice
Mice, Knockout
Neurites - metabolism
Neurites - pathology
Receptors, G-Protein-Coupled - deficiency
Signal Transduction
Social Behavior
synaptic plasticity
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Summary:The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor involved in sweet-taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant metabolic or endocrinological dysfunctions regulated by the sweet-taste perception system, we hypothesized that a disruption of the sweet-taste perception in the brain could have a key role in the development of cognitive dysfunction. To assess the importance of the sweet-taste receptors in the brain, we conducted transcriptomic and proteomic analyses of cortical and hippocampal tissues isolated from T1R3 knock-out (T1R3KO) mice. The effect of an impaired sweet-taste perception system on cognition functions were examined by analyzing synaptic integrity and performing animal behavior on T1R3KO mice. Although T1R3KO mice did not present a metabolically disrupted phenotype, bioinformatic interpretation of the high-dimensionality data indicated a strong neurodegenerative signature associated with significant alterations in pathways involved in neuritogenesis, dendritic growth, and synaptogenesis. Furthermore, a significantly reduced dendritic spine density was observed in T1R3KO mice together with alterations in learning and memory functions as well as sociability deficits. Taken together our data suggest that the sweet-taste receptor system plays an important neurotrophic role in the extralingual central nervous tissue that underpins synaptic function, memory acquisition, and social behavior.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M116.773820