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

Abstract

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.

Trehalose Activates CRE-Dependent Transcriptional Signaling in HT22 Mouse Hippocampal Neuronal Cells: A Central Role for PKA Without cAMP Elevation

“…These receptors bind sugars like glucose, sucrose or mannitol and activate, via G-protein-coupling, intracellular second messenger pathways, in taste buds in the tongue mostly the G-protein Gs thereby elevating intracellular cAMP. Interestingly, Tas1R3 knockout mice show profound nervous system failures including altered behavior, memory and social behavior (Martin et al, 2017 ). Our data clearly show no elevation (or reduction) of intracellular cAMP levels after trehalose application.…”

Olfactory, Taste, and Photo Sensory Receptors in Non-sensory Organs: It Just Makes Sense

“…Sweet receptors are present in the hypothalamus (Ren, 2009 ), where hunger is regulated, as well as in the hippocampus, habenula, cortex, and choroid plexus. TAS1R3 knockout mice express reduced dendritic spine density in the hippocampus and cortex and exhibit alterations in learning, memory, and sociability (Martin et al, 2017 ). These results suggest that sweet-taste perception plays a role in CNS neuronal functionality.…”

Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients

“…Moreover, neuroplasticity consists of strengthening the existing nerve pathways and then establishing new connections. Existing, but weaker connections between brain centers undergo activation ( Martin et al, 2017 ). As a result, the defective function can be restored partially or completely, because other cortical or subcortical structures will take over the function of the damaged area.…”