Loss of Transient Receptor Potential Ankyrin 1 Channel Deregulates Emotion, Learning and Memory, Cognition, and Social Behavior in Mice

Abstract

The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that helps regulate inflammatory pain sensation and nociception and the development of inflammatory diseases. However, the potential role of the TRPA1 channel and the underlying mechanism in brain functions are not fully resolved. In this study, we demonstrated that genetic deletion of the TRPA1 channel in mice or pharmacological inhibition of its activity increased neurite outgrowth. In vivo study in mice provided evidence of the TRPA1 channel as a negative regulator in hippocampal functions; functional ablation of the TRPA1 channel in mice enhanced hippocampal functions, as evidenced by less anxiety-like behavior, and enhanced fear-related or spatial learning and memory, and novel location recognition as well as social interactions. However, the TRPA1 channel appears to be a prerequisite for motor function; functional loss of the TRPA1 channel in mice led to axonal bundle fragmentation, downregulation of myelin basic protein, and decreased mature oligodendrocyte population in the brain, for impaired motor function. The TRPA1 channel may play a crucial role in neuronal development and oligodendrocyte maturation and be a potential regulator in emotion, cognition, learning and memory, and social behavior.

Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice

“…Likewise, another group showed that in TRPA1 receptor gene-deleted mice behavioral deficits and neuroinflammation were less severe in a transgenic mouse model of Alzheimer's disease [24]. The same group also later demonstrated that the loss of TRPA1 is associated with decreased anxiety-like behavior and improved performance in spatial memory and social discrimination tests [25].Based on these prior data we focused on further elucidating the role of TRPA1 receptors in the cuprizone model. In the present study, the effects of cuprizone in the corpus callosum were studied in mGFAP-driven conditional TRPA1 knockout mice.…”

“…Likewise, another group showed that in TRPA1 receptor gene-deleted mice behavioral deficits and neuroinflammation were less severe in a transgenic mouse model of Alzheimer's disease [24]. The same group also later demonstrated that the loss of TRPA1 is associated with decreased anxiety-like behavior and improved performance in spatial memory and social discrimination tests [25].…”

Methyleugenol Potentiates Central Amygdala GABAergic Inhibition and Reduces Anxiety

“…A previous study reported that ME inhibited the voltage-gated sodium Na V 1.7 channels, which underlies its antinociceptive and anesthetic actions (Wang et al, 2015). Additionally, ME is an agonist of the TRPA1 channel (Moon et al, 2015); blockade or genetic ablation of the TRPA1 channel decreases anxietylike behaviors in mice (de Moura et al, 2014;Lee et al, 2017). Therefore, ME activation of TRPA1 channels may increase anxiety-like behaviors in mice.…”

The role of TRP channels in white matter function and ischaemia

“…It is best known as a sensor for environmental irritants and endogenous electrophilic compounds that are formed during oxidative stress [103] and evoke pain, cold, itch and inflammation [104], however it probably also has other undiscovered functions. In support of this assumption, along with decreased responses to peripheral pain models and temperature changes, global TRPA1 knockouts are hyperactive [105], and have sensory dysregulation, cognitive dysfunction, and motor deficits proposed to result from a decrease in myelination [106].…”