Role of transient receptor potential ankyrin 1 channels in Alzheimer’s disease

Lee, Kuan I.; Lee, Hsueh Te; Lin, Hui Ching; Tsay, Huey Jen; Tsai, Feng Chuan; Shyue, Song Kun; Lee, Tzong‐Shyuan

doi:10.1186/s12974-016-0557-z

Cited by 87 publications

(73 citation statements)

References 66 publications

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“…Other components include menthofuran, 1,8-cineol, terpenoids, and flavonoids such as eriocitrin, hesperidin, and kaempferol 7-O-rutinoside [35]. The main cellular receptor for peppermint odor is transient receptor potential cation channel subfamily A member 1, which is associated with AD [36,37]. Peppermint (Mentha piperita) essential oil, which has high levels of menthol/menthone and characteristic in vitro cholinergic inhibitory, calcium regulatory, and GABAA/nicotinic receptor-binding properties, beneficially modulated performance on demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive task performance in healthy adults [38].…”

Section: Discussionmentioning

confidence: 99%

Inability to Smell Peppermint Is Related to Cognitive Decline: A Prospective Community-Based Study

et al. 2020

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Background: A few studies have demonstrated the association of poorer olfactory identification (OI) with poorer cognition in population-based cohorts. None of them considered the outcome associated with the inability to smell a certain odor. Objective: To verify the hypothesis that at least one specific odor is associated with incident cognitive decline among older adults. Methods: In the Shanghai Aging Study, a sub-cohort of 948 dementia-free participants who had baseline OI measurements were prospectively followed for 5 years. Results: An inability to smell peppermint (β = -0.44, p < 0.001), rose (β = -0.14, p = 0.040), or coffee (β = -0.37, p = 0.002) was inversely related to the annual rate of change in the Mini Mental State Examination score, and an inability to smell peppermint was associated with a higher risk for incident dementia (hazard ratio 2.67, 95% CI 1.44-4.96) after adjustment for confounders. Conclusion: Our study suggests that some odors, especially peppermint, might be considered as a potential predictor for dementia in older populations. Inability to Smell Peppermint and Cognitive Decline

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Section: Discussionmentioning

confidence: 99%

Inability to Smell Peppermint Is Related to Cognitive Decline: A Prospective Community-Based Study

et al. 2020

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“…Since TRPA1 can be triggered by several noxious stimuli, including inflammation, tissue damage or oxidative stress on one hand, and astrocytes influence the extent of this toxin-induced demyelination on the other [29], we assumed that this receptor might modulate the demyelination process. Numerous earlier studies have provided substantial morphological and functional evidence that astrocytes express the TRPA1 receptor, functioning as a regulator of resting Ca 2+ levels [8,9,24,30,31]. In a very recent study, Oh et al, using the cell-type-specific gene-silencing and ultrasensitive sniffer-patch techniques, identified astrocytes as the cellular target and TRPA1 as the molecular sensor for the low intensity, low frequency ultrasound (LILFU).…”

Section: Discussionmentioning

confidence: 99%

“…They detected the functional expression of TRPA1 on oligodendrocytes and showed that ischemia-induced demyelination was diminished in the lack of TRPA1 receptors [11]. 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.…”

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confidence: 99%

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

Kriszta

Nemes

Szepes

et al. 2019

Cells

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Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons; however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice.In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre +/− and floxed TRPA1 (TRPA1 Fl/Fl ) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre +/− TRPA1 Fl/Fl ) and heterozygous (GFAP-Cre +/− TRPA1 Fl/− ) conditional knockout animals compared to Cre −/− control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.Cells 2020, 9, 81 2 of 13 and oxidized lipid molecules [1][2][3]. Apart from being a nocisensor for exogenous irritant compounds, it has been suggested to work as a sensor for oxidative stress [4]. Originally described to be localized on a subgroup of nociceptive primary afferent neurons [5,6], it was later revealed that TRPA1 is also expressed at lower levels by various non-neuronal cells including keratinocytes, endothelial cells and cells of the gastrointestinal mucosa [1-3,7]. More importantly, several studies have supported the presence of TRPA1 receptors in the brain on astrocytes [8][9][10], as well as oligodendrocytes [11]. A recent cell-specific transcriptome analysis of the mouse cortex revealed low level expression of TRPA1 on neurons, astrocytes, oligodendrocytes and microglia, as well [12].In astrocytes, TRPA1 receptors were implicated in both physiological and pathophysiological processes. Astrocyte TRPA1 receptors were shown to regulate resting Ca 2+ levels and modulate GABA-ergic inhibitory transmission by reducing GABA transport [8]. TRPA1 receptors on astrocytes were also suggested to play a role in long-term potentiation in the mouse hippocampus [9]. Since reactive astrocytes can contribute to the progression of neuroinflammation in neurodegenerative diseases [13,14], several workgroups, including ours, had started to investigate the role of TRPA1 in animal models of neurodegenerative diseases. Our previous study aimed at examining the role of TRPA1 in the cuprizone-induced demyelination model in mice. Cuprizone...

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“…Similar to its involvement in other tissues and organs, cortical TRPA1 may contribute to physiological functions such as signal processing in sensory cortex and motor behaviours or in developing pathologies such as in Alzheimer's disease [65], brain oedema or oxidative-stress induced neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

TRPA1 expression and its functional activation in rodent cortex

et al. 2017

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TRPA1 is a non-selective cation channel involved in pain sensation and neurogenic inflammation. Although TRPA1 is well established in a number of organs including the nervous system, its presence and function in the mammalian cortex remains unclear. Here, we demonstrate the expression of TRPA1 in rodent somatosensory cortex through immunostaining and investigate its functional activation by whole-cell electrophysiology, Ca2+ imaging and two-photon photoswitching. Application of TRPA1 agonist (AITC) and antagonist (HC-030031) produced significant modulation of activity in layer 5 (L5) pyramidal neurons in both rats and mice; AITC increased intracellular Ca2+ concentrations and depolarized neurons, and both effects were blocked by HC-030031. These modulations were absent in the TRPA1 knockout mice. Next, we used optovin, a reversible photoactive molecule, to activate TRPA1 in individual L5 neurons of rat cortex. Optical control of activity was established by applying a tightly focused femtosecond-pulsed laser to optovin-loaded neurons. Light application depolarized neurons (n = 17) with the maximal effect observed at λ = 720 nm. Involvement of TRPA1 was further confirmed by repeating the experiment in the presence of HC-030031, which diminished the light modulation. These results demonstrate the presence of TRPA1 in L5 pyramidal neurons and introduce a highly specific approach to further understand its functional significance.

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Role of transient receptor potential ankyrin 1 channels in Alzheimer’s disease

Cited by 87 publications

References 66 publications

Inability to Smell Peppermint Is Related to Cognitive Decline: A Prospective Community-Based Study

Inability to Smell Peppermint Is Related to Cognitive Decline: A Prospective Community-Based Study

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

TRPA1 expression and its functional activation in rodent cortex

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