Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices

Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; Coutre, Johannes le; Markram, Henry

doi:10.1038/srep06825

Cited by 33 publications

(30 citation statements)

References 39 publications

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“…Capsaicin also modulates potassium channels and inhibits neuronal action potentials via TRPV1‐independent pathways (Pezzoli et al . ; Yang et al . ) and elicits inward Na + currents in ∼1/4 of geniculate ganglion neurons (Nakamura & Bradley, ) despite the absence of TRPV1 expression in that ganglion (Dvoryanchikov et al .…”

Section: Discussionmentioning

confidence: 99%

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol and mustard oil

Leijon

Neves

Breza

et al. 2019

The Journal of Physiology

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Key points Orosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range. Many of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol, and/or mustard oil (allyl isothiocyanate) at concentrations found in foods and spices. There is significant but incomplete overlap between afferent trigeminal neurons that respond to oral thermal stimulation and to the above chemesthetic compounds. Capsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses. Abstract When consumed with foods, mint, mustard, and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plants – menthol, allyl isothiocyanate (AITC), and capsaicin, respectively – at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for ∼10% of imaged neurons. We categorized them into three distinct classes: cool‐responsive and warm‐responsive thermosensors, and nociceptors (responsive only to temperatures ≥43–45 °C). Menthol, AITC, and capsaicin also elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm‐responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.

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Section: Discussionmentioning

confidence: 99%

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol and mustard oil

Leijon

Neves

Breza

et al. 2019

The Journal of Physiology

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“…In the present work, we investigated the molecular mechanisms of the protection afforded by capsaicin on neuronal ischemic injury. As both morphological and functional studies indicate that TRPV1 is expressed in cortical neurons (Aguiar et al, 2009; de Novellis et al, 2011; Giordano et al, 2012; Goswami et al, 2010; Huang et al, 2015; Mezey et al, 2000; Pezzoli et al, 2014; Roberts et al, 2004; Shirakawa et al, 2008), investigation of the effects of capsaicin on neuronal survival via its direct action on neuronal TRPV1 is worth noting. Our in vivo combined with in vitro data, particularly the data from trpv1 KO mice, provide evidence for the involvement of neuronal TRPV1 in the protective effect of capsaicin on neuronal ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors

Huang

Cheng

Tan

et al. 2017

Experimental Neurology

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Capsaicin, the ingredient responsible for the pungent taste of hot chili peppers, is widely used in the study and management of pain. Recently, its neuroprotective effect has been described in multiple studies. Herein, we investigated the underlying mechanisms for the neuroprotective effect of capsaicin. Direct injection of capsaicin (1 or 3 nmol) into the peri-infarct area reduced the infarct volume and improved neurological behavioral scoring and motor coordination function in the middle cerebral artery occlusion (MCAO)/reperfusion model in rats. The time window of the protective effect of capsaicin was within 1 h after reperfusion, when excitotoxicity is the main reason of cell death. In cultured cortical neurons, administration of capsaicin attenuated glutamate-induced excitotoxic injury. With respect to the mechanisms of the neuroprotective effect of capsaicin, reduced calcium influx after glutamate stimulation was observed following capsaicin pretreatment in cortical neurons. Trpv1 knockout abolished the inhibitory effect of capsaicin on glutamate-induced calcium influx and subsequent neuronal death. Reduced expression of GluN1 and GluN2B, subunits of NMDA receptor, was examined after capsaicin treatment in cortical neurons. In summary, our studies reveal that the neuroprotective effect of capsaicin in cortical neurons is TRPV1-dependent and down-regulation of the expression and function of NMDA receptors contributes to the protection afforded by capsaicin.

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“…For instance, capsaicin, acting through TRPV1, increases intracellular cAMP, activates cGMP-protein kinase G and Ca 2+ /calmodulin-dependent protein kinase II pathways, and inhibits voltage-gated sodium and potassium channels (Liu et al 2001;Liu & Simon, 2003). Capsaicin also modulates potassium channels and inhibits neuronal action potentials via TRPV1-independent pathways (Pezzoli et al 2014;Yang et al 2014) and elicits inward Na + currents in ß1/4 of geniculate ganglion neurons (Nakamura & Bradley, 2011) despite the absence of TRPV1 expression in that ganglion (Dvoryanchikov et al 2017). Further, topical capsaicin (and mustard oil) is well known to produce vasodilatation and increased blood flow (Jancso, 1960;Jancso et al 1967;Helme & McKernan, 1985;Roberts et al 1992), which itself will alter the mucosal temperature and thus indirectly influence thermosensory responses (Wang et al 1995).…”

Section: Pretreatment With Menthol Affects Oral Thermosensory Respomentioning

confidence: 99%

“…Parenthetically, in the present study changes in mucosal temperature were mitigated by constant perfusion with temperature-controlled artificial saliva. Regarding menthol, in addition to being a TRPM8 agonist and a cooling agent, this compound is a positive allosteric modulator of GABA A receptors and inhibits neuronal excitability through TRP-independent pathways, possibly being related to menthol's role as an anaesthetic (Hall et al 2004;Pezzoli et al 2014). The depression of trigeminal thermoresponses, even to cool, by menthol ( Fig.…”

Section: Pretreatment With Menthol Affects Oral Thermosensory Respomentioning

confidence: 99%

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol, and mustard oil

Leijon

Neves

Simon

et al. 2018

Preprint

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Key pointsr Orosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range.r Many of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol, and/or mustard oil (allyl isothiocyanate) at concentrations found in foods and spices.r There is significant but incomplete overlap between afferent trigeminal neurons that respond to oral thermal stimulation and to the above chemesthetic compounds.r Capsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses.Abstract When consumed with foods, mint, mustard, and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plantsmenthol, allyl isothiocyanate (AITC), and capsaicin, respectively -at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for ß10% of imaged neurons. We categorized them into three distinct classes: cool-responsive and warm-responsive thermosensors, and nociceptors (responsive only to temperatures ࣙ43-45°C). Menthol, AITC, and capsaicin also Sara Leijon received her PhD degree at Karolinska Institutet in Stockholm in 2016. During her doctoral studies she used in vitro whole-cell patch-clamp electrophysiology to study the audio-vestibular brainstem. Currently she works as a postdoctoral research associate at the University of Miami. Her career is focused on sensory neurophysiology. She is currently using in vivo functional imaging to study the two sensory ganglia, geniculate and trigeminal, that innervate the orofacial region. Amanda Neves has a MSc degree in Biomedical Engineering and, in 2018, she obtained her PhD at the University of Campinas, Brazil, investigating neuron-glia communication in dorsal root ganglia in relation to inflammatory pain.S. C. M. Leijon and others J Physiol 597.7 elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm-responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.

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Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices

Cited by 33 publications

References 39 publications

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol and mustard oil

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol and mustard oil

Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol, and mustard oil

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