Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice

Glutamate excitotoxicity is considered as the etiology of stroke and neurodegenerative diseases, namely, Parkinson’s disease (PD), Alzheimer’s disease (AD), and others. Meanwhile, substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc), a pivotal site in regulating orofacial no...

Full description

Saved in:
Bibliographic Details
Main Authors: Nhung Ha Thuy Le, Seon Ah Park, Yu Mi Kim, Dong Kuk Ahn, Won Jung, Seong Kyu Han
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/np/2553040
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1825199956880785408
author Nhung Ha Thuy Le
Seon Ah Park
Yu Mi Kim
Dong Kuk Ahn
Won Jung
Seong Kyu Han
author_facet Nhung Ha Thuy Le
Seon Ah Park
Yu Mi Kim
Dong Kuk Ahn
Won Jung
Seong Kyu Han
author_sort Nhung Ha Thuy Le
collection DOAJ
description Glutamate excitotoxicity is considered as the etiology of stroke and neurodegenerative diseases, namely, Parkinson’s disease (PD), Alzheimer’s disease (AD), and others. Meanwhile, substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc), a pivotal site in regulating orofacial nociceptive transmission via Aδ and C primary afferent fibers, majorly utilize glutamate as the principal excitatory neurotransmitter. Fucoxanthin (FCX), a carotenoid pigment extracted from brown seaweed, possesses various pharmaceutical properties including neuroprotective effect in multiple neuronal populations. To date, the direct activity of FCX on the SG of the Vc has not been extensively clarified. Consequently, we investigated the effect of FCX on excitatory signaling mediated by ionotropic glutamate receptors (iGluRs), using the patch-clamp technique recorded from SG neurons of the Vc. Here, FCX directly acted on glutamate receptors independent of voltage-gated sodium channel and γ-aminobutyric acid (GABA)A/glycine receptors in the voltage-clamp mode. Specifically, the N-methyl-D-aspartic acid (NMDA)- and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced responses but not the kainic acid receptor (KAR)-mediated response were suppressed by FCX in standard extracellular solution. Additionally, the inhibitory effect of FCX on NMDA currents was repeatable and concentration-dependent. The FCX blockade of NMDA-mediated excitotoxicity was associated with the modulation of Ca2+ response without affecting Na+ ions. The Ca2+-dependent fluorescence intensity of brain slice was reduced in the presence of FCX. Notably, FCX significantly attenuated the spontaneous firing activity of SG neurons. Altogether, these results reveal that FCX may protect SG neurons against glutamate excitotoxicity via primarily regulating Ca2+ response, thereby inhibiting the excitatory signaling induced by NMDA and AMPA receptors (AMPARs).
format Article
id doaj-art-70493b36f5514c38ad6f1d1c80c119af
institution Kabale University
issn 1687-5443
language English
publishDate 2025-01-01
publisher Wiley
record_format Article
series Neural Plasticity
spelling doaj-art-70493b36f5514c38ad6f1d1c80c119af2025-02-08T00:00:05ZengWileyNeural Plasticity1687-54432025-01-01202510.1155/np/2553040Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile MiceNhung Ha Thuy Le0Seon Ah Park1Yu Mi Kim2Dong Kuk Ahn3Won Jung4Seong Kyu Han5Department of Oral PhysiologyDepartment of Oral PhysiologyDepartment of Oral PhysiologyDepartment of Oral PhysiologyDepartment of Oral MedicineDepartment of Oral PhysiologyGlutamate excitotoxicity is considered as the etiology of stroke and neurodegenerative diseases, namely, Parkinson’s disease (PD), Alzheimer’s disease (AD), and others. Meanwhile, substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc), a pivotal site in regulating orofacial nociceptive transmission via Aδ and C primary afferent fibers, majorly utilize glutamate as the principal excitatory neurotransmitter. Fucoxanthin (FCX), a carotenoid pigment extracted from brown seaweed, possesses various pharmaceutical properties including neuroprotective effect in multiple neuronal populations. To date, the direct activity of FCX on the SG of the Vc has not been extensively clarified. Consequently, we investigated the effect of FCX on excitatory signaling mediated by ionotropic glutamate receptors (iGluRs), using the patch-clamp technique recorded from SG neurons of the Vc. Here, FCX directly acted on glutamate receptors independent of voltage-gated sodium channel and γ-aminobutyric acid (GABA)A/glycine receptors in the voltage-clamp mode. Specifically, the N-methyl-D-aspartic acid (NMDA)- and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced responses but not the kainic acid receptor (KAR)-mediated response were suppressed by FCX in standard extracellular solution. Additionally, the inhibitory effect of FCX on NMDA currents was repeatable and concentration-dependent. The FCX blockade of NMDA-mediated excitotoxicity was associated with the modulation of Ca2+ response without affecting Na+ ions. The Ca2+-dependent fluorescence intensity of brain slice was reduced in the presence of FCX. Notably, FCX significantly attenuated the spontaneous firing activity of SG neurons. Altogether, these results reveal that FCX may protect SG neurons against glutamate excitotoxicity via primarily regulating Ca2+ response, thereby inhibiting the excitatory signaling induced by NMDA and AMPA receptors (AMPARs).http://dx.doi.org/10.1155/np/2553040
spellingShingle Nhung Ha Thuy Le
Seon Ah Park
Yu Mi Kim
Dong Kuk Ahn
Won Jung
Seong Kyu Han
Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice
Neural Plasticity
title Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice
title_full Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice
title_fullStr Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice
title_full_unstemmed Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice
title_short Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice
title_sort fucoxanthin inhibits the nmda and ampa receptors through regulating the calcium response on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in juvenile mice
url http://dx.doi.org/10.1155/np/2553040
work_keys_str_mv AT nhunghathuyle fucoxanthininhibitsthenmdaandampareceptorsthroughregulatingthecalciumresponseonsubstantiagelatinosaneuronsofthetrigeminalsubnucleuscaudalisinjuvenilemice
AT seonahpark fucoxanthininhibitsthenmdaandampareceptorsthroughregulatingthecalciumresponseonsubstantiagelatinosaneuronsofthetrigeminalsubnucleuscaudalisinjuvenilemice
AT yumikim fucoxanthininhibitsthenmdaandampareceptorsthroughregulatingthecalciumresponseonsubstantiagelatinosaneuronsofthetrigeminalsubnucleuscaudalisinjuvenilemice
AT dongkukahn fucoxanthininhibitsthenmdaandampareceptorsthroughregulatingthecalciumresponseonsubstantiagelatinosaneuronsofthetrigeminalsubnucleuscaudalisinjuvenilemice
AT wonjung fucoxanthininhibitsthenmdaandampareceptorsthroughregulatingthecalciumresponseonsubstantiagelatinosaneuronsofthetrigeminalsubnucleuscaudalisinjuvenilemice
AT seongkyuhan fucoxanthininhibitsthenmdaandampareceptorsthroughregulatingthecalciumresponseonsubstantiagelatinosaneuronsofthetrigeminalsubnucleuscaudalisinjuvenilemice