Glioprotective Effects of Resveratrol Against BMAA-Induced Astroglial Dysfunctions.
Astroglial cells
Astroglial dysfunctions
BMAA
Glioprotection
Resveratrol
Journal
Neurotoxicity research
ISSN: 1476-3524
Titre abrégé: Neurotox Res
Pays: United States
ID NLM: 100929017
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
08
02
2022
accepted:
17
03
2022
revised:
13
03
2022
pubmed:
24
3
2022
medline:
27
4
2022
entrez:
23
3
2022
Statut:
ppublish
Résumé
Astroglial cells play important roles in maintaining central nervous system (CNS) homeostasis. The neurotoxin β-N-methylamino-L-alanine (BMAA) has usually been associated with neurodegeneration due to its toxic effects on neurons. However, little is known about the effects of BMAA on astroglial cells. Resveratrol, a natural polyphenol, represents a potential protective strategy against brain injuries. In the present study, we sought to investigate BMAA-induced astroglial dysfunctions and the glioprotective roles of resveratrol. BMAA did not impair astroglial cellular viability, but increased glutamate uptake, glutamate metabolism into glutamine, and reactive oxygen species production, while decreased glutathione (GSH) and superoxide dismutase (SOD)-based antioxidant defenses and triggers an inflammatory response. In contrast, resveratrol was able to prevent most of these BMAA-induced functional changes in astroglial cells. Moreover, both BMAA and resveratrol modulated the gene expression of molecular pathways associated with glutamate metabolism, redox homeostasis, and inflammatory response, which characterize their roles on astroglial functions. In this regard, BMAA downregulated adenosine receptors, peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), phosphoinositide-3-kinase (PI3K), and Akt, while resveratrol prevented these effects and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Our study, for the first time, demonstrates that BMAA directly impacts key astroglial functions, contributing to elucidating the cellular and molecular mechanisms of this toxin in the CNS. In addition, we reinforce the glioprotective effects of resveratrol against BMAA-induced astroglial dysfunctions.
Identifiants
pubmed: 35320508
doi: 10.1007/s12640-022-00492-9
pii: 10.1007/s12640-022-00492-9
doi:
Substances chimiques
Antioxidants
0
Glutamic Acid
3KX376GY7L
Resveratrol
Q369O8926L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
530-541Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Ahmed SMU, Luo L, Namani A et al (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1863:585–597. https://doi.org/10.1016/j.bbadis.2016.11.005
Albano R, Lobner D (2018) Transport of BMAA into neurons and astrocytes by system xc-. Neurotox Res 33:1–5. https://doi.org/10.1007/s12640-017-9739-4
doi: 10.1007/s12640-017-9739-4
pubmed: 28470569
Andersen JV, Markussen KH, Jakobsen E et al (2021) Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. Neuropharmacology 196:108719. https://doi.org/10.1016/j.neuropharm.2021.108719
doi: 10.1016/j.neuropharm.2021.108719
pubmed: 34273389
Argueti-Ostrovsky S, Alfahel L, Kahn J, Israelson A (2021) All roads lead to Rome: different molecular players converge to common toxic pathways in neurodegeneration. Cells 10:2438. https://doi.org/10.3390/cells10092438
doi: 10.3390/cells10092438
pubmed: 34572087
pmcid: 8468417
Arús BA, Souza DG, Bellaver B et al (2017) Resveratrol modulates GSH system in C6 astroglial cells through heme oxygenase 1 pathway. Mol Cell Biochem 428:67–77. https://doi.org/10.1007/s11010-016-2917-5
doi: 10.1007/s11010-016-2917-5
pubmed: 28070834
Bastianetto S, Ménard C, Quirion R (2015) Neuroprotective action of resveratrol. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1852:1195–1201. https://doi.org/10.1016/j.bbadis.2014.09.011
Bellaver B, Bobermin LD, Souza DG et al (2016) Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1862:1827–1838. https://doi.org/10.1016/j.bbadis.2016.06.018
Biasibetti R, Tramontina AC, Costa AP et al (2013) Green tea (−)epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia. Behav Brain Res 236:186–193. https://doi.org/10.1016/j.bbr.2012.08.039
doi: 10.1016/j.bbr.2012.08.039
pubmed: 22964138
Bobermin LD, de Souza Almeida RR, Weber FB et al (2022) Lipopolysaccharide induces gliotoxicity in hippocampal astrocytes from aged rats: insights about the glioprotective roles of resveratrol. Mol Neurobiol. https://doi.org/10.1007/s12035-021-02664-8
doi: 10.1007/s12035-021-02664-8
pubmed: 34993844
Bobermin LD, Quincozes-Santos A, Guerra MC et al (2012) Resveratrol prevents ammonia toxicity in astroglial cells. PLoS ONE 7:e52164. https://doi.org/10.1371/journal.pone.0052164
doi: 10.1371/journal.pone.0052164
pubmed: 23284918
pmcid: 3528750
Bobermin LD, Roppa RHA, Quincozes-Santos A (2019) Adenosine receptors as a new target for resveratrol-mediated glioprotection. Biochim Biophys Acta Mol Basis Dis 1865:634–647. https://doi.org/10.1016/j.bbadis.2019.01.004
doi: 10.1016/j.bbadis.2019.01.004
pubmed: 30611861
Bobermin LD, Souza DO, Gonçalves C-A, Quincozes-Santos A (2013) Lipoic acid protects C6 cells against ammonia exposure through Na+-K+-Cl− co-transporter and PKC pathway. Toxicol in Vitro 27:2041–2048. https://doi.org/10.1016/j.tiv.2013.07.006
doi: 10.1016/j.tiv.2013.07.006
pubmed: 23880158
Bobermin LD, Weber FB, dos Santos TM et al (2020) Sulforaphane induces glioprotection after LPS challenge. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-020-00981-5
doi: 10.1007/s10571-020-00981-5
pubmed: 33079284
Bolaños JP (2016) Bioenergetics and redox adaptations of astrocytes to neuronal activity. J Neurochem 139:115–125. https://doi.org/10.1111/jnc.13486
doi: 10.1111/jnc.13486
pubmed: 26968531
pmcid: 5018236
Browne RW, Armstrong D (1998) Reduced glutathione and glutathione disulfide. Free radical and antioxidant protocols. Humana Press, New Jersey, pp 347–352
doi: 10.1385/0-89603-472-0:347
Caller T, Henegan P, Stommel E (2018) The Potential Role of BMAA in Neurodegeneration. Neurotox Res 33:222–226. https://doi.org/10.1007/s12640-017-9752-7
doi: 10.1007/s12640-017-9752-7
pubmed: 28612294
Chiu AS, Gehringer MM, Braidy N et al (2012) Excitotoxic potential of the cyanotoxin β-methyl-amino-l-alanine (BMAA) in primary human neurons. Toxicon 60:1159–1165. https://doi.org/10.1016/j.toxicon.2012.07.169
doi: 10.1016/j.toxicon.2012.07.169
pubmed: 22885173
Chiu AS, Gehringer MM, Braidy N et al (2013) Gliotoxicity of the cyanotoxin, β-methyl-amino-L-alanine (BMAA). Sci Rep 3:1482. https://doi.org/10.1038/srep01482
doi: 10.1038/srep01482
pubmed: 23508043
pmcid: 3601369
Dai X, Yan X, Wintergerst KA et al (2020) Nrf2: redox and metabolic regulator of stem cell state and function. Trends Mol Med 26:185–200. https://doi.org/10.1016/j.molmed.2019.09.007
doi: 10.1016/j.molmed.2019.09.007
pubmed: 31679988
Dall’Igna OP, Bobermin LD, Souza DO, Quincozes-Santos A (2013) Riluzole increases glutamate uptake by cultured C6 astroglial cells. Int j Dev Neurosci 31:482–486. https://doi.org/10.1016/j.ijdevneu.2013.06.002
doi: 10.1016/j.ijdevneu.2013.06.002
pubmed: 23777615
Davis KE, Straff DJ, Weinstein EA et al (1998) Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. J Neurosci 18:2475–2485. https://doi.org/10.1523/JNEUROSCI.18-07-02475.1998
doi: 10.1523/JNEUROSCI.18-07-02475.1998
pubmed: 9502808
pmcid: 6793087
D’Mello F, Braidy N, Marçal H et al (2017) Cytotoxic effects of environmental toxins on human glial cells. Neurotox Res 31:245–258. https://doi.org/10.1007/s12640-016-9678-5
doi: 10.1007/s12640-016-9678-5
pubmed: 27796937
dos Santos AQ, Nardin P, Funchal C et al (2006) Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells. Arch Biochem Biophys 453:161–167. https://doi.org/10.1016/j.abb.2006.06.025
doi: 10.1016/j.abb.2006.06.025
pubmed: 16904623
Flynn JM, Melov S (2013) SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radical Biol Med 62:4–12. https://doi.org/10.1016/j.freeradbiomed.2013.05.027
doi: 10.1016/j.freeradbiomed.2013.05.027
Gabbouj S, Ryhänen S, Marttinen M et al (2019) Altered insulin signaling in Alzheimer’s disease brain – special emphasis on PI3K-Akt pathway. Front Neurosci 13:629. https://doi.org/10.3389/fnins.2019.00629
doi: 10.3389/fnins.2019.00629
pubmed: 31275108
pmcid: 6591470
Galland F, Seady M, Taday J et al (2019) Astrocyte culture models: molecular and function characterization of primary culture, immortalized astrocytes and C6 glioma cells. Neurochem Int 131:104538. https://doi.org/10.1016/j.neuint.2019.104538
doi: 10.1016/j.neuint.2019.104538
pubmed: 31430518
Gessi S, Merighi S, Stefanelli A et al (2013) A1 and A3 adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes. Pharmacol Res 76:157–170. https://doi.org/10.1016/j.phrs.2013.08.002
doi: 10.1016/j.phrs.2013.08.002
pubmed: 23969284
Gonçalves C-A, Rodrigues L, Bobermin LD et al (2018) Glycolysis-derived compounds from astrocytes that modulate synaptic communication. Front Neurosci 12:1035. https://doi.org/10.3389/fnins.2018.01035
doi: 10.3389/fnins.2018.01035
pubmed: 30728759
Griñán-Ferré C, Bellver-Sanchis A, Izquierdo V et al (2021) The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: from antioxidant to epigenetic therapy. Ageing Res Rev 67:101271. https://doi.org/10.1016/j.arr.2021.101271
doi: 10.1016/j.arr.2021.101271
pubmed: 33571701
Hayes JD, Dinkova-Kostova AT (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39:199–218. https://doi.org/10.1016/j.tibs.2014.02.002
doi: 10.1016/j.tibs.2014.02.002
pubmed: 24647116
Jayakumar AR, Norenberg MD (2016) Glutamine synthetase: role in neurological disorders. Adv Neurobiol 13:327–350. https://doi.org/10.1007/978-3-319-45096-4_13
doi: 10.1007/978-3-319-45096-4_13
pubmed: 27885636
Lissner LJ, Rodrigues L, Wartchow KM et al (2021) Short-term alterations in behavior and astroglial function after intracerebroventricular infusion of methylglyoxal in rats. Neurochem Res 46:183–196. https://doi.org/10.1007/s11064-020-03154-4
doi: 10.1007/s11064-020-03154-4
pubmed: 33095439
Liu X, Rush T, Zapata J, Lobner D (2009) β-N-methylamino-l-alanine induces oxidative stress and glutamate release through action on system Xc−. Exp Neurol 217:429–433. https://doi.org/10.1016/j.expneurol.2009.04.002
doi: 10.1016/j.expneurol.2009.04.002
pubmed: 19374900
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
doi: 10.1006/meth.2001.1262
pubmed: 11846609
Lobner D, Piana PMT, Salous AK, Peoples RW (2007) β-N-methylamino-l-alanine enhances neurotoxicity through multiple mechanisms. Neurobiol Dis 25:360–366. https://doi.org/10.1016/j.nbd.2006.10.002
doi: 10.1016/j.nbd.2006.10.002
pubmed: 17098435
Martinez-Lozada Z, Guillem AM, Robinson MB (2016) Transcriptional regulation of glutamate transporters. In: Advances in pharmacology. Elsevier, pp 103–145
Merighi S, Borea PA, Stefanelli A et al (2015) A2a and a2b adenosine receptors affect HIF-1α signaling in activated primary microglial cells. Glia 63:1933–1952. https://doi.org/10.1002/glia.22861
doi: 10.1002/glia.22861
pubmed: 25980546
Myers TG, Nelson SD (1990) Neuroactive carbamate adducts of beta-N-methylamino-L-alanine and ethylenediamine. Detection and quantitation under physiological conditions by 13C NMR. J Biol Chem 265:10193–10195
doi: 10.1016/S0021-9258(18)86928-9
Pierozan P, Cattani D, Karlsson O (2020a) Hippocampal neural stem cells are more susceptible to the neurotoxin BMAA than primary neurons: effects on apoptosis, cellular differentiation, neurite outgrowth, and DNA methylation. Cell Death Dis 11:910. https://doi.org/10.1038/s41419-020-03093-6
doi: 10.1038/s41419-020-03093-6
pubmed: 33099583
pmcid: 7585576
Pierozan P, Piras E, Brittebo E, Karlsson O (2020b) The cyanobacterial neurotoxin β-N-methylamino-l-alanine (BMAA) targets the olfactory bulb region. Arch Toxicol 94:2799–2808. https://doi.org/10.1007/s00204-020-02775-6
doi: 10.1007/s00204-020-02775-6
pubmed: 32435914
pmcid: 7395073
Proctor EA, Mowrey DD, Dokholyan NV (2019) β-Methylamino-L-alanine substitution of serine in SOD1 suggests a direct role in ALS etiology. PLoS Comput Biol 15:e1007225. https://doi.org/10.1371/journal.pcbi.1007225
doi: 10.1371/journal.pcbi.1007225
pubmed: 31323035
pmcid: 6668853
Quincozes-Santos A, Bobermin LD, de Assis AM et al (2017) Fluctuations in glucose levels induce glial toxicity with glutamatergic, oxidative and inflammatory implications. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1863:1–14. https://doi.org/10.1016/j.bbadis.2016.09.013
Quincozes-Santos A, Bobermin LD, Latini A et al (2013) Resveratrol protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PLoS ONE 8:e64372. https://doi.org/10.1371/journal.pone.0064372
doi: 10.1371/journal.pone.0064372
pubmed: 23691207
pmcid: 3654976
Quincozes-Santos A, Bobermin LD, Souza DG et al (2014) Guanosine protects C6 astroglial cells against azide-induced oxidative damage: a putative role of heme oxygenase 1. J Neurochem 130:61–74. https://doi.org/10.1111/jnc.12694
doi: 10.1111/jnc.12694
pubmed: 24673378
Quincozes-Santos A, Gottfried C (2011) Resveratrol modulates astroglial functions: neuroprotective hypothesis: resveratrol modulates astroglial functions. Ann N Y Acad Sci 1215:72–78. https://doi.org/10.1111/j.1749-6632.2010.05857.x
doi: 10.1111/j.1749-6632.2010.05857.x
pubmed: 21261643
Quincozes-Santos A, Santos CL, de Souza Almeida RR et al (2021) Gliotoxicity and glioprotection: the dual role of glial cells. Mol Neurobiol 58:6577–6592. https://doi.org/10.1007/s12035-021-02574-9
doi: 10.1007/s12035-021-02574-9
pubmed: 34581988
Rakonczay Z, Matsuoka Y, Giacobini E (1991) Effects of L-β-N-methylamino-L-alanine (L-BMAA) on the cortical cholinergic and glutamatergic systems of the rat. J Neurosci Res 29:121–126. https://doi.org/10.1002/jnr.490290114
doi: 10.1002/jnr.490290114
pubmed: 1653366
Robinson MB (2006) Acute regulation of sodium-dependent glutamate transporters: a focus on constitutive and regulated trafficking. In: Sitte HH, Freissmuth M (eds) Neurotransmitter transporters. Springer-Verlag, Berlin/Heidelberg, pp 251–275
doi: 10.1007/3-540-29784-7_13
Silva DF, Candeias E, Esteves AR et al (2020) Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer’s disease features in cortical neurons. J Neuroinflammation 17:332. https://doi.org/10.1186/s12974-020-02004-y
doi: 10.1186/s12974-020-02004-y
pubmed: 33153477
pmcid: 7643281
Sofroniew MV (2020) Astrocyte reactivity: subtypes, states, and functions in CNS innate immunity. Trends Immunol 41:758–770. https://doi.org/10.1016/j.it.2020.07.004
doi: 10.1016/j.it.2020.07.004
pubmed: 32819810
pmcid: 7484257
Takser L, Benachour N, Husk B et al (2016) Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: potential implications for neurodegenerative diseases. Toxicol Rep 3:180–189. https://doi.org/10.1016/j.toxrep.2015.12.008
doi: 10.1016/j.toxrep.2015.12.008
pubmed: 28959538
pmcid: 5615428
Trabelsi Y, Amri M, Becq H et al (2017) The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors: GS Inhibition Reduces EAATs Efficiency. Glia 65:401–415. https://doi.org/10.1002/glia.23099
doi: 10.1002/glia.23099
pubmed: 27862359
Vizuete AFK, de Lima CJ, Neves JD et al (2021) Arundic acid (ONO-2526) inhibits stimulated-S100B secretion in inflammatory conditions. Neurosci Lett 751:135776. https://doi.org/10.1016/j.neulet.2021.135776
doi: 10.1016/j.neulet.2021.135776
pubmed: 33727126
Weiss JH, Choi DW (1988) Beta-N-methylamino-L-alanine neurotoxicity: requirement for bicarbonate as a cofactor. Science 241:973–975. https://doi.org/10.1126/science.3136549
doi: 10.1126/science.3136549
pubmed: 3136549