NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats

被引：3

作者：

Bufan, Biljana ^{[1
]}

Curuvija, Ivana ^{[2
]}

Blagojevic, Veljko ^{[2
]}

Grujic-Milanovic, Jelica ^{[3
]}

Prijic, Ivana ^{[2
]}

Radosavljevic, Tatjana ^{[4
]}

Samardzic, Janko ^{[5
]}

Radosavljevic, Milica ^{[5
]}

Jankovic, Radmila ^{[6
]}

Djuretic, Jasmina ^{[7
]}

机构：

[1] Univ Belgrade, Fac Pharm, Dept Microbiol & Immunol, Belgrade 11000, Serbia

[2] Torlak, Inst Virol Vaccines & Sera, Dept Res & Dev, Belgrade 11000, Serbia

[3] Univ Belgrade, Inst Med Res, Natl Inst Republ Serbia, Dept Cardiovasc Res, Belgrade 11000, Serbia

[4] Univ Belgrade, Inst Pathol Physiol, Fac Med, Belgrade 11000, Serbia

[5] Univ Belgrade, Inst Pharmacol Clin Pharmacol & Toxicol, Fac Med, Belgrade 11000, Serbia

[6] Univ Belgrade, Inst Pathol, Fac Med, Belgrade 11000, Serbia

[7] Univ Belgrade, Fac Pharm, Dept Pathobiol, Belgrade 11000, Serbia

来源：

BIOMEDICINES | 2024年 / 12卷 / 04期

关键词：

aging; NMDARs; memantine; EAE; multiple sclerosis; MULTIPLE-SCLEROSIS; OXIDATIVE STRESS; DAMAGE; BRAIN; INFLAMMATION; DYSFUNCTION; PREVALENCE; TISSUES; SYSTEM; ROLES;

D O I：

10.3390/biomedicines12040717

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes' mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.

引用

页数：18

共 75 条

[1] Role of nitric oxide produced by iNOS through NF-κB pathway in migration of cerebellar granule neurons induced by Lipopolysaccharide [J].

Arias-Salvatierra, Daniela ;

Silbergeld, Ellen K. ;

Acosta-Saavedra, Leonor C. ;

Calderon-Aranda, Emma S. .

CELLULAR SIGNALLING, 2011, 23 (02) :425-435

[2] NMDA Receptors in Immune Competent Cells [J].

Boldyrev, A. A. ;

Bryushkova, E. A. ;

Vladychenskaya, E. A. .

BIOCHEMISTRY-MOSCOW, 2012, 77 (02) :128-134

[3] NRF2 as a Therapeutic Target in Neurodegenerative Diseases [J].

Brandes, Mikah S. ;

Gray, Nora E. .

ASN NEURO, 2020, 12

[4] Late-Onset MS: Disease Course and Safety-Efficacy of DMTS [J].

Buscarinu, Maria Chiara ;

Renie, Roberta ;

Morena, Emanuele ;

Romano, Carmela ;

Bellucci, Gianmarco ;

Marrone, Antonio ;

Bigi, Rachele ;

Salvetti, Marco ;

Ristori, Giovanni .

FRONTIERS IN NEUROLOGY, 2022, 13

[5] CD134 plays a crucial role in the pathogenesis of EAE and is upregulated in the CNS of patients with multiple sclerosis [J].

Carboni, S ;

Aboul-Enein, F ;

Waltzinger, C ;

Killeen, N ;

Lassmann, H ;

Peña-Rossi, C .

JOURNAL OF NEUROIMMUNOLOGY, 2003, 145 (1-2) :1-11

[6] Control of microglial neurotoxicity by the fractalkine receptor [J].

Cardona, Astrid E. ;

Pioro, Erik P. ;

Sasse, Margaret E. ;

Kostenko, Volodymyr ;

Cardona, Sandra M. ;

Dijkstra, Ineke M. ;

Huang, DeRen ;

Kidd, Grahame ;

Dombrowski, Stephen ;

Dutta, RanJan ;

Lee, Jar-Chi ;

Cook, Donald N. ;

Jung, Steffen ;

Lira, Sergio A. ;

Littman, Dan R. ;

Ransohoff, Richard M. .

NATURE NEUROSCIENCE, 2006, 9 (07) :917-924

[7] Role of the Fractalkine Receptor in CNS Autoimmune Inflammation: New Approach Utilizing a Mouse Model Expressing the Human CX3CR11249/M280 Variant [J].

Cardona, Sandra M. ;

Kim, Sangwon V. ;

Church, Kaira A. ;

Torres, Vanessa O. ;

Cleary, Ian A. ;

Mendiola, Andrew S. ;

Saville, Stephen P. ;

Watowich, Stephanie S. ;

Parker-Thornburg, Jan ;

Soto-Ospina, Alejandro ;

Araque, Pedronel ;

Ransohoff, Richard M. ;

Cardona, Astrid E. .

FRONTIERS IN CELLULAR NEUROSCIENCE, 2018, 12

[8] 13 reasons why the brain is susceptible to oxidative stress [J].

Cobley, James Nathan ;

Fiorello, Maria Luisa ;

Bailey, Damian Miles .

REDOX BIOLOGY, 2018, 15 :490-503

[9] The significance of OX40 and OX40L to T-cell biology and immune disease [J].

Croft, Michael ;

So, Takanori ;

Duan, Wei ;

Soroosh, Pejman .

IMMUNOLOGICAL REVIEWS, 2009, 229 :173-191

[10] Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis [J].

Dabrowska-Bouta, Beata ;

Struzynska, Lidia ;

Sidoryk-Wegrzynowicz, Marta ;

Sulkowski, Grzegorz .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (21)

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