TRPA1 involvement in depression- and anxiety-like behaviors in a progressive multiple sclerosis model in mice

Peres, Diulle Spat; Theisen, Maria Carolina; Fialho, Maria Fernanda Pessano; Dalenogare, Diéssica Padilha; Rodrigues, Patrícia; Kudsi, Sabrina Qader; Bernardes, Laura de Barros; Silva, Náthaly Andrighetto Ruviaro da; Lückemeyer, Débora Denardin; Sampaio, Tuane Bazanella; Pereira, Gabriele Cheiran; Mello, Fernanda Kulinski; Ferreira, Juliano; Bochi, Guilherme Vargas; Oliveira, Sara Marchesan; Antoniazzi, Caren Tatiane de David; Trevisan, Gabriela

doi:10.1016/j.brainresbull.2021.07.011

Cited by 22 publications

(17 citation statements)

References 73 publications

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“…Our results revealed a decrease in time in open arms, leading to an increase in the anxiety index. Similar results were observed in this model 9 days post-immunization (Peres et al, 2021).…”

Section: Ta B L Esupporting

confidence: 91%

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS‐EAE)

Rodrigues,

Frare,

Peres

et al. 2024

Journal of Neurochemistry

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Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) generating neuropathic pain and anxiety. Primary progressive MS (PPMS) is the most disabling clinical form, and the patients present an intense neurodegenerative process. In this context, the advanced oxidation protein products (AOPPs) are oxidized compounds and their accumulation in plasma has been related to clinical disability in MS patients. However, the involvement of AOPPs in neuropathic pain‐ and anxiety‐like symptoms was not previously evaluated. To assess this, female mice C57BL/6J were used to induce progressive experimental autoimmune encephalomyelitis (PMS‐EAE). Clinical score, weight, strength of plantar pressure, rotarod test, mechanical allodynia, and cold hypersensitivity were evaluated before induction (baseline) and on days 7th, 10th, and 14th post‐immunization. We assessed nest building, open field, and elevated plus‐maze tests 13 days post‐immunization. Animals were killed at 14 days post‐immunization; then, AOPPs levels, NADPH oxidase, and myeloperoxidase (MPO) activity were measured in the prefrontal cortex, hippocampus, and spinal cord samples. The clinical score increased 14th post‐immunization without changes in weight and mobility. Reduced paw strength, mechanical allodynia, and cold allodynia increased in the PMS‐EAE animals. PMS‐EAE mice showed spontaneous nociception and anxiety‐like behavior. AOPPs concentration, NADPH oxidase, and MPO activity increase in CNS structures. Multivariate analyses indicated that the rise of AOPPs levels, NADPH oxidase, and MPO activity influenced the clinical score and cold allodynia. Thus, we indicated the association between non‐stimuli painful perception, anxiety‐like, and CNS oxidative damage in the PMS‐EAE model.

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Section: Ta B L Esupporting

confidence: 91%

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS‐EAE)

Rodrigues,

Frare,

Peres

et al. 2024

Journal of Neurochemistry

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“…Emerging evidence indicates that TRPA1 is a molecular ionotropic receptor mediator [1] of the neuro-immuno-epithelial interface network [2][3][4] in the lung [5], skin [6] and gut [3,7,8] acting as a "pro-inflammatory hub" [9][10][11]. Absence, dysfunction or inhibition of TRPA1 has been shown to decrease inflammation-related symptoms of psoriasis [6,12,13], rheumatoid arthritis [14], actinic keratosis [15], atopic dermatitis [16][17][18], multiple sclerosis [19][20][21][22][23][24], and its function has been proposed to contribute to a variety of interrelated sensory and inflammatory processes such as inflammatory hyperalgesia [25,26], colitis [7,27], airway inflammation [28,29] and even oxidative stress storm syndromes in COVID-19 [30,31].…”

Section: Introductionmentioning

confidence: 99%

Presence of TRPA1 Modifies CD4+/CD8+ T Lymphocyte Ratio and Activation

et al. 2022

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Transient Receptor Potential Ankyrin 1 (TRPA1) has been reported to influence neuroinflammation and lymphocyte function. We analysed the immune phenotype and activation characteristics of TRPA1-deficient mice (knockout—KO) generated by targeted deletion of the pore-loop domain of the ion channel. We compared TRPA1 mRNA and protein expression in monocyte and lymphocyte subpopulations isolated from primary and secondary lymphatic organs of wild type (WT) and KO mice. qRT-PCR and flow cytometric studies indicated a higher level of TRPA1 in monocytes than in lymphocytes, but both were orders of magnitude lower than in sensory neurons. We found lower CD4+/CD8+ thymocyte ratios, diminished CD4/CD8 rates, and B cell numbers in the KO mice. Early activation marker CD69 was lower in CD4+ T cells of KO, while the level of CD8+/CD25+ cells was higher. In vitro TcR-mediated activation did not result in significant differences in CD69 level between WT and KO splenocytes, but lower cytokine (IL-1β, IL-6, TNF-α, IL-17A, IL-22, and RANTES) secretion was observed in KO splenocytes. Basal intracellular Ca2+ level and TcR-induced Ca2+ signal in T lymphocytes did not differ significantly, but interestingly, imiquimod-induced Ca2+ level in KO thymocytes was higher. Our results support the role of TRPA1 in the regulation of activation, cytokine production, and T and B lymphocytes composition in mice.

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“…We observed impaired cognitive and motor functions with EAE progression, which were assessed using behavioral tests. In this context, the novel object recognition (NOR) test was performed to evaluate the cognitive function on the 11th day where mice with scores > 2 were excluded to prevent the negative interference of motor impairment on the results, consistent with previous studies (Ludwig et al 2017 ; Peres et al 2021 ). Further, open field, rotarod, and grip strength tests were conducted 24 h after the last curcumin administration, including all mice, to assess motor function, coordination, and strength.…”

Section: Methodsmentioning

confidence: 68%

Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway

Sadek,

Rabie,

El Sayed

et al. 2023

Inflammopharmacol

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Multiple sclerosis (MS) is an incurable chronic neurodegenerative disease where autoimmunity, oxidative stress, and neuroinflammation collaboration predispose myelin sheath destruction. Interestingly, curcumin, a natural polyphenol, showed a neuroprotective effect in numerous neurodegenerative diseases, including MS. Nevertheless, the influence of curcumin against MS-induced cognitive impairment is still vague. Hence, we induced experimental autoimmune encephalomyelitis (EAE) in mice using spinal cord homogenate (SCH) and complete Freund’s adjuvant, which eventually mimic MS. This study aimed not only to evaluate curcumin efficacy against EAE-induced cognitive and motor dysfunction, but also to explore a novel mechanism of action, by which curcumin exerts its beneficial effects in MS. Curcumin (200 mg/kg/day) efficacy was evaluated by behavioral tests, histopathological examination, and biochemical tests. Concisely, curcumin amended EAE-induced cognitive and motor impairments, as demonstrated by the behavioral tests and histopathological examination of the hippocampus. Interestingly, curcumin activated the adenosine monophosphate (AMP)-activated protein kinase/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1) axis, which triggered cyclic AMP response element-binding protein/brain-derived neurotrophic factor/myelin basic protein (CREB/BDNF/MBP) pathway, hindering demyelination of the corpus callosum. Furthermore, AMPK/SIRT1 activation augmented nuclear factor erythroid 2-related factor 2 (Nrf2), a powerful antioxidant, amending EAE-induced oxidative stress. Additionally, curcumin abolished EAE-induced neuroinflammation by inhibiting Janus kinase 2 /signal transducers and activators of transcription 3 (JAK2/STAT3) axis, by various pathways, including AMPK/SIRT1 activation. JAK2/STAT3 inhibition halts inflammatory cytokines synthesis. In conclusion, curcumin’s neuroprotective effect in EAE is controlled, at least in part, by AMPK/SIRT1 activation, which ultimately minimizes EAE-induced neuronal demyelination, oxidative stress, and neuroinflammation. Graphical Abstract Graphical illustration of putative molecular pathways implicated in the management of EAE by curcumin. Curcumin activates AMPK/SIRT1, which in turn activates multiple pathways that hinder neurodegeneration, oxidative stress, and neuroinflammation. Moreover, curcumin conquers the inflammatory pathway JAK2/STAT3/NF-kβ.

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TRPA1 involvement in depression- and anxiety-like behaviors in a progressive multiple sclerosis model in mice

Cited by 22 publications

References 73 publications

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS‐EAE)

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS‐EAE)

Presence of TRPA1 Modifies CD4+/CD8+ T Lymphocyte Ratio and Activation

Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway

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