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. 2021 Oct:175:1-15.
doi: 10.1016/j.brainresbull.2021.07.011. Epub 2021 Jul 16.

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

Diulle Spat Peres  1 , Maria Carolina Theisen  1 , Maria Fernanda Pessano Fialho  1 , Diéssica Padilha Dalenogare  1 , Patrícia Rodrigues  1 , Sabrina Qader Kudsi  1 , Laura de Barros Bernardes  1 , Náthaly Andrighetto Ruviaro da Silva  1 , Débora Denardin Lückemeyer  2 , Tuane Bazanella Sampaio  1 , Gabriele Cheiran Pereira  1 , Fernanda Kulinski Mello  1 , Juliano Ferreira  2 , Guilherme Vargas Bochi  1 , Sara Marchesan Oliveira  3 , Caren Tatiane de David Antoniazzi  4 , Gabriela Trevisan  5
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Free article

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

Diulle Spat Peres et al. Brain Res Bull. 2021 Oct.
Free article

Abstract

Progressive multiple sclerosis (PMS) is a neurological disease associated with the development of depression and anxiety, but treatments available are unsatisfactory. The transient receptor potential ankyrin 1 (TRPA1) is a cationic channel activated by reactive compounds, and the blockage of this receptor can reduce depression- and anxiety-like behaviors in naive mice. Thus, we investigated the role of TRPA1 in depression- and anxiety-like behaviors in a PMS model in mice. PMS model was induced in C57BL/6 female mice by the experimental autoimmune encephalomyelitis (EAE). Nine days after the PMS-EAE induction, behavioral tests (tail suspension and elevated plus maze tests) were performed to verify the effects of sertraline (positive control), selective TRPA1 antagonist (A-967,079), and antioxidants (α-lipoic acid and apocynin). The prefrontal cortex and hippocampus were collected to evaluate biochemical and inflammatory markers. PMS-EAE induction did not cause locomotor changes but triggered depression- and anxiety-like behaviors, which were reversed by sertraline, A-967,079, α-lipoic acid, or apocynin treatments. The neuroinflammatory markers (AIF1, GFAP, IL-1β, IL-17, and TNF-α) were increased in mice's hippocampus. Moreover, this model did not alter TRPA1 RNA expression levels in the hippocampus but decrease TRPA1 levels in the prefrontal cortex. Moreover, PMS-EAE induced an increase in NADPH oxidase and superoxide dismutase activities and TRPA1 endogenous agonist levels (hydrogen peroxide and 4-hydroxynonenal). TRPA1 plays a fundamental role in depression- and anxiety-like behaviors in a PMS-EAE model; thus, it could be a possible pharmacological target for treating these symptoms in PMS.

Keywords: Antioxidants; Experimental autoimmune encephalomyelitis; Hippocampus; NADPH oxidase; Sertraline; Superoxide dismutase.

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