Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice

K. Bölcskei, Gábor Kriszta, Éva Sághy, Maja Payrits, Éva Sipos, Anett Vranesics, Z. Berente, H. Ábrahám, Péter Ács, S. Komoly, E. Pintér

Research output: Contribution to journalArticle

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Abstract

We have recently reported that the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. The aim of the present study was to gather additional data on the role of TRPA1 by investigating the time course of behavioural alterations and morphological changes in cuprizone-treated TRPA1 receptor gene-deficient mice. Demyelination was induced by feeding male wild-type (WT) and TRPA1 gene-deleted (TRPA1 KO) mice with 0.2% cuprizone for 6 weeks. Behavioural tests were performed once per week to follow cuprizone-induced functional changes. Mechanonociceptive thresholds were investigated by a dynamic plantar aesthesiometer and von Frey filaments. Motor performance was assessed by accelerating RotaRod and horizontal grid tests. For the study of spontaneous activity, the open field test was used. The time course of corpus callosum demyelination was also followed weekly by magnetic resonance imaging (MRI). Histological analysis of myelin loss was performed with Luxol Fast Blue (LFB) staining at week 3 and electron microscopy (EM) at week 6. Astrocyte and microglia accumulation at week 3 was assessed by immunohistochemistry (IHC). Cuprizone treatment induced no changes in mechanonociception or motor performance. In the open arena, cuprizone-treated mice spent more time with locomotion, their mean velocity was significantly higher and the distance they travelled was longer than untreated mice. No statistical difference was detected between WT and TRPA1 KO mice in these parameters. On the other hand, significantly increased rearing behaviour was induced in WT mice compared to TRPA1 KO animals. Morphological changes detected with MRI, LFB, IHC and EM analysis revealed reduced damage of the myelin and attenuated accumulation of astrocytes and microglia in cuprizone-treated TRPA1 KO animals, at each examined time point. Our recent data further suggest that inhibition of TRPA1 receptors could be a promising therapeutic approach to limit central nervous system damage in demyelinating diseases.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Neuroimmunology
Volume320
DOIs
Publication statusPublished - Jul 15 2018

Fingerprint

Cuprizone
Ankyrins
Demyelinating Diseases
Microglia
Myelin Sheath
Astrocytes
Electron Microscopy
Immunohistochemistry
Magnetic Resonance Imaging
Corpus Callosum
Oligodendroglia
Locomotion
Genes
Central Nervous System
Electrons
Apoptosis
Staining and Labeling

Keywords

  • Cuprizone
  • Demyelination
  • Electron microscopy
  • Magnetic resonance imaging
  • Open field test
  • TRPA1 receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice. / Bölcskei, K.; Kriszta, Gábor; Sághy, Éva; Payrits, Maja; Sipos, Éva; Vranesics, Anett; Berente, Z.; Ábrahám, H.; Ács, Péter; Komoly, S.; Pintér, E.

In: Journal of Neuroimmunology, Vol. 320, 15.07.2018, p. 1-10.

Research output: Contribution to journalArticle

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AU - Vranesics, Anett

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