Abstract
Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune neurological disease and is the most common subtype of MS. In addition, it is associated with the development of depression and anxiety. To date, depressive- and anxiety-like behaviours were only studied using models of progressive MS, which causes severe motor alterations. Thus, we sought to standardise the depressive and anxiety-like behaviours in an RRMS model induced by experimental autoimmune encephalomyelitis (RR-EAE) in mice. The RR-EAE model was induced in C57BL/6 female mice using myelin oligodendrocyte glycoprotein (MOG35-55) antigen and Quillaja saponin (Quil A) as an adjuvant. The immunisation of RR-EAE did not induce locomotor alteration but caused relapsing-remitting induction of clinical scores in mice until 35 post-immunization (p.i.). Also, increased levels of tumour necrosis factor alpha (TNF-α), astrocyte marker (GFAP), and microglial markers (IBA-1) were detected in the prefrontal cortex at 35 p.i. of RR-EAE. In the open field test, RR-EAE mice showed decreased time spent at the centre and sniffing behaviour (at days 21 and 34 p.i.). Also, on day 35 p.i. the RR-EAE group spent less time in the open arms and had decreased open-arm entries compared to control mice in the elevated plus maze (EPM) test, confirming the anxiety-like behaviour. At day 36° p.i. in the tail suspension test, mice showed depression-like behaviour with decreased latency time and increased immobility time. Thus, the RR-EAE model mimics the neuroinflammatory and behavioural features of the RRMS, including depression- and anxiety-like symptoms.
Highlights
The RR-EAE model induced depression- and anxiety-like behaviours in mice.
Astrocytic activation marker was increased in the prefrontal cortex of RR-EAE mice.
Microglial marker was increased in the prefrontal cortex of RR-EAE induced mice.
TNF-α levels were increased in the prefrontal cortex of RR-EAE induced mice.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code Availability
Not applicable.
Abbreviations
- ACTB:
-
β-actin
- AU:
-
Arbitrary units
- BDNF:
-
Brain-derived neurotrophic factor
- CNS:
-
Central nervous system
- EAE:
-
Experimental autoimmune encephalomyelitis
- EPM:
-
Elevated plus maze test
- GFAP:
-
Glial fibrillary acidic protein
- HPRT:
-
Hypoxanthine-guanine phosphoribosyltransferase
- IBA-1:
-
Ionized calcium-binding adapter molecule-1
- IL-1β:
-
Interleukin 1 beta
- IL-10:
-
Interleukin 10
- MOG35-55:
-
Myelin oligodendrocyte glycoprotein
- MS:
-
Multiple sclerosis
- PPMS:
-
Primary progressive multiple sclerosis
- Quil A:
-
Quillaja saponin
- RRMS:
-
Relapsing-remitting multiple sclerosis
- SPMS:
-
Secondary progressive multiple sclerosis
- TNF-α:
-
Tumor necrosis factor alpha
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Funding
Fellowships from the Conselho Nacional de Desenvolvimento Científico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) were also acknowledged. Ph.D. fellowship to D.S.P from CAPES [process #23081.052442/2020-36]. G.T is the recipient of a fellowship from CNPq [process #303531/2020-7]. Gabriela Trevisan is a recipient of a research grant from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [process #21/2551-0001935-2].
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DSP and GT participated in experimental protocol design.DSP, PR, FTV, JMF, SQK, and GM contribute to behavior tests and sample collection. DSP performed data analysis.DSP, PR, FTV, JMF, SQK, GM, IRL, GM, MAF, AMS, JF and PCLS, participated in the sample analysis.DSP and GT contributed to the writing of the manuscript.All authors have read the manuscript and approved the final version of the manuscript.
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The study was approved by the Institutional Committee for Animal Care and Use of the Federal University of Santa Maria (UFSM, protocol #2381301120/2020) and followed the national animal experimentation board of control (CONCEA) recommendations. No animals or samples needed to be excluded from the study.
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Peres, D.S., Viero, F.T., Rodrigues, P. et al. Characterization of Depression- and Anxiety-Like Behaviours in a Mouse Model of Relapsing-Remitting Multiple Sclerosis. J Neuroimmune Pharmacol 18, 235–247 (2023). https://doi.org/10.1007/s11481-023-10080-z
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DOI: https://doi.org/10.1007/s11481-023-10080-z