Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress
by
Maria Antonietta Ajmone-Cat 1,†, Chiara Spinello 2,3,†, Daniela Valenti 4, Francesca Franchi 2, Simone Macrì 2, Rosa Anna Vacca 4,*
and Giovanni Laviola 2,*
Maria Antonietta Ajmone-Cat 1,†, Chiara Spinello 2,3,†, Daniela Valenti 4, Francesca Franchi 2, Simone Macrì 2, Rosa Anna Vacca 4,* and Giovanni Laviola 2,*
1
National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Rome, Italy
2
Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161 Rome, Italy
3
Department of Mechanical and Aerospace Engineering, New York University Tandon School of Engineering, Brooklyn, NY 11201, USA
4
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Via Giovanni Amendola 122/O - 70126 Bari, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(10), 1514; https://doi.org/10.3390/jcm8101514
Received: 9 September 2019 / Revised: 17 September 2019 / Accepted: 18 September 2019 / Published: 20 September 2019
(This article belongs to the Special Issue The Rise of Mitochondria in Medicine)
Adverse psychosocial experiences have been shown to modulate individual responses to immune challenges and affect mitochondrial functions. The aim of this study was to investigate inflammation and immune responses as well as mitochondrial bioenergetics in an experimental model of Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS). Starting in adolescence (postnatal day 28), male SJL/J mice were exposed to five injections (interspaced by two weeks) with Group-A beta-haemolytic streptococcus (GAS) homogenate. Mice were exposed to chronic psychosocial stress, in the form of protracted visual exposure to an aggressive conspecific, for four weeks. Our results indicate that psychosocial stress exacerbated individual response to GAS administrations whereby mice exposed to both treatments exhibited altered cytokine and immune-related enzyme expression in the hippocampus and hypothalamus. Additionally, they showed impaired mitochondrial respiratory chain complexes IV and V, and reduced adenosine triphosphate (ATP) production by mitochondria and ATP content. These brain abnormalities, observed in GAS-Stress mice, were associated with blunted titers of plasma corticosterone. Present data support the hypothesis that challenging environmental conditions, in terms of chronic psychosocial stress, may exacerbate the long-term consequences of exposure to GAS processes through the promotion of central immunomodulatory and oxidative stress.
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Keywords:
PANDAS; adverse emotional experience; immunity; neuroinflammation; animal Models; mitochondrial bioenergetics
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MDPI and ACS Style
Ajmone-Cat, M.A.; Spinello, C.; Valenti, D.; Franchi, F.; Macrì, S.; Vacca, R.A.; Laviola, G. Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress. J. Clin. Med. 2019, 8, 1514.
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