Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress
Abstract
:1. Introduction
2. Experimental Section
2.1. Animals and Rearing
2.2. Immunization Protocol
2.3. Chronic Psychosocial Stress
2.4. Experimental Design
2.5. Blood Serum Sampling and Corticosterone Determination
2.6. Analysis of Anti-Group A Streptococcal Antibodies in Serum Samples
2.7. Brain Sampling
2.8. Real-Time Quantitative Polymerase Chain Reaction (RT-PCR)
- HPRT (NM_013556): forward 5′-CAGGCCAGACTTTG-TTGGAT-3′; reverse 5′-TTGCGCTCATC-TTAGGCTTT-3′;
- IL-1β (NM_008361): forward 5′-CGACAAAATACCTGTGGCCT-3′, reverse 5′-TTCTTTGGGTATTCCTTGGG-3′;
- TNF-α (NM_013693.3): forward 5′-AGCCCCCAGTCTGTATCCTT-3′, reverse 5′-ACAGTCCAGGTCACTGTCCC-3′;
- IL-10 (NM_010548): forward 5′-TTAAGCTGTTTCCATTGGGG-3′, reverse 5′-AAGTGTGGCCAGCCTTAGAA-3′;
- iNOS (NM_010927): forward 5′-CAGCTGGGCTGTACAAACCTT-3′, reverse 5′-CATTGGAAGTGAAGCGTTTCG-3′;
- Arg-1 (NM_007482): forward 5′-GGAAAGCCAATGAAGAGCTG-3′, reverse 5′-AACACTCCCCTGACAACCAG-3′;
- MnSOD (NC_000083.6): forward 5′-GCTCTGGCCAAGGGAGATGT-3′, reverse, 5′-GGGCTCAGGTTTGTCCAGAAA-3′;
- GR (NM_008173.3): forward 5′-CGCCAAGTGATTGCCGC-3′, reverse 5′-TGTAGAAGGGTCATTTGGTCATCCA-3′.
2.9. Measurement of Mitochondrial Respiratory Chain Complex (MRC) Activities
2.10. Measurement of Mitochondrial ATP Production Rate
2.11. Measurement of Mouse Brain ATP Levels
2.12. T-Maze
2.13. Statistical Analyses
2.14. Data Statement
3. Results
3.1. Evaluation of Anti-GAS Antibody Responses in Sera from Mice Injected with GAS Homogenates and Exposed (or not) to Chronic Psychosocial Stress
3.2. Consequences of Psychosocial Stress on Serum Corticosterone Concentrations and Glucocorticoid Receptor mRNA Levels in Hypothalamus and Hippocampus
3.3. Behavioural Profile Exhibited during the First Active Social Confrontation
3.4. Chronic Psychosocial Stress Increased Inflammatory Genes Expression in the Brain of GAS Mice
3.5. Psychosocial Stress Affects Mitochondrial OXPHOS Machinery and Reduces Energy Status in the Brain of GAS Immunized Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Behaviour | Parameter | GAS-Stress | PBS-Stress | F (df) | p | Cohen’s d |
---|---|---|---|---|---|---|
Attack received | Duration | 6.559 ± 1.135 | 4.996 ± 0.957 | 3.578 (1,37) | 0.07 Treat × Time ^ | 1.489 |
Frequency | 9.974 ± 1.866 | 7.175 ± 1.422 | 4.338 (1,37) | 0.04 Treat × Time * | 1.687 | |
Defensive upright posture | Duration | 23.724 ± 3.616 | 16.925 ± 3.482 | 1.707 (1,38) | 0.20 | 1.915 |
Frequency | 10.575 ± 1.729 | 6.079 ± 1.076 | 3.545 (1,37) | 0.07 Treat ^ | 3.122 | |
Latency | 212.518 ± 36.059 | 337.022 ± 43.116 | 4.907 (1,38) | 0.03 Treat * | 3.132 | |
Self-grooming | Duration | 13.048 ± 2.366 | 12.784 ± 2.318 | 0.007 (1,38) | 0.93 | 0.113 |
Frequency | 3.350 ± 0.452 | 2.900 ± 0.477 | 0.707 (1,38) | 0.41 | 0.968 | |
Immobility attack-related | Duration | 8.967 ± 2.156 | 2.923 ±.1.181 | 3.279 (1,36) | 0.08 Treat ^ | 3.477 |
Frequency | 3.475 ± 0.791 | 2.350 ± 0.648 | 3.777 (1,38) | 0.06 Treat ^ | 1.556 | |
Immobility contact-related | Duration | 13.3 ± 3.650 | 3.988 ± 1.022 | 5.402 (1,37) | 0.03 Treat * | 3.474 |
Frequency | 2.950 ± 0.636 | 1.447 ± 0.375 | 3.982 (1,37) | 0.05 Treat ^ | 2.879 | |
Submissive behaviours | Duration | 55.198 ± 6.601 | 45.790 ± 7.840 | 0.843 (1,38) | 0.36 | 1.298 |
Frequency | 24.550 ± 3.890 | 17.700 ± 3.069 | 1.911 (1,38) | 0.17 | 1.955 | |
Fleeing | Duration | 7.909 ± 1.452 | 6.480 ± 1.233 | 0.381 (1,37) | 0.54 | 1.061 |
Frequency | 9.650 ± 1.743 | 6.350 ± 1.212 | 1.607 (1,38) | 0.21 | 2.198 | |
Latency | 285.654 ± 39.534 | 349.358 ± 46.590 | 1.087 (1,38) | 0.30 | 1.474 |
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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. https://doi.org/10.3390/jcm8101514
Ajmone-Cat MA, Spinello C, Valenti D, Franchi F, Macrì S, Vacca RA, Laviola G. Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress. Journal of Clinical Medicine. 2019; 8(10):1514. https://doi.org/10.3390/jcm8101514
Chicago/Turabian StyleAjmone-Cat, Maria Antonietta, Chiara Spinello, Daniela Valenti, Francesca Franchi, Simone Macrì, Rosa Anna Vacca, and Giovanni Laviola. 2019. "Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress" Journal of Clinical Medicine 8, no. 10: 1514. https://doi.org/10.3390/jcm8101514