A mouse model of Chronic Psychosocial Stress: Energetics, Obesity, Psychpathologies and Aging
We developed a unique ethological model of chronic social stress in mice and established a social-rank-dependent vulnerability to psychopathogies and neurological abnormalities. We demonstrated that subordinate mice (low social rank, a model of low socio-economic status) manifest a complex syndrome characterized by a depression-like behavior, increased anxiety, neuroimmune, neuroendocrine and cardiovascular abnormalities (including hypertension). After having characterized the stress-induced neurobehavioral and endocrine pathophysiology we directed our experimental effort to the impact of stress on metabolic functions, feeding behavior, obesity and vulnerability to type 2 diabetes as well as molecular markers of Alzheimer`s disease. Importantly, lifelong social subordination anticipates the onset of many aging-related diseases, increases molecular markers of cellular senescence and causes epigenetic changes consistent with accelerated biological age. Finally, we also demonstrated that chronic social stress is a major risk factor to precipitate genetic diseases in mouse models such as the mdx mouse model of Duchenne Muscular Dystrophy.
Relevant publications
The mouse Social Frailty Index (mSFI): a novel behavioral assessment for impaired social functioning in aging mice. Collinge CW, Razzoli M, Mansk R, McGonigle S, Lamming DW, Pacak CA, van der Pluijm I, Niedernhofer L, Bartolomucci A. Geroscience. 2024 Jul 11. doi: 10.1007/s11357-024-01263-4. Epub ahead of print. PMID: 38987495.
The fortunes and misfortunes of social life across the life course: A new era of research from field, laboratory and comparative studies. Bartolomucci A, Tung J, Harris KM. Neurosci Biobehav Rev. 2024 Jul;162:105655. doi:
10.1016/j.neubiorev.2024.105655. Epub 2024 Apr 5. PMID: 38583652.
Chronic Social and Psychological Stress Impact Select Neuropathologies in the PS19 Mouse Model of Tauopathy. Lyons CE, Graves SI, Razzoli M, Jeganathan K, Mansk RP, McGonigle S, Sabarinathan N, van Deursen JM, Baker DJ, Bartolomucci A. Psychosom Med. 2024 Jun 1;86(5):366-378. doi:
10.1097/PSY.0000000000001256. Epub 2023 Oct 3. PMID: 37910129; PMCID:
PMC10987396.
Retention of stress susceptibility in the mdx mouse model of
Duchenne muscular dystrophy after PGC-1α overexpression or ablation of IDO1 or CD38. Johnson EE, Southern WM, Doud B, Steiger B, Razzoli M, Bartolomucci A, Ervasti JM. Hum Mol Genet. 2024 Mar 20;33(7):594-611. doi: 10.1093/hmg/ddad206. PMID: 38181046; PMCID: PMC10954366.
The impact of life stress on hallmarks of aging and accelerated senescence: Connections in sickness and in health. Lyons CE, Razzoli M, Bartolomucci A. Neurosci Biobehav Rev. 2023 Oct;153:105359. doi: 10.1016/j.neubiorev.2023.105359. Epub 2023 Aug 15. PMID: 37586578; PMCID:PMC10592082.
Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress. Razzoli M, Nyuyki-Dufe K, Chen BH, Bartolomucci A. Proc
Natl Acad Sci U S A. 2023 Apr 18;120(16):e2211755120. doi:
10.1073/pnas.2211755120. Epub 2023 Apr 12. PMID: 37043532; PMCID: PMC10120026.
The multiple roles of life stress in metabolic disorders. Kivimäki M, Bartolomucci A, Kawachi I. Nat Rev Endocrinol. 2023 Jan;19(1):10-27. doi:
10.1038/s41574-022-00746-8. Epub 2022 Oct 12. PMID: 36224493; PMCID:
PMC10817208.
Lifelong chronic psychosocial stress induces a proteomic signature of
Alzheimer's disease in wildtype mice. Lyons CE, Zhou X, Razzoli M, Chen M, Xia W, Ashe K, Zhang B, Bartolomucci A. Eur J Neurosci. 2022
May;55(9-10):2971-2985. doi: 10.1111/ejn.15329. Epub 2021 Jun 22. PMID:
34048087.
Juvenile exposure to doxorubicin alters the cardiovascular response to adult-onset psychosocial stress in mice. Grant MKO, Razzoli M, Abdelgawad IY, Mansk R, Seelig D, Bartolomucci A, Zordoky BN. Stress. 2022 Jan;25(1):291-304. doi: 10.1080/10253890.2022.2104121. PMID: 35942624; PMCID: PMC9749214.
Some dystrophy phenotypes of dystrophin-deficient mdx mice are exacerbated by mild, repetitive daily stress. Lindsay A, Holm J, Razzoli M, Bartolomucci A, Ervasti JM, Lowe DA.FASEB J. 2021 Apr;35(4):e21489. doi:
10.1096/fj.202002500R. PMID: 33734502.
Stress and Alzheimer's disease: A senescence link? Lyons CE, Bartolomucci A.
Neurosci Biobehav Rev. 2020 Aug;115:285-298. doi:
10.1016/j.neubiorev.2020.05.010. Epub 2020 May 24. PMID: 32461080; PMCID:PMC7483955.
Social stress is lethal in the mdx model of Duchenne muscular dystrophy. Razzoli M, Lindsay A, Law ML, Chamberlain CM, Southern WM, Berg M, Osborn J, Engeland WC, Metzger JM, Ervasti JM, Bartolomucci A.EBioMedicine. 2020 May;55:102700. doi: 10.1016/j.ebiom.2020.102700. Epub 2020 Mar 16. PMID: 32192914; PMCID:PMC7251247.
Social stress shortens lifespan in mice. Razzoli M, Nyuyki-Dufe K, Gurney A, Erickson C, McCallum J, Spielman N, Marzullo M, Patricelli J, Kurata M, Pope EA, Touma C, Palme R, Largaespada DA, Allison DB, Bartolomucci A. Aging Cell. 2018 Aug;17(4):e12778. doi: 10.1111/acel.12778. Epub 2018 May 28. PMID:29806171; PMCID: PMC6052478.
Stress, overeating, and obesity: Insights from human studies and preclinical models. Razzoli M, Pearson C, Crow S, Bartolomucci A. Neurosci Biobehav
Rev. 2017 May;76(Pt A):154-162. doi: 10.1016/j.neubiorev.2017.01.026. Epub 2017 Mar 11. PMID: 28292531; PMCID: PMC5403578.
The Dichotomous Effect of Chronic Stress on Obesity. Razzoli M, Bartolomucci A. Trends Endocrinol Metab. 2016 Jul;27(7):504-515. doi:
10.1016/j.tem.2016.04.007. Epub 2016 May 5. PMID: 27162125; PMCID: PMC4912918.
Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. Razzoli M, Frontini A, Gurney A, Mondini E, Cubuk C, Katz LS, Cero C, Bolan PJ, Dopazo J, Vidal-Puig A, Cinti S, Bartolomucci A. Mol Metab. 2015 Nov 11;5(1):19-33. doi:
10.1016/j.molmet.2015.10.005. PMID: 26844204; PMCID: PMC4703853.
Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice. Razzoli M, McCallum J, Gurney A, Engeland WC, Bartolomucci A. Genes Nutr. 2015 May;10(3):458. doi: 10.1007/s12263-015-0458-2. Epub 2015 Mar 20.PMID: 25791744; PMCID: PMC4366428.
Chronic subordination stress induces
hyperphagia and disrupts eating behavior in mice modeling binge-eating-like
disorder. Razzoli M, Sanghez V, Bartolomucci A. Front Nutr. 2015;1(30):30. doi: 10.3389/fnut.2014.00030. PMID: 25621284; PMCID: PMC4300527.