Peripheral molecular messages – cytokines and stress hormones – in the context of cognitive aging phenotypes: healthy ageing/depression/dementia
- Authors: Burmistrova A.L.1, Cazaux M.E.1, Alekseeva A.S.1, Filippova Y.Y.1
-
Affiliations:
- Chelyabinsk State University
- Issue: Vol 24, No 4 (2021)
- Pages: 461-468
- Section: SHORT COMMUNICATIONS
- Submitted: 21.07.2021
- Accepted: 20.08.2021
- Published: 15.10.2021
- URL: https://rusimmun.ru/jour/article/view/1061
- DOI: https://doi.org/10.46235/1028-7221-1061-PMM
- ID: 1061
Cite item
Full Text
Abstract
Over last years, the world’s aging populations are rising rapidly, and the phenotypes of cognitive insufficiency, such as old age, depression and dementia, are increasing. Search for approaches to discrimination between such phenotypes is extremely relevant. Current studies present compelling evidence of the key role of immune system (its peripheral compartment), and the stress response system in physiological brain health. Therefore, assessment of complex interactions between immune and neuroendocrine systems may be an effective way to differentiate between depression and early stages of dementia in elderly people. Our purpose was to reveal peripheral molecular messages, e.g., cytokines and stress hormones, in the context of cognitive impairment phenotypes: healthy old age/old age depression/dementia. Eighty elderly people were included into groups as follows: “Healthy ageing”, “Dementia”, “Depression”. Levels of certain cytokines: IL-6, IL-1β, TNFα, IFNγ, IL-10, and stress hormones (cortisol, ACTH, dopamine, noradrenaline, and adrenaline) were determined in blood plasma by ELISA. The intergroup differences were evaluated by the Kruskal-Wallis test with Conover-Inman post-hoc pairwise comparisons. For differential diagnostics between the groups of elderly people with varying grades of cognitive impairment, we used linear canonical discriminant analysis performed on the ranks. It has been shown that cognitive insufficiency phenotypes—old age depression and dementia—differ from the healthy ageing phenotype with their high peripheral levels of TNFα cytokine and low levels of IL-1β. The differences between depression in elderly and dementia included lower level of IL-10 in depression (lower than in “Healthy ageing”), and high IL-6 in dementia (compared to “Healthy ageing”). Evaluation of the hypothalamic-pituitary and sympatho-adreno-medullary axes hormones showed hyporesponsiveness of hypothalamic-pituitary axis, regardless of cognitive insufficiency phenotypes, along with activation of sympatho-adreno-medullary axis, i.e., high dopamine level in old age depression with dementia, and high adrenaline level in dementia, than in depression of elderly phenotype and healthy ageing. Such significant differences in the levels of molecular messages, i.e., cytokines and stress hormones among the old age person groups, enabled diagnostic efficacy of 87.5% to differentiate cognitive phenotypes of aging: healthy ageing, old age depression, and dementia.
About the authors
A. L. Burmistrova
Chelyabinsk State University
Email: burmal@csu.ru
ORCID iD: 0000-0001-6462-9500
PhD, MD (Medicine), Professor, Head, Department of Microbiology, Immunology and General Biology, Faculty of Biology
454001, Russian Federation, Chelyabinsk, Bratiev Kashirinykh str., 129
M. E. Cazaux
Chelyabinsk State University
Author for correspondence.
Email: kholodilina@yandex.ru
ORCID iD: 0000-0001-5683-0597
Postgraduate Student, Department of Microbiology, Immunology and General Biology, Faculty of Biology
454001, Russian Federation, Chelyabinsk, Bratiev Kashirinykh str., 129
Phone: 7 (919) 402-11-20
Russian FederationA. S. Alekseeva
Chelyabinsk State University
Email: 96_anya@gmail.com
ORCID iD: 0000-0002-2524-8569
Postgraduate Student, Department of Microbiology, Immunology and General Biology, Faculty of Biology
454001, Russian Federation, Chelyabinsk, Bratiev Kashirinykh str., 129
Russian FederationYu. Yu. Filippova
Chelyabinsk State University
Email: julse@rambler.ru
ORCID iD: 0000-0001-5041-6440
PhD (Biology), Associate Professor, Department of Microbiology, Immunology and General Biology, Faculty of Biology
454001, Russian Federation, Chelyabinsk, Bratiev Kashirinykh str., 129
Russian FederationReferences
- Byers A.L., Yaffe K. Depression and risk of developing dementia. Nat. Rev. Neurol., 2011, vol. 7, no.6, pp. 323-31.
- Franceschi C., Garagnani P., Vitale G., Capri M., Salvioli S. Inflammaging and 'Garb-aging'. Trends Endocrinol. Metab., 2017, vol. 28, no.3, pp. 199-212.
- Fulop T., Larbi A., Dupuis G., Le Page A., Frost E.H., Cohen A.A., Witkowski J.M., Franceschi C. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? Front. Immunol. 2018, vol.8, pp.1960.
- Gupta D., Morley J.E. Hypothalamic-pituitary-adrenal (HPA) axis and aging. Compr. Physiol., 2014 vol.4, no.4, pp. 1495-510.
- Harada C.N., Natelson Love M.C., Triebel K.L. Normal cognitive aging. Clin. Geriatr. Med., 2013, vol. 29, no. 4, pp. 737-752.
- Kipnis J., Gadani S., Derecki N.C. Pro-cognitive properties of T cells. Nat. Rev. Immunol. 2012, vol. 12, no. 9, pp. 663-669.
- Krabbe K.S., Pedersen M., Bruunsgaard H. Inflammatory mediators in the elderly. Exp. Gerontol., 2004, vol. 39, no. 5, pp. 687-699.
- McHugh D., Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J. Cell Biol. 2018, vol. 217, no. 1, pp. 65-77.
- McKenna F., McLaughlin P.J., Lewis B.J., Sibbring G.C., Cummerson J.A., Bowen-Jones D., Moots R.J. Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: a flow cytometric study. J. Neuroimmunol., 2002, vol. 132, no. 1-2, pp.34-40.
- Plassman B.L., Langa K.M., McCammon R.J., Fisher G.G., Potter G.G., Burke J.R., Steffens D.C., Foster N.L., Giordani B., Unverzagt F.W., Welsh-Bohmer K.A., Heeringa S.G., Weir D.R., Wallace R.B. Incidence of dementia and cognitive impairment, not dementia in the United States. Ann Neurol., 2011, vol. 70, no. 3, pp. 418-426.
- Ruan L., Zhang X., Li R. Recent insights into the cellular and molecular determinants of aging. J. Cell Sci. 2018, vol.131, no.3, pp. jcs210831.
- Sapolsky R.M. Doubled-Edged Swords in the Biology of Conflict. Front. Psychol., 2018, vol.9, pp.2625.
- Vallejo A.N., Mueller R.G., Hamel D.L. Jr., Way A., Dvergsten J.A., Griffin P., Newman A.B. Expansions of NK-like αβT cells with chronologic aging: novel lymphocyte effectors that compensate for functional deficits of conventional NK cells and T cells. Ageing Res. Rev., 2011, vol. 10, no. 3, pp. 354-61.
- Vitlic A., Lord J.M., Phillips A.C. Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system. Age (Dordr), 2014, vol. 36, no. 3, pp. 9631.
- Yirmiya R., Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav. Immun., 2011, Vol. 25, no. 2, pp. 181-213.