Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

Serebrovska, Zoya O.; Xi, Lei; Tumanovska, Lesya V.; Shysh, Angela M.; Goncharov, Sergii V.; Khetsuriani, Michael; Kozak, Taisia O.; Pashevin, Denis A.; Dosenko, Victor E.; Virko, Sergii V.; Kholin, Viktor A.; Grib, Oksana N.; Utko, Natalie A.; Egorov, Egor; Polischuk, Anna O.; Serebrovska, Tetiana V.

doi:10.3390/life12030432

Open AccessArticle

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

by

Zoya O. Serebrovska

^1,*

,

Lei Xi

^2,*

,

Lesya V. Tumanovska

¹,

Angela M. Shysh

¹

,

Sergii V. Goncharov

¹,

Michael Khetsuriani

¹

,

Taisia O. Kozak

¹,

Denis A. Pashevin

¹,

Victor E. Dosenko

¹,

Sergii V. Virko

³,

Viktor A. Kholin

⁴

,

Oksana N. Grib

⁴,

Natalie A. Utko

⁴

,

Egor Egorov

⁵,

Anna O. Polischuk

¹ and

Tetiana V. Serebrovska

^1,†

¹

Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine

²

Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0204, USA

³

Lashkariov Institute of Semiconductor Physics, National Academy of Sciences, 41 Nauki Ave., 03028 Kyiv, Ukraine

⁴

Department of Age Physiology and Pathology of Nervous System, Chebotarev Institute of Gerontology NAMS of Ukraine, 04114 Kyiv, Ukraine

⁵

CELLGYM Technologies GmbH, 14193 Berlin, Germany

^*

Authors to whom correspondence should be addressed.

^†

This work is dedicated to our co-author Tetiana V. Serebrovska, who unfortunately passed away in April 2021 due to COVID-19.

Life 2022, 12(3), 432; https://doi.org/10.3390/life12030432

Submission received: 13 December 2021 / Revised: 11 March 2022 / Accepted: 14 March 2022 / Published: 16 March 2022

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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Abstract

Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% F_IO₂) and 3-min hyperoxia (33% F_IO₂). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aβ expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT.

Keywords: intermittent hypoxia; Alzheimer’s disease; neutrophil extracellular traps; inflammation; hypoxia inducible factor 1; cognitive Impairment

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MDPI and ACS Style

Serebrovska, Z.O.; Xi, L.; Tumanovska, L.V.; Shysh, A.M.; Goncharov, S.V.; Khetsuriani, M.; Kozak, T.O.; Pashevin, D.A.; Dosenko, V.E.; Virko, S.V.; et al. Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment. Life 2022, 12, 432. https://doi.org/10.3390/life12030432

AMA Style

Serebrovska ZO, Xi L, Tumanovska LV, Shysh AM, Goncharov SV, Khetsuriani M, Kozak TO, Pashevin DA, Dosenko VE, Virko SV, et al. Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment. Life. 2022; 12(3):432. https://doi.org/10.3390/life12030432

Chicago/Turabian Style

Serebrovska, Zoya O., Lei Xi, Lesya V. Tumanovska, Angela M. Shysh, Sergii V. Goncharov, Michael Khetsuriani, Taisia O. Kozak, Denis A. Pashevin, Victor E. Dosenko, Sergii V. Virko, and et al. 2022. "Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment" Life 12, no. 3: 432. https://doi.org/10.3390/life12030432

APA Style

Serebrovska, Z. O., Xi, L., Tumanovska, L. V., Shysh, A. M., Goncharov, S. V., Khetsuriani, M., Kozak, T. O., Pashevin, D. A., Dosenko, V. E., Virko, S. V., Kholin, V. A., Grib, O. N., Utko, N. A., Egorov, E., Polischuk, A. O., & Serebrovska, T. V. (2022). Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment. Life, 12(3), 432. https://doi.org/10.3390/life12030432

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Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

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