Acute Intermittent Hypoxia Therapy alters cognitive behavioral parameters in wistar albino rats
Abstract
Cognitive disorders, including dementia and Alzheimer's disease, pose substantial global health challenges, demanding effective prevention and treatment strategies. Intermittent Hypoxia Therapy (IHT), involving brief exposures to reduced oxygen levels, is a novel approach with potential cognitive benefits. This study investigates the effects of Intermittent Hypoxia Therapy (IHT) on cognitive behavior in Wistar albino rats through comprehensive behavioral experiments, including the Open Field Test (OFT) and Morris Water Maze (MWM). The results reveal that IHT promotes locomotor activity, reduces anxiety-related behaviors, and positively impacts cognitive flexibility. In the OFT, the IH group exhibited increased grid crossings and distance traveled, indicating heightened locomotion, which may be associated with cognitive improvement. Furthermore, IH significantly reduced thigmotaxis behavior and the number of fecal boli, indicating reduced anxiety levels compared to the control group. While IHT did not significantly enhance spatial memory acquisition in the MWM, it improved platform recognition during the probe test. The IH group spent more time in the target quadrant, suggesting enhanced memory retrieval and recognition. Additionally, in the reverse MWM, IH demonstrated moderate improvements in cognitive flexibility, with faster latency on trial 1. These findings suggest that IHT holds promise as a non-invasive intervention for cognitive enhancement, particularly in terms of locomotor activity, anxiety reduction, and certain aspects of memory and cognitive flexibility. Further research is warranted to elucidate the underlying mechanisms and explore the potential therapeutic applications of IHT in cognitive disorders. In summary, this study highlights the cognitive benefits of IHT in rats, paving the way for future investigations and potential clinical applications in the realm of cognitive disorders.
Keywords:
Cognition, Exercise, Intermittent Hypoxia, Morris Water Maze, Open Field TestDOI
https://doi.org/10.25004/IJPSDR.2023.150512References
Bell MA, Wolfe CD. Emotion and Cognition: An Intricately Bound Developmental Process. Child Development. 2004;75(2):366–70. Available from: https://doi.org/10.1111/j.1467-8624.2004.00679.x
Caruso G, Godos J, Privitera A, Lanza G, Castellano S, Chillemi A, et al. Phenolic Acids and Prevention of Cognitive Decline: Polyphenols with a Neuroprotective Role in Cognitive Disorders and Alzheimer’s Disease. Nutrients. 2022 Feb 15;14(4):819. Available from: https:// doi.org/10.3390/nu14040819
Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimers Dement. 2023 Feb;19(2):658–70. Available from: https://doi.org/10.1002/alz.12694
Erickson KI, Donofry SD, Sewell KR, Brown BM, Stillman CM. Cognitive Aging and the Promise of Physical Activity. Annu Rev Clin Psychol. 2022 May 9;18:417–42. Available from: https://doi. org/10.1146/annurev-clinpsy-072720-014213
Abdivalievna AN, Rahmonkul qizi BH. Features Of Cognitive Disorders. Innovative Society: Problems, Analysis and Development Prospects. 2022 Feb. 17,;:101-5. Available from: https://www. openconference.us/index.php/ISPADP/article/view/177
Behrendt T, Bielitzki R, Behrens M, Herold F, Schega L. Effects of Intermittent Hypoxia–Hyperoxia on Performance- and Health- Related Outcomes in Humans: A Systematic Review. Sports Medicine - Open. 2022 May 31;8(1):70. Available from: https://doi. org/10.1186/s40798-022-00450-x
Dale EA, Ben Mabrouk F, Mitchell GS. Unexpected Benefits of Intermittent Hypoxia: Enhanced Respiratory and Nonrespiratory Motor Function. Physiology. 2014 Jan;29(1):39–48. Available from: https://doi.org/10.1152/physiol.00012.2013
Payne RS, Goldbart A, Gozal D, Schurr A. Effect of intermittent hypoxia on long-term potentiation in rat hippocampal slices. Brain Research. 2004 Dec 17 ;1029(2):195–9. Available from: https://doi. org/10.1016/j.brainres.2004.09.045
Christiansen L, Urbin M, Mitchell GS, Perez MA. Acute intermittent hypoxia enhances corticospinal synaptic plasticity in humans. Ramirez JM, editor. eLife. 2018 Apr 24;7:e34304. Available from: https://doi.org/10.7554/eLife.34304
Navarrete-Opazo A, Mitchell GS. Therapeutic potential of intermittent hypoxia: a matter of dose. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2014 Nov 15 ;307(10):R1181–97. Available from: https://doi. org/10.1152/ajpregu.00208.2014
Klibaite U, Kislin M, Verpeut JL, Bergeler S, Sun X, Shaevitz JW, et al. Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models. Molecular Autism. 2022 Mar 12 ;13(1):12. Available from: https://doi.org/10.1186/s13229-022- 00492-8
Othman MZ, Hassan Z, Has ATC. Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory. Experimental Animals. 2022;71(3):264–80. Available from: https:// doi.org/10.1538/expanim.21-0120
Tsai YW, Yang YR, Sun SH, Liang KC, Wang RY. Post ischemia intermittent hypoxia induces hippocampal neurogenesis and synaptic alterations and alleviates long-term memory impairment. J Cereb Blood Flow Metab. 2013 May;33(5):764–73. Available from: https://doi.org/10.1038/jcbfm.2013.15
Yesudhas A, Roshan SA, Radhakrishnan RK, Abirami GPP, Manickam N, Selvaraj K, et al. Intramuscular Injection of BOTOX® Boosts Learning and Memory in Adult Mice in Association with Enriched Circulation of Platelets and Enhanced Density of Pyramidal Neurons in the Hippocampus. Neurochem Res. 2020 Dec 1;45(12):2856–67. Available from: https://doi.org/10.1007/s11064-020-03133-9
Selvaraj DB, Vergil Andrews JF, Anusuyadevi M, Kandasamy M. Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder. Brain Sci. 2023 Feb 4;13(2):266. Available from: https://doi.org/10.3390/brainsci13020266
Gomez-Pinilla F, Hillman C. The Influence of Exercise on Cognitive Abilities. Compr Physiol. 2013 Jan ;3(1):403–28. Available from: https://doi.org/10.1002/cphy.c110063
Ma S, Mifflin SW, Cunningham JT, Morilak DA. Chronic intermittent hypoxia sensitizes acute hypothalamic–pituitary–adrenal stress reactivity and Fos induction in the rat locus coeruleus in response to subsequent immobilization stress. Neuroscience. 2008 Jul 17 ;154(4):1639–47. Available from: https://doi.org/10.1016/j. neuroscience.2008.04.068
Ventura T, Gomes MC, Carreira T. Cortisol and anxiety response to a relaxing intervention on pregnant women awaiting amniocentesis. Psychoneuroendocrinology. 2012 Jan 1 ;37(1):148–56. Available from: https://doi.org/10.1016/j.psyneuen.2011.05.016
Drigas A, Mitsea E, Skianis C. Intermittent Oxygen Fasting and Digital Technologies: from Antistress and Hormones Regulation to Wellbeing, Bliss and Higher Mental States. Technium BioChemMed. 2022;3(2):55-73. Available from: https://doi.org/10.47577/ biochemmed.v3i2.6628
Belmonte KCD, Harman JC, Lanson NA, Gidday JM. Intra- and intergenerational changes in the cortical DNA methylome in response to therapeutic intermittent hypoxia in mice. Physiological Genomics. 2020 Jan ;52(1):20–34. Available from: https://doi. org/10.1152/physiolgenomics.00094.2019
Liu Y, Tan J, Miao Y, Zhang Q. Neurogenesis, A Potential Target for Intermittent Hypoxia Leading to Cognitive Decline. Current Stem Cell Research & Therapy . ;19(1):63–70. Available from: http:// dx.doi.org/10.2174/1574888X18666230330083206
Published

