Saint Petersburg, St. Petersburg, Russian Federation
from 01.01.2019 to 01.01.2024
Pavlov Institute of Physiology RAS
from 01.01.1999 to 01.01.2022
Saint Petersburg, St. Petersburg, Russian Federation
The article is focused on the effect of short-term hypoxia on the olfactory sensitivity. The effect of short-term hypoxia on the olfactory sensitivity in human and rats were studied by determination thresholds for n-butanol. We have shown that reduced oxygen partial pressure leads to reduction of olfactory sensitivity. As known, odorant detection thresholds characterize the functional state of receptor cells. It can be assumed that the weakening of their sensitivity may be caused by a lack of energy supply to the olfactory perception process in hypoxia. To test this hypothesis, we stimulated rat olfactory sensory neurons with n-butanol in rotenone model. The reaction of cellular respiration of olfactory sensory neurons was evaluated by changing the intensity of intrinsic fluorescence of reduced pyridine nucleotides (NADH) according to the B. Chance method. Analysis of the results showed that under normoxia, stimulation of olfactory neurons by odorant caused an increase in the intensity of NADH fluorescence, which indicates the accumulation of the reduced form of pyridine nucleotides in mitochondria, and, consequently, the activation of cellular respiration due to exposure to odorant. In hypoxia caused by rotenone, an increase in the induced change of fluorescence of NADH was either not registered or the amplitude of the reaction was halved. This means that the recovery of NADH due to the odorant either did not occur at all, or this reaction to the smell was significantly lower than with normoxia, which indicates a weakening of cellular respiration during hypoxia. This is the reason for the decrease in ATP synthesis, which affects the efficiency of the olfactory transduction process and the sensitivity of olfactory sensory neurons. Therefore, based on our results, it can be concluded that the weakening of olfactory sensitivity in rats and humans with hypoxia may be due to a weakening of cellular respiration in olfactory sensory neurons.
olfactory sensitivity, olfactory epithelium, short-term hypoxia, odorants, olfactory sensory neuron
1. Son G. et al. Olfactory neuropathology in Alzheimer’s disease: A sign of ongoing neurodegeneration. BMB reports, 2021, vol. 54, no. 6, p. 295, doi:https://doi.org/10.5483/BMBRep.2021.54.6.055.
2. Hawkes C. Olfaction in neurodegenerative disorder. Taste and Smell, 2006, vol. 63, pp. 133-151.
3. Hawkes C.H., Shephard B.C. Selective anosmia in Parkinson's disease? The Lancet, 1993, vol. 341, no. 8842, pp. 435-436.
4. Peers C., Pearson H.A., Boyle J.P. Hypoxia and Alzheimer’s disease. Essays in biochemistry, 2007, vol. 43, pp. 153-164.
5. Chen G.J. et al. Transient hypoxia causes Alzheimer-type molecular and biochemical abnormalities in cortical neurons: potential strategies for neuroprotection. Journal of Alzheimer's Disease, 2003, vol. 5, no. 3, pp. 209-228.
6. Zhang X., Le W. Pathological role of hypoxia in Alzheimer's disease. Experimental neurology, 2010, vol. 223, no. 2, pp. 299-303.
7. Saramago I., Franceschi A.M. Olfactory dysfunction in neurodegenerative disease. Topics in Magnetic Resonance Imaging, 2021, vol. 30, no. 3, pp. 167-172, doi:https://doi.org/10.1097/RMR.0000000000000271.
8. Turetsky B.I., Moberg P.J. An odor-specific threshold deficit implicates abnormal intracellular cyclic AMP signaling in schizophrenia. American Journal of Psychiatry, 2009, vol. 166, no. 2, pp. 226-233.
9. Ruffini R. et al. Adaptation of olfactory threshold at high altitude. Neurotransmitter Interactions and Cognitive Function, Springer, Cham, 2014, pp. 19-22.
10. Hummel T. et al. “Sniffin’sticks”: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chemical senses, 1997, vol. 22, no. 1, pp. 39-52.
11. Cain W.S., Rabin M.D. Comparability of two tests of olfactory functioning. Chemical Senses, 1989, vol. 14, no. 4, pp. 479-485.
12. Bigdai E.V. et al. The change in oxygen tension in the olfactory epithelium of the rat when exposed to odorants. Biophysics, 2019, no. 4, pp. 772-777 (In Russ.).
13. Chance B., Connelly C.M. A method for the estimation of the increase in concentration of adenosine diphosphate in muscle sarcosomes following a contraction. Nature, 1957, vol. 179, no. 4572, pp. 1235-1237.
14. Karnaukhov V.N. Luminescent spectral analysis of a cell. Science, 1978 (In Russ.).
15. Doane M.J. J. Gen. Physiol., 1967, vol. 50, 2603 p.
16. Divakaruni A.S. et al. Analysis and interpretation of microplate-based oxygen consumption and pH data. Methods in enzymology, Academic Press, 2014, vol. 547, pp. 309-354.
17. Archer S., Michelakis E. The mechanism (s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O2 sensors, and controversies. Physiology, 2002, vol. 17, no. 4, pp. 131-137.
18. Bigdai E.V. et al. The effect of odorants on mitochondrial respiration of olfactory cells. Bulletin of the Russian Military Medical Academy, 2004, vol. 11, no. 1, p. 29 (In Russ.).
19. Yu C.R. et al. Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron, 2004, vol. 42, no. 4, pp. 553-566.
