Sleep and Biological Rhythms

, Volume 16, Issue 3, pp 331–336 | Cite as

Exposure to intermittent hypoxia impairs learning and memory ability in rats

  • Feng Zhang
  • Zhuo Tian
  • Sufen Peng
  • Jie Li
  • Xiang Yang
  • Hailan Mo
  • Jian Tan
  • Hongbing Yao
  • Bing Li
Original Article


To study the effects of chronic intermittent hypoxia (CIH) on learning and memory ability in Sprague–Dawley rats, we established a rat model of CIH. A total of 24 male Sprague–Dawley rats were included and were assigned to three experimental groups (n = 8/group): the unhandled control (UC) group (normal feeding for 4 weeks), the CIH group (CIH for 4 weeks), and the removal of hypoxia (RH) group (normal feeding for 4 weeks after CIH for 4 weeks). All the results were analyzed using one-way ANOVA and comparison between groups was performed using S–N–K method. Performance on the Morris water maze test (a learning and memory test) was significantly worse for CIH rats than for UC rats and RH rats (P < 0.05), but was significantly better for RH rats than for UC rats (P < 0.05). Synaptophysin expression in the CA3 region of the hippocampus was reduced in the CIH group and the RH group compared with the UC group (P < 0.05), but was significantly greater in the RH group than in the CIH group (P < 0.05). Synaptophysin is a calcium-binding protein located in the membranes of presynaptic vesicles. Changes of synaptophysin expression may indirectly reflect the structural changes in the hippocampal CA3 region. In rats, CIH can cause declines in learning ability and memory and reduce the expression of synaptophysin in the CA3 region of the hippocampus; these effects could be partially rescued by the removal of hypoxic factors. The observed decline in learning and memory ability in rats may relate to a decrease in synapse quantity and structural changes in the CA3 region of the hippocampus.


Rats Animal experimentation Morris water maze test Hippocampus Synapses 



We would like to thank all of the authors of the primary studies referenced in this paper. This study was financially supported by the Project of Chongqing Municipal Health Bureau (Grant no. 2012-1-059).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interests.

Ethical committee permission

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.


  1. 1.
    Adams N, Strauss M, Schluchter M, Redline S. Relation of measures of sleep-disordered breathing to neuropsychological functioning. Am J Respir Crit Care Med. 2001;163(7):1626–31. Scholar
  2. 2.
    Mazza S, Pepin JL, Naegele B, Plante J, Deschaux C, Levy P. Most obstructive sleep apnoea patients exhibit vigilance and attention deficits on an extended battery of tests. Eur Respir J. 2005;25(1):75–80. Scholar
  3. 3.
    Engleman HM, Douglas NJ. Sleep. 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome. Thorax. 2004;59(7):618–22.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Aloia MS, Arnedt JT, Davis JD, Riggs RL, Byrd D. Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: a critical review. J Int Neuropsychol Soc. 2004;10(5):772–85. Scholar
  5. 5.
    Twigg GL, Papaioannou I, Jackson M, Ghiassi R, Shaikh Z, Jaye J, Graham KS, Simonds AK, Morrell MJ. Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory. Am J Respir Crit Care Med. 2010;182(1):98–103. Scholar
  6. 6.
    Blunden S, Lushington K, Kennedy D, Martin J, Dawson D. Behavior and neurocognitive performance in children aged 5–10 years who snore compared to controls. J Clin Exp Neuropsychol. 2000;22(5):554–68.;1-9;FT554.CrossRefPubMedGoogle Scholar
  7. 7.
    Alchanatis M, Zias N, Deligiorgis N, Amfilochiou A, Dionellis G, Orphanidou D. Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory. J Sleep Res. 2005;14(1):69–75. Scholar
  8. 8.
    Saunamaki T, Jehkonen M. A review of executive functions in obstructive sleep apnea syndrome. Acta Neurol Scand. 2007;115(1):1–11. Scholar
  9. 9.
    Jennum P, Hein HO, Suadicani P, Gyntelberg F. Cognitive function and snoring. Sleep. 1993;16(8 Suppl):S62-64.Google Scholar
  10. 10.
    Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol. 2005;25(1):117–29. Scholar
  11. 11.
    Ferini-Strambi L, Baietto C, Di Gioia MR, Castaldi P, Castronovo C, Zucconi M, Cappa SF. Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP). Brain Res Bull. 2003;61(1):87–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Rao BS, Raju TR, Meti BL. Increased numerical density of synapses in CA3 region of hippocampus and molecular layer of motor cortex after self-stimulation rewarding experience. Neuroscience. 1999;91(3):799–803.CrossRefPubMedGoogle Scholar
  13. 13.
    Sarnat HB, Born DE. Synaptophysin immunocytochemistry with thermal intensification: a marker of terminal axonal maturation in the human fetal nervous system. Brain Dev. 1999;21(1):41–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Wang L, Peng R, Hu X. [Relationship of synaptophysin and regulation of characteristics of synaptic plasticity with nervous system diseases]. Chin J Clin Rehabil. 2005;9(1):155–7.CrossRefGoogle Scholar
  15. 15.
    Fletcher EC. Invited review: Physiological consequences of intermittent hypoxia: systemic blood pressure. J Appl Physiol (1985). 2001;90(4):1600–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Raz N, Gunning-Dixon FM, Head D, Dupuis JH, Acker JD. Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging. Neuropsychology. 1998;12(1):95–114.CrossRefPubMedGoogle Scholar
  17. 17.
    Macey PM, Henderson LA, Macey KE, Alger JR, Frysinger RC, Woo MA, Harper RK, Yan-Go FL, Harper RM. Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med. 2002;166(10):1382–7. Scholar
  18. 18.
    Dalm S, Grootendorst J, de Kloet ER, Oitzl MS. Quantification of swim patterns in the Morris water maze. Behav Res Methods Instrum Comput. 2000;32(1):134–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Morrell MJ, McRobbie DW, Quest RA, Cummin AR, Ghiassi R, Corfield DR. Changes in brain morphology associated with obstructive sleep apnea. Sleep Med. 2003;4(5):451–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Farre R, Nacher M, Serrano-Mollar A, Galdiz JB, Alvarez FJ, Navajas D, Montserrat JM. Rat model of chronic recurrent airway obstructions to study the sleep apnea syndrome. Sleep. 2007;30(7):930–3.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mueller SG, Schuff N, Raptentsetsang S, Elman J, Weiner MW. Selective effect of Apo e4 on CA3 and dentate in normal aging and Alzheimer’s disease using high resolution MRI at 4 T. Neuroimage. 2008;42(1):42–8. Scholar
  22. 22.
    Zhang FX, Sun QJ, Zheng XY, Lin YT, Shang W, Wang AH, et al. Abnormal expression of synaptophysin, SNAP-25, and synaptotagmin 1 in the hippocampus of kainic acid-exposed rats with behavioral deficits. Cell Mol Neurobiol. 2014;34(6):813–24.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Sleep Research 2018

Authors and Affiliations

  • Feng Zhang
    • 1
  • Zhuo Tian
    • 2
  • Sufen Peng
    • 3
  • Jie Li
    • 3
  • Xiang Yang
    • 3
  • Hailan Mo
    • 3
  • Jian Tan
    • 3
  • Hongbing Yao
    • 1
  • Bing Li
    • 3
  1. 1.Department of OtolaryngologyThe Children’s Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Department of GeratologyChongqing General HospitalChongqingChina
  3. 3.Department of OtolaryngologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

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