Protective effect of Lavandula angustifolia essential oil inhalation on neuromodulators regulating the sleep/wake cycle in rats with total sleep deprivation

Document Type : Original Article

Authors

1 Department of Physiology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

2 Department of Pathology, Burdur Mehmet Akif Ersoy University Faculty of Veterinary Medicine, Burdur, Turkey

3 Department of Chest Diseases, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

4 Fruit Research Institute, Eğirdir/Isparta, Turkey

10.22038/ijbms.2024.78085.16880

Abstract

Objective(s): This study aimed to investigate the potential effects of different doses of Lavender angustifolia essential oil (Lavender EO) administered by inhalation on sleep latency and neuromodulators regulating the sleep/wake cycle in rats with total sleep deprivation (TSD).
Materials and Methods: Forty-eight male Sprague-Dawley rats were divided into five groups: Control, Alprazolam (ALP, 0.25 mg/kg given intraperitoneally), L1 (Lavender EO, 0.3 ml given by inhalation), L2 (Lavender EO, 0.5 ml given by inhalation), and L3 (Lavender EO, 1 ml given by inhalation); TSD was applied to all groups. Rats in SD groups were kept on a platform surrounded by water for 18 hr for 20 days, and for the remaining time, the animals were exposed to Lavender EO for 1 hr (11:00–12:00) and then were kept in their home cage for 5 hr (12:00-17:00). Their brain and brainstem were removed for histopathological and immunohistochemical analyses (c-Fos, ChAT, GAD, and ADRB2 expression) in the locus coeruleus (LC), basal forebrain (BF), and preoptic area (PO).
Results: The groups ranked by the severity of edema, hyperemia, and neurodegeneration in LC, BF, and PO areas were control, L3, L1, L2, and ALP. c-Fos expression significantly decreased in all brain regions in all groups except the L1 group. ChAT and GAD expressions increased dramatically in all brain regions. ADRB2 significantly increased in LC in ALP and L2 groups; in the PO area in ALP, L1, and L2 groups; and in BF in all groups. 
Conclusion: Lavender EO treatment ameliorated c-Fos, ChAT, GAD, and ADRB2 expression, similar to the effect of ALP.

Keywords

Main Subjects


1. Liew SC, Aung T. Sleep deprivation and its association with diseases- a review. Sleep Med 2021; 77:192-204.
2. Wang Z, Yuan K, Ji YB, Li SX, Shi L, Wang Z, et al. Alterations of the gut microbiota in response to total sleep deprivation and recovery sleep in rats. Nat Sci Sleep 2022; 14:121-133.
3. Tobaldini E, Costantino G, Solbiati M, Cogliati C, Kara T, Nobili L, et al. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases. Neurosci Biobehav Rev 2017; 74:321-329.
4. Kiley JP, Twery MJ, Gibbons GH. The national center on sleep disorders research— progress and promise. Sleep 2019; 42:1-5.
5. Salfi F, Lauriola M, Tempesta D, Calanna P, Socci V, De Gennaro L, et al. Effects of total and partial sleep deprivation on reflection ımpulsivity and risk-taking in deliberative decision-making. Nat Sci Sleep 2020; 12:309–324. 
6. Stopford E, Ravi K, Nayar V. The association of sleep disordered breathing with heart failure and other cardiovascular conditions. Cardiol Res Pract 2013; 2013: 356280-356288.
7. Eschenko O, Sara SJ. Learning-dependent, transient ıncrease of activity in noradrenergic neurons of locus coeruleus during slow wave sleep in the rat: Brain stem–cortex ınterplay for memory consolidation? Cereb Cortex 2008; 18: 2596–2603. 
8. Mehta R, Singh S, Khanday MA, Mallick MN. Reciprocal changes in noradrenaline and GABA levels in discrete brain regions upon rapid eye movement sleep deprivation in rats. Neurochem Int 2017;108:190-198.
9. Khadrawy YA, Nour NA, Ezz HSA. Effect of oxidative stress induced by paradoxical sleep deprivation on the activities of Na+, K+-ATPase and acetylcholinesterase in the cortex and hippocampus of rat. Transl Res 2011;157:100-107.
10. Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy, et al. The beneficial effects of regular exercise on cognition in REM sleep deprivation: Behavioral, electrophysiological and molecular evidence. Neurobiol Dis 2012; 45:1153-1162. 
11. Hassani OK, Lee MG, Henny P, Jones BE.  Discharge profiles of ıdentified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep–wake cycle. J Neurosci 2009;29:11828-11840.
12. Rasch B, Buchel C, Gais S, Born J. Odor cues during slowwave sleep prompt declarative memory consolidation. Science 2007; 315:1426-1429.
13. Ghadim MBA, Neisy A, Sisakht M, Khoshdel Z. Lavandula angustifolia aqueous extract ameliorates anxiety and depressive-like behaviors in chronic mild stress-treated male rats. J Med Plants Res 2020;14: 593-603.
14. Manora R, Kumarnsit E, Samerphob N, Rujiralai T, Puangpairote T, Cheaha D. Characterization of pharmaco-EEG fingerprint and sleep-wake profiles of Lavandula angustifolia Mill. essential oil inhalation and diazepam administration in rats. J Ethnopharmacol 2021; 276:114193.
15. Jianu C, Pop G, T Gruia A, Horhat FG. Chemical composition and antimicrobial activity of essential oils of lavender (Lavandula angustifolia) and lavandin (Lavandula×intermedia) grown in Western Romania. Int J Agric Biol 2013; 15: 772-776
16. Hajhashemi V, Ghannadi A, Sharif B. Anti-inflammatory and analgesic properties of the leaf extracts and essential oil of Lavandula angustifolia Mill. J Ethnopharmacol 2003; 89: 67-71.
17. Donatello NN, Emer AA, Salm DC, Ludtke DD, Bordignon SASR, Ferreira JK et al. Lavandula angustifolia essential oil inhalation reduces mechanical hyperalgesia in a model of inflammatory and neuropathic pain: The involvement of opioid and cannabinoid receptors. J Neuroimmunol 2020; 340: 577145.
18. Yogi W, Tsukada M, Sato Y, Izuno T, Inoue T, Tsunokawa Y, et al. Influences of lavender essential oil ınhalation on stress responses during short-duration sleep cycles: A pilot study. Healthcare 2021; 9: 909-918.
19. Vickers A. Why aromatherapy works (even if it doesn’t) and why we need less research. Br J Gen Pract 2000; 50: 444-445.
20. Singh A, Kumar A. Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice. Neurosci Res 2008; 60: 372-379.
21. Xu X, Wang L, Chen L, Su T, Zhang Y, Wang T, et al. Effects of chronic sleep deprivation on bone mass and bone metabolism in rats. J Orthop Surg Res 2016; 11: 1-9.
22. Ma C, Wu G, Wang Z, Wang P, Wu L, Zhu G, et al. Effects of chronic sleep deprivation on the extracellular signal-regulated kinase pathway in the temporomandibular joint of rats. PLoS One 2014; 9: e107544-107551.
23. Sheng M, Greenberg ME. The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 1990; 4:477-485.
24. Cai G, Lu Y, Chen J, Yang D, Yan R, Ren M, et al. Brainwide mapping of c-Fos expression with fluorescence micro-optical sectioning tomography in a chronic sleep deprivation mouse model. Neurobiol Stress 2022; 20: 100478-100490.
25. Javad-oosavi BZ, Nasehi M, Vaseghi S, Jamaldini SH, Zarrindast MR. Activation and inactivation of nicotinic receptnors in the dorsal hippocampal region restored negative effects of total (TSD) and REM sleep deprivation (RSD) on memory acquisition, locomotor activity and pain perception. Neuroscience 2020; 433: 200-211.
26. Benedito MAC, Camarini R. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions. Braz J Med Biol Res 2001; 34: 103-109.
27. Adsersen A, Gauguin B, Gudiksen L, Jäger AK. Screening of plants used in Danish folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity. J Ethnopharmacol 2006; 104: 418-422.
28. Maloney KJ, Mainville L, Jones BE. Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. J Neurosci 1999; 19: 3057-3072.
29. Alnamer R, Alaoui K, Bouidida EH, Benjouad A, Cherrah Y. Sedative and hypnotic activities of the methanolic and aqueous extracts of Lavandula officinalis from Morocco. Advan Pharm Sci 2012; 2012: 270824-270828. 
30. Weinger MB, Ancoli-Israel S. Sleep deprivation and clinical performance. JAMA 2002; 287 957-955.
31.  Norozpour Y, Nasehi M, Sabouri-Khanghah V, Nami M, Vaseghi S,  Zarrindast MR. The effect of alpha-2 adrenergic receptors on memory retention deficit induced by rapid eye movement sleep deprivation. Iran J Basic Med Sci 2020; 23: 1571-1575.
32. Berridge CW, Schmeichel BE, España RA. Noradrenergic modulation of wakefulness/arousal. Sleep Med Rev 2012; 16: 187-197.
33. Berridge CW, Isaac SO, España RA. Additive wake-promoting actions of medial basal forebrain noradrenergic alpha1- and beta-receptor stimulation. Behav Neurosci 2003; 117: 350-359.
34. Berridge CW, Foote SL. Enhancement of behavioral and electroencephalographic indices of waking following stimulation of noradrenergic beta-receptors within the medial septal region of the basal forebrain. J Neurosci 1996; 16: 6999-7009.
35. Pace-Schott EF, Hobson JA. The neurobiology of sleep: Genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 2002; 3:591-605. 
36. Aston-Jones G, Bloom FE. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1981; 1: 876-886.
37. Manns ID, Lee MG, Modirrousta M, Hou YP, Jones BE. Alpha 2 adrenergic receptors on GABAergic, putative sleep‐promoting basal forebrain neurons. Eur J of Neurosci 2003; 18: 723-727.