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Erschienen in: Sleep and Breathing 1/2021

19.06.2020 | Sleep Breathing Physiology and Disorders • Original Article

The dorsal and the ventral side of hypoglossal motor nucleus showed different response to chronic intermittent hypoxia in rats

verfasst von: Rui Cao, Min-Juan Zhang, Yun-Tao Zhou, Ya-Jie Liu, Huan-Huan Wang, Qin-Xin Zhang, Ya-Wen Shi, Jia-Chen Li, Thian-Sze Wong, Min Yin

Erschienen in: Sleep and Breathing | Ausgabe 1/2021

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Abstract

Purpose

To study neurochemical reactions to chronic intermittent hypoxia (CIH) in the hypoglossal nucleus (HN) of rats.

Methods

Adult male Sprague-Dawley rats (n = 12) were randomly divided into two groups (the CIH and the control group). The CIH rats were housed in a hypoxic chamber with the fraction of oxygen volume alternating between 21% and 5% by providing air for 60 s and then providing nitrogen for 60 s from 8:30 am to 16:30 pm each day for 35 days. The control group was housed in a cabin with normal oxygen levels. We studied the expression of c-fos protein, 5-hydroxytryptamine (5-HT) positive terminals, and its 2A receptors in hypoglossal nuclei by immunohistochemistry.

Results

The expression of c-fos, 5-HT positive terminals, and accordingly 5-HT 2A receptors in the CIH group were significantly higher than that in the controls (p < 0.05). The ventral side of the HN showed a clearly higher expression of 5-HT and its 2A receptors than the dorsal side (p < 0.05).

Conclusion

There were 2 responses of the HN to CIH. First, CIH induced a higher expression of 5-HT positive terminals and its 2A receptors, and second, this reaction was much more evident in ventral side than in the dorsal side. We postulate that these responses may serve to be a protective and compensatory mechanism for CIH.
Literatur
1.
Zurück zum Zitat White DP (2006) The pathogenesis of obstructive sleep apnea: advances in the past 100 years. Am J Respir Cell Mol Biol 34:1–6 PubMed White DP (2006) The pathogenesis of obstructive sleep apnea: advances in the past 100 years. Am J Respir Cell Mol Biol 34:1–6 PubMed
2.
Zurück zum Zitat Bucks RS, Olaithe M, Rosenzweig I, Morrell MJ (2017) Reviewing the relationship between OSA and cognition: where do we go from here? Respirology 22:1253–1261 PubMed Bucks RS, Olaithe M, Rosenzweig I, Morrell MJ (2017) Reviewing the relationship between OSA and cognition: where do we go from here? Respirology 22:1253–1261 PubMed
3.
Zurück zum Zitat Suratt PM, Mctier RF, Wilhoit SC (1988) Upper airway muscle activation is augmented in patients with obstructive sleep apnea compared with that in normal subjects. Am Rev Respir Dis 137:889–894 PubMed Suratt PM, Mctier RF, Wilhoit SC (1988) Upper airway muscle activation is augmented in patients with obstructive sleep apnea compared with that in normal subjects. Am Rev Respir Dis 137:889–894 PubMed
4.
Zurück zum Zitat Rodenstein DO, Dooms G, Thomas Y, Liistro G, Stanescu DC, Culée C, Aubert-Tulkens G (1990) Pharyngeal shape and dimension in healthy subjects, snorers, and patients with obstructive sleep apnea. Thorax 45:722–727 PubMedPubMedCentral Rodenstein DO, Dooms G, Thomas Y, Liistro G, Stanescu DC, Culée C, Aubert-Tulkens G (1990) Pharyngeal shape and dimension in healthy subjects, snorers, and patients with obstructive sleep apnea. Thorax 45:722–727 PubMedPubMedCentral
5.
Zurück zum Zitat Whyte A, Gibson D (2018) Imaging of adult obstructive sleep apnoea. Eur J Radiol 102:176–187 PubMed Whyte A, Gibson D (2018) Imaging of adult obstructive sleep apnoea. Eur J Radiol 102:176–187 PubMed
6.
Zurück zum Zitat Mezzanotte WS, Tangel DJ, White DP (1992) Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 89:1571–1579 PubMedPubMedCentral Mezzanotte WS, Tangel DJ, White DP (1992) Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 89:1571–1579 PubMedPubMedCentral
7.
Zurück zum Zitat Hendricks JC, Petrof BJ, Panckeri K, Pack AI (1993) Upper airway dilating muscle hyperactivity during non-rapid eye movement sleep in English bulldogs. Am Rev Respir Dis 148:185–194 PubMed Hendricks JC, Petrof BJ, Panckeri K, Pack AI (1993) Upper airway dilating muscle hyperactivity during non-rapid eye movement sleep in English bulldogs. Am Rev Respir Dis 148:185–194 PubMed
8.
Zurück zum Zitat Saboisky JP, Butler JE, Mckenzie DK, Gorman RB, Trinder JA, White DP, Gandevia SC (2007) Neural drive to human genioglossus in obstructive sleep apnoea. J Physiol 585:135–146 PubMedPubMedCentral Saboisky JP, Butler JE, Mckenzie DK, Gorman RB, Trinder JA, White DP, Gandevia SC (2007) Neural drive to human genioglossus in obstructive sleep apnoea. J Physiol 585:135–146 PubMedPubMedCentral
9.
Zurück zum Zitat Oliven R, Cohen G, Dotan Y, Somri M, Schwartz AR, Oliven A (2018) Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects. J Appl Physiol 124:421–429 PubMed Oliven R, Cohen G, Dotan Y, Somri M, Schwartz AR, Oliven A (2018) Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects. J Appl Physiol 124:421–429 PubMed
10.
Zurück zum Zitat Mezzanotte WS, Tangel DJ, White DP (1996) Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am J Respir Crit Care Med 153:1880–1887 PubMed Mezzanotte WS, Tangel DJ, White DP (1996) Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am J Respir Crit Care Med 153:1880–1887 PubMed
11.
Zurück zum Zitat Oliven R, Cohen G, Somri M, Schwartz AR, Oliven A (2019) Spectral analysis of peri-pharyngeal muscles’ EMG in patients with OSA and healthy subjects. Respir Physiol Neurobiol 260:53–57 PubMed Oliven R, Cohen G, Somri M, Schwartz AR, Oliven A (2019) Spectral analysis of peri-pharyngeal muscles’ EMG in patients with OSA and healthy subjects. Respir Physiol Neurobiol 260:53–57 PubMed
12.
Zurück zum Zitat Lowe AA (1980) The neural regulation of tongue movements. Prog Neurobiol 15:295–344 PubMed Lowe AA (1980) The neural regulation of tongue movements. Prog Neurobiol 15:295–344 PubMed
13.
Zurück zum Zitat Berger AJ (2011) Development of synaptic transmission to respiratory motoneurons. Respir Physiol Neurobiol 179:34–42 PubMedPubMedCentral Berger AJ (2011) Development of synaptic transmission to respiratory motoneurons. Respir Physiol Neurobiol 179:34–42 PubMedPubMedCentral
14.
Zurück zum Zitat Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith P (1996) Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 81:643–652 PubMed Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith P (1996) Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 81:643–652 PubMed
15.
Zurück zum Zitat Cascella M (2016) The intercalatus nucleus of Staderini. J Hist Neurosci 25:408–419 PubMed Cascella M (2016) The intercalatus nucleus of Staderini. J Hist Neurosci 25:408–419 PubMed
16.
Zurück zum Zitat McClung JR, Goldberg SJ (2002) Organization of the hypoglossal motoneurons that innervate the horizontal and oblique components of the genioglossus muscle in the rat. Brain Res 950:321–324 PubMed McClung JR, Goldberg SJ (2002) Organization of the hypoglossal motoneurons that innervate the horizontal and oblique components of the genioglossus muscle in the rat. Brain Res 950:321–324 PubMed
17.
Zurück zum Zitat Wu X, Lu H, Hu L, Gong W, Wang J, Fu C, Liu Z, Li S (2017) Chronic intermittent hypoxia affects endogenous serotonergic inputs and expression of synaptic proteins in rat hypoglossal nucleus. Am J Transl Res 9:546–557 PubMedPubMedCentral Wu X, Lu H, Hu L, Gong W, Wang J, Fu C, Liu Z, Li S (2017) Chronic intermittent hypoxia affects endogenous serotonergic inputs and expression of synaptic proteins in rat hypoglossal nucleus. Am J Transl Res 9:546–557 PubMedPubMedCentral
18.
Zurück zum Zitat Nie X, Zhou L, Wang A, Jin H, Qin Z, Pang J, Wang W, Kang J (2017) Noradrenergic activation of hypoglossal nucleus modulates the central regulation of genioglossus in chronic intermittent hypoxic rats. Front Neurol 8:171 PubMedPubMedCentral Nie X, Zhou L, Wang A, Jin H, Qin Z, Pang J, Wang W, Kang J (2017) Noradrenergic activation of hypoglossal nucleus modulates the central regulation of genioglossus in chronic intermittent hypoxic rats. Front Neurol 8:171 PubMedPubMedCentral
19.
Zurück zum Zitat Liu ZL, Wu X, Luo YJ, Wang L, Qu WM, Li SQ, Huang ZL (2016) Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons. J Neurochem 137:277–286 PubMed Liu ZL, Wu X, Luo YJ, Wang L, Qu WM, Li SQ, Huang ZL (2016) Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons. J Neurochem 137:277–286 PubMed
20.
Zurück zum Zitat Waldvogel HJ, Biggins FM, Singh A, Arasaratnam CJ, Faull RLM (2019) Variable colocalisation of GABAA receptor subunits and glycine receptors on neurons in the human hypoglossal nucleus. J Chem Neuroanat 97:99–111 PubMed Waldvogel HJ, Biggins FM, Singh A, Arasaratnam CJ, Faull RLM (2019) Variable colocalisation of GABAA receptor subunits and glycine receptors on neurons in the human hypoglossal nucleus. J Chem Neuroanat 97:99–111 PubMed
21.
Zurück zum Zitat Volgin DV, Fay R, Kubin L (2003) Postnatal development of serotonin 1B, 2 A and 2C receptors in brainstem motoneurons. Eur J Neurosci 17:1179–1188 PubMed Volgin DV, Fay R, Kubin L (2003) Postnatal development of serotonin 1B, 2 A and 2C receptors in brainstem motoneurons. Eur J Neurosci 17:1179–1188 PubMed
22.
Zurück zum Zitat Rukhadze I, Fenik VB, Benincasa KE, Price A, Kubin L (2010) Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus. Am J Respir Crit Care Med 182:1321–1329 PubMedPubMedCentral Rukhadze I, Fenik VB, Benincasa KE, Price A, Kubin L (2010) Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus. Am J Respir Crit Care Med 182:1321–1329 PubMedPubMedCentral
23.
Zurück zum Zitat Bayliss DA, Viana F, Talley EM, Berger AJ (1997) Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms. Respir Physiol 110:139–150 PubMed Bayliss DA, Viana F, Talley EM, Berger AJ (1997) Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms. Respir Physiol 110:139–150 PubMed
24.
Zurück zum Zitat Iwasaki K, Komiya H, Kakizaki M, Miyoshi C, Abe M, Sakimura K, Funato H, Yanagisawa M (2018) Ablation of central serotonergic neurons decreased REM sleep and attenuated arousal response. Front Neurosci 12:535 PubMedPubMedCentral Iwasaki K, Komiya H, Kakizaki M, Miyoshi C, Abe M, Sakimura K, Funato H, Yanagisawa M (2018) Ablation of central serotonergic neurons decreased REM sleep and attenuated arousal response. Front Neurosci 12:535 PubMedPubMedCentral
25.
Zurück zum Zitat Trulson ME, Trulson VM (1982) Activity of nucleus raphe pallidus neurons across the sleep-waking cycle in freely moving cats. Brain Res 237:232–237 PubMed Trulson ME, Trulson VM (1982) Activity of nucleus raphe pallidus neurons across the sleep-waking cycle in freely moving cats. Brain Res 237:232–237 PubMed
26.
Zurück zum Zitat Joo JY, Schaukowitch K, Farbiak L, Kilaru G, Kim TK (2016) Stimulus-specific combinatorial functionality of neuronal c-fos enhancers. Nat Neurosci 19:75–83 PubMed Joo JY, Schaukowitch K, Farbiak L, Kilaru G, Kim TK (2016) Stimulus-specific combinatorial functionality of neuronal c-fos enhancers. Nat Neurosci 19:75–83 PubMed
27.
Zurück zum Zitat Yin X, Zhang X, Lv C, Li C, Yu Y, Wang X, Han F (2015) Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia. Sci Rep 5:14507 PubMedPubMedCentral Yin X, Zhang X, Lv C, Li C, Yu Y, Wang X, Han F (2015) Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia. Sci Rep 5:14507 PubMedPubMedCentral
28.
Zurück zum Zitat Itoh H, Yagi M, Fushida S, Tani T, Hashimoto T, Shimizu K, Miwa K (2000) Activation of immediate early gene, c-fos, and c-jun in the rat small intestine after ischemia/reperfusion. Transplantation 69:598–604 PubMed Itoh H, Yagi M, Fushida S, Tani T, Hashimoto T, Shimizu K, Miwa K (2000) Activation of immediate early gene, c-fos, and c-jun in the rat small intestine after ischemia/reperfusion. Transplantation 69:598–604 PubMed
29.
Zurück zum Zitat Heurteaux C, Bertaina V, Widmann C, Lazdunski M (1993) K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid β-protein precursor genes and neuronal death in rat hippocampus. Proc Natl Acad Sci U S A 90:9431–9435 PubMedPubMedCentral Heurteaux C, Bertaina V, Widmann C, Lazdunski M (1993) K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid β-protein precursor genes and neuronal death in rat hippocampus. Proc Natl Acad Sci U S A 90:9431–9435 PubMedPubMedCentral
30.
Zurück zum Zitat Paxinos G, Watson C (1985) Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J Neurosci Methods 13:139–143 PubMed Paxinos G, Watson C (1985) Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J Neurosci Methods 13:139–143 PubMed
31.
Zurück zum Zitat Pae EK, Hyatt JP, Wu J, Chien P (2007) Short-term electrical stimulation alters tongue muscle fibre type composition. Arch Oral Biol 52:544–551 PubMed Pae EK, Hyatt JP, Wu J, Chien P (2007) Short-term electrical stimulation alters tongue muscle fibre type composition. Arch Oral Biol 52:544–551 PubMed
32.
Zurück zum Zitat Series FJ, Simoneau SA, St Pierre S, Marc I (1996) Characteristics of the genioglossus and musculus uvulae in sleep apnea hypopnea syndrome and in snorers. Am J Respir Crit Care Med 153:1870–1874 PubMed Series FJ, Simoneau SA, St Pierre S, Marc I (1996) Characteristics of the genioglossus and musculus uvulae in sleep apnea hypopnea syndrome and in snorers. Am J Respir Crit Care Med 153:1870–1874 PubMed
33.
Zurück zum Zitat Wealing JC, Cholanian M, Flanigan EG, Levine RB, Fregosi RF (2019) Diverse physiological properties of hypoglossal motoneurons innervating intrinsic and extrinsic tongue muscles. J Neurophysiol 122:2054–2060 PubMedPubMedCentral Wealing JC, Cholanian M, Flanigan EG, Levine RB, Fregosi RF (2019) Diverse physiological properties of hypoglossal motoneurons innervating intrinsic and extrinsic tongue muscles. J Neurophysiol 122:2054–2060 PubMedPubMedCentral
34.
Zurück zum Zitat Mukai T, Nagao Y, Nishioka S (2013) Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice. Neurosci Res 77:202–207 PubMed Mukai T, Nagao Y, Nishioka S (2013) Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice. Neurosci Res 77:202–207 PubMed
35.
Zurück zum Zitat Greenberg HE, Sica AL, Scharf SM, Ruggiero DA (1999) Expression of c-fos in the rat brainstem after chronic intermittent hypoxia. Brain Res 816:638–645 PubMed Greenberg HE, Sica AL, Scharf SM, Ruggiero DA (1999) Expression of c-fos in the rat brainstem after chronic intermittent hypoxia. Brain Res 816:638–645 PubMed
36.
Zurück zum Zitat Sica AL, Greenberg HE, Scharf SM, Ruggiero DA (2000) Chronic-intermittent hypoxia induces immediate early gene expression in the midline thalamus and epithalamus. Brain Res 883:224–228 PubMed Sica AL, Greenberg HE, Scharf SM, Ruggiero DA (2000) Chronic-intermittent hypoxia induces immediate early gene expression in the midline thalamus and epithalamus. Brain Res 883:224–228 PubMed
37.
Zurück zum Zitat Das RK, Herr KB, Parkar A, Kubin L (2019) Increased tongue use enhances 5-HT 2C receptor immunostaining in hypoglossal motor nucleus. Respir Physiol Neurobiol 260:105–113 PubMed Das RK, Herr KB, Parkar A, Kubin L (2019) Increased tongue use enhances 5-HT 2C receptor immunostaining in hypoglossal motor nucleus. Respir Physiol Neurobiol 260:105–113 PubMed
38.
Zurück zum Zitat Taranto-Montemurro L, Sands SA, Grace KP, Azarbarzin A, Messineo L, Salant R, White DP, Wellman DA (2018) Neural memory of the genioglossus muscle during sleep is stage-dependent in healthy subjects and obstructive sleep apnoea patients. J Physiol 596:5163–5173 PubMedPubMedCentral Taranto-Montemurro L, Sands SA, Grace KP, Azarbarzin A, Messineo L, Salant R, White DP, Wellman DA (2018) Neural memory of the genioglossus muscle during sleep is stage-dependent in healthy subjects and obstructive sleep apnoea patients. J Physiol 596:5163–5173 PubMedPubMedCentral
39.
Zurück zum Zitat Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI (1993) Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing. Am Rev Respir Dis 148:1385–1400 PubMed Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI (1993) Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing. Am Rev Respir Dis 148:1385–1400 PubMed
40.
Zurück zum Zitat Schulz R, Murzabekova G, Egemnazarov B, Kraut S, Eisele HJ, Dumitrascu R, Heitmann J, Seimetz M, Witzenrath M, Ghofrani HA, Schermuly RT, Grimminger F, Seeger W, Weissmann N (2014) Arterial hypertension in a murine model of sleep apnea: role of NADPH oxidase 2. J Hypertens 32:300–305 PubMed Schulz R, Murzabekova G, Egemnazarov B, Kraut S, Eisele HJ, Dumitrascu R, Heitmann J, Seimetz M, Witzenrath M, Ghofrani HA, Schermuly RT, Grimminger F, Seeger W, Weissmann N (2014) Arterial hypertension in a murine model of sleep apnea: role of NADPH oxidase 2. J Hypertens 32:300–305 PubMed
41.
Zurück zum Zitat Soukhova-O'Hare GK, Shah ZA, Lei Z, Nozdrachev AD, Rao CV, Gozal D (2008) Erectile dysfunction in a murine model of sleep apnea. Am J Respir Crit Care Med 178:644–650 PubMedPubMedCentral Soukhova-O'Hare GK, Shah ZA, Lei Z, Nozdrachev AD, Rao CV, Gozal D (2008) Erectile dysfunction in a murine model of sleep apnea. Am J Respir Crit Care Med 178:644–650 PubMedPubMedCentral
42.
Zurück zum Zitat Wang Y, Hai B, Niu X, Ai L, Cao Y, Li R, Li Y (2017) Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway. Biochem Cell Biol 95:415–420 PubMed Wang Y, Hai B, Niu X, Ai L, Cao Y, Li R, Li Y (2017) Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway. Biochem Cell Biol 95:415–420 PubMed
43.
Zurück zum Zitat Liu F, Liu TW, Kang J (2018) The role of NF-kappaB-mediated JNK pathway in cognitive impairmentof sleep apnea. J Thorac Dis 10:6921–6931 PubMedPubMedCentral Liu F, Liu TW, Kang J (2018) The role of NF-kappaB-mediated JNK pathway in cognitive impairmentof sleep apnea. J Thorac Dis 10:6921–6931 PubMedPubMedCentral
Metadaten
Titel
The dorsal and the ventral side of hypoglossal motor nucleus showed different response to chronic intermittent hypoxia in rats
verfasst von
Rui Cao
Min-Juan Zhang
Yun-Tao Zhou
Ya-Jie Liu
Huan-Huan Wang
Qin-Xin Zhang
Ya-Wen Shi
Jia-Chen Li
Thian-Sze Wong
Min Yin
Publikationsdatum
19.06.2020
Verlag
Springer International Publishing
Erschienen in
Sleep and Breathing / Ausgabe 1/2021
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-020-02125-x

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