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Published in: Respiratory Research 1/2014

Open Access 01-12-2014 | Research

Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats

Authors: Jiao Su, Wei Wang, Longfeng Sun, Ting Li, Delei Kong, Jian Kang

Published in: Respiratory Research | Issue 1/2014

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Abstract

Background

Genioglossus activity is greater during wakefulness but decreases to a weaker state during sleep in obstructive sleep apnea syndrome (OSAS) patients, compared to healthy subjects. Previous studies suggested that the corticomotor control of the genioglossus was modified in OSAS patients. Intermittent hypoxia (IH), the typical pathophysiological change in OSAS, can induce genioglossus facilitation. The serotonergic neurons of the raphe dorsal (DRN) and magnus nuclei (RMg) are responsive to hypoxia and play important roles in the control of the genioglossus. However, it remains unknown whether DRN and RMg serotonergic neurons are responsible for the facilitated corticomotor activity of the genioglossus during IH. This study explored the influence of IH on the corticomotor activity of the genioglossus by transcranial magnetic stimulation (TMS), and the role of DRN and RMg serotonergic neurons in this effect.

Methods

Rats were exposed to IH and divided into two groups. In one group, anti-SERT-SAP was microinjected into the DRN and RMg respectively to kill serotonergic neurons. In the other group, artificial cerebrospinal fluid (ACSF) was injected. Comparisons were conducted between the two groups during four weeks of IH and four weeks after IH.

Results

Compared to the corresponding ACSF-injected group, the DRN lesion group and RMg lesion group showed longer TMS latencies and lower amplitudes during IH from the 1st to the 28th day. After 28 days of IH, longer latencies and lower amplitudes were seen only in the DRN lesion group.

Conclusion

These results indicate that DRN and RMg serotonergic neurons play different roles in the facilitation of genioglossus corticomotor activity induced by IH.
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Literature
1.
go back to reference Mezzanotte WS, Tangel DJ, White DP: Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest. 1992, 89: 1571-1579.PubMedPubMedCentralCrossRef Mezzanotte WS, Tangel DJ, White DP: Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest. 1992, 89: 1571-1579.PubMedPubMedCentralCrossRef
2.
go back to reference Sériès F, Wang W, Similowski T: Corticomotor control of the genioglossus in awake OSAS patients: a transcranial magnetic stimulation study. Respir Res. 2009, 10: 74-83.PubMedPubMedCentralCrossRef Sériès F, Wang W, Similowski T: Corticomotor control of the genioglossus in awake OSAS patients: a transcranial magnetic stimulation study. Respir Res. 2009, 10: 74-83.PubMedPubMedCentralCrossRef
3.
go back to reference Wang W, Kang J, Kong DL: The central motor conductivity of genioglossus in obstructive sleep apnoea. Respirology. 2010, 15: 1209-1214.PubMedCrossRef Wang W, Kang J, Kong DL: The central motor conductivity of genioglossus in obstructive sleep apnoea. Respirology. 2010, 15: 1209-1214.PubMedCrossRef
4.
go back to reference Ryan S, Nolan P: Episodic hypoxia induces long-term facilitation of upper airway muscle activity in spontaneously breathing anaesthetized rats. J Physiol. 2009, 587: 3329-3342.PubMedPubMedCentralCrossRef Ryan S, Nolan P: Episodic hypoxia induces long-term facilitation of upper airway muscle activity in spontaneously breathing anaesthetized rats. J Physiol. 2009, 587: 3329-3342.PubMedPubMedCentralCrossRef
5.
go back to reference Li T, Wang W, Kong DL, Su J, Kang J: Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2012, 35: 283-285.PubMed Li T, Wang W, Kong DL, Su J, Kang J: Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats. Zhonghua Jie He He Hu Xi Za Zhi. 2012, 35: 283-285.PubMed
6.
go back to reference Reid G, Rand M: Physiological actions of the partially purified neurons serum vasoconstrictor (serotonin). Aust J Exp Biol Med Sci. 1951, 29: 401-415.PubMedCrossRef Reid G, Rand M: Physiological actions of the partially purified neurons serum vasoconstrictor (serotonin). Aust J Exp Biol Med Sci. 1951, 29: 401-415.PubMedCrossRef
7.
go back to reference Hilaire G, Morin D, Lajard AM, Monteau R: Changes in serotonin metabolism may elicit obstructive apnoea in the newborn rat. J Physiol. 1993, 466: 367-381.PubMedPubMedCentral Hilaire G, Morin D, Lajard AM, Monteau R: Changes in serotonin metabolism may elicit obstructive apnoea in the newborn rat. J Physiol. 1993, 466: 367-381.PubMedPubMedCentral
8.
go back to reference Zhong YJ, Zhang C, Wang GF: Effect of 5-hydrotryptamine and 5-hydrotryptamine 2A2C agonist on the genioglossus activity and sleep apnea in rats. Chin Med J (Engl). 2010, 123 (15): 2094-2098. Zhong YJ, Zhang C, Wang GF: Effect of 5-hydrotryptamine and 5-hydrotryptamine 2A2C agonist on the genioglossus activity and sleep apnea in rats. Chin Med J (Engl). 2010, 123 (15): 2094-2098.
9.
go back to reference Sood S, Liu X, Liu H, Nolan P, Horner RL: 5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats. Respir Physiol Neurobiol. 2003, 138 (2–3): 205-221.PubMedCrossRef Sood S, Liu X, Liu H, Nolan P, Horner RL: 5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats. Respir Physiol Neurobiol. 2003, 138 (2–3): 205-221.PubMedCrossRef
10.
go back to reference Fay RA, Norqren R: Identification of rat brain multisynaptic connections to the oral motor nuclei using pseudorabies virus: III: lingual muscle motor systems. Brain Res Brain Res Rev. 1997, 25: 291-311.PubMedCrossRef Fay RA, Norqren R: Identification of rat brain multisynaptic connections to the oral motor nuclei using pseudorabies virus: III: lingual muscle motor systems. Brain Res Brain Res Rev. 1997, 25: 291-311.PubMedCrossRef
11.
go back to reference Barker JR, Thomas CF, Behan M: 5-HT projections from the caudal raphe nuclei to the hypoglossal nucleus in male and female rats. Respir Physiol Neurobiol. 2009, 165: 175-184.PubMedPubMedCentralCrossRef Barker JR, Thomas CF, Behan M: 5-HT projections from the caudal raphe nuclei to the hypoglossal nucleus in male and female rats. Respir Physiol Neurobiol. 2009, 165: 175-184.PubMedPubMedCentralCrossRef
12.
go back to reference McKay LC, Janczewski WA, Feldman JL: Episodic hypoxia evokes long-term facilitation of genioglossus muscle activity in neonatal rats. J Physiol. 2004, 557 (Pt 1): 13-18.PubMedPubMedCentralCrossRef McKay LC, Janczewski WA, Feldman JL: Episodic hypoxia evokes long-term facilitation of genioglossus muscle activity in neonatal rats. J Physiol. 2004, 557 (Pt 1): 13-18.PubMedPubMedCentralCrossRef
13.
go back to reference Kim CS, McNamara MC, Lauder JM, Lawson EE: Immunocytochemical detection of serotonin content in raphe neurons of newborn and young adult rabbits before and after acute hypoxia. Int J Dev Neurosci. 1994, 12: 499-505.PubMedCrossRef Kim CS, McNamara MC, Lauder JM, Lawson EE: Immunocytochemical detection of serotonin content in raphe neurons of newborn and young adult rabbits before and after acute hypoxia. Int J Dev Neurosci. 1994, 12: 499-505.PubMedCrossRef
14.
go back to reference Erickson JT, Millhorn DE: Hypoxia and electrical stimulation of carotid sinus nerve induce Fos-like immunoreactivity within catecholaminergic and serotoninergic neurons of the rat brainstem. J Comp Neurol. 1994, 348: 161-182.PubMedCrossRef Erickson JT, Millhorn DE: Hypoxia and electrical stimulation of carotid sinus nerve induce Fos-like immunoreactivity within catecholaminergic and serotoninergic neurons of the rat brainstem. J Comp Neurol. 1994, 348: 161-182.PubMedCrossRef
15.
go back to reference Ohliger-Frerking P, Horwitz BA, Horowitz JM: 5-HT dorsal raphe neurons from obese zucker rats are hyperexcitable. Neuroscience. 2003, 120: 627-634.PubMedCrossRef Ohliger-Frerking P, Horwitz BA, Horowitz JM: 5-HT dorsal raphe neurons from obese zucker rats are hyperexcitable. Neuroscience. 2003, 120: 627-634.PubMedCrossRef
16.
go back to reference McNamara MC, Gingras-Leatherman JL, Lawson EE: Effect of hypoxia on brainstem concentration of biogenic amines in postnatal rabbits. Brain Res. 1986, 390 (2): 253-258.PubMedCrossRef McNamara MC, Gingras-Leatherman JL, Lawson EE: Effect of hypoxia on brainstem concentration of biogenic amines in postnatal rabbits. Brain Res. 1986, 390 (2): 253-258.PubMedCrossRef
17.
go back to reference Wang W, Similowski T, Sériès F: Interaction between genioglossus and diaphragm responses to transcranial magnetic stimulation in awake humans. Exp Physiol. 2007, 92: 739-747.PubMedCrossRef Wang W, Similowski T, Sériès F: Interaction between genioglossus and diaphragm responses to transcranial magnetic stimulation in awake humans. Exp Physiol. 2007, 92: 739-747.PubMedCrossRef
18.
go back to reference Nattie EE, Li A, Richerson GB, Lappi DA: Medullary 5-HT neurons and adjacent neurons that express neurokinin-1 receptors are both involved in chemoreception in vivo. J Physiol. 2004, 556 (Pt 1): 235-253.PubMedPubMedCentralCrossRef Nattie EE, Li A, Richerson GB, Lappi DA: Medullary 5-HT neurons and adjacent neurons that express neurokinin-1 receptors are both involved in chemoreception in vivo. J Physiol. 2004, 556 (Pt 1): 235-253.PubMedPubMedCentralCrossRef
19.
go back to reference Sood S, Raddatz E, Liu X, Liu H, Horner RL: Inhibition of 5-HT medullary raphe obscurus neurons suppresses genioglossus and diaphragm activities in anesthetized but conscious rats. J Appl Physiol. 2006, 100: 1807-1821.PubMedCrossRef Sood S, Raddatz E, Liu X, Liu H, Horner RL: Inhibition of 5-HT medullary raphe obscurus neurons suppresses genioglossus and diaphragm activities in anesthetized but conscious rats. J Appl Physiol. 2006, 100: 1807-1821.PubMedCrossRef
20.
go back to reference Dias MB, Nucci TB, Marqatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG: Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol. 2007, 103: 1780-1788.PubMedCrossRef Dias MB, Nucci TB, Marqatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG: Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol. 2007, 103: 1780-1788.PubMedCrossRef
21.
go back to reference Paxinos G, Watson C: The Brain in Stereotaxic Coordinates. 2007, San Diego, CA: Academic, 6 Paxinos G, Watson C: The Brain in Stereotaxic Coordinates. 2007, San Diego, CA: Academic, 6
22.
23.
go back to reference Civardi C, Naldi P, Cantello R: Cortico-motoneurone excitability in patients with obstructive sleep apnoea. J Sleep Res. 2004, 13: 159-163.PubMedCrossRef Civardi C, Naldi P, Cantello R: Cortico-motoneurone excitability in patients with obstructive sleep apnoea. J Sleep Res. 2004, 13: 159-163.PubMedCrossRef
24.
go back to reference Ling LM, Fuller DD, Bach KB, Kinkead R, Olson EB, Mitchell GS: Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. J Neurosci. 2001, 21: 5381-5388.PubMed Ling LM, Fuller DD, Bach KB, Kinkead R, Olson EB, Mitchell GS: Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. J Neurosci. 2001, 21: 5381-5388.PubMed
25.
go back to reference Cao Y, Liu C, Ling LM: Glossopharyngeal long-term facilitation requires serotonin 5-HT2 and NMDA receptors in rats. Respir Physiol Neurobiol. 2010, 170 (2): 164-172.PubMedPubMedCentralCrossRef Cao Y, Liu C, Ling LM: Glossopharyngeal long-term facilitation requires serotonin 5-HT2 and NMDA receptors in rats. Respir Physiol Neurobiol. 2010, 170 (2): 164-172.PubMedPubMedCentralCrossRef
26.
go back to reference Li YQ, Takada M, Mizuno N: The site of origin of serotoninergic afferent fibers in the trigeminal motor, facial, and hypoglossus nuclei in the rat. Neurosci Res. 1993, 17 (4): 307-313.PubMedCrossRef Li YQ, Takada M, Mizuno N: The site of origin of serotoninergic afferent fibers in the trigeminal motor, facial, and hypoglossus nuclei in the rat. Neurosci Res. 1993, 17 (4): 307-313.PubMedCrossRef
27.
go back to reference Gargaglioni LH, Coimbra NC, Branco LG: The nucleus raphe magnus modulates hypoxia-induced hyperventilation but not anapyrexia in rats. Neurosci Lett. 2003, 347 (2): 121-125.PubMedCrossRef Gargaglioni LH, Coimbra NC, Branco LG: The nucleus raphe magnus modulates hypoxia-induced hyperventilation but not anapyrexia in rats. Neurosci Lett. 2003, 347 (2): 121-125.PubMedCrossRef
28.
go back to reference Simonyan K, Jurgens U: Afferent subcortical connections into the motor cortical larynx area in the rhesus monkey. Neuroscience. 2005, 130 (1): 119-131.PubMedCrossRef Simonyan K, Jurgens U: Afferent subcortical connections into the motor cortical larynx area in the rhesus monkey. Neuroscience. 2005, 130 (1): 119-131.PubMedCrossRef
29.
go back to reference Horner RL: The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea. Respir Res. 2001, 2: 286-294.PubMedPubMedCentralCrossRef Horner RL: The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea. Respir Res. 2001, 2: 286-294.PubMedPubMedCentralCrossRef
30.
go back to reference Horner RL: Emerging principles and neural substrates underlying tonic sleep-state-dependent influences on respiratory motor activity. Philos Trans R Soc Lond B Biol Sci. 2009, 364 (1529): 2553-2564.PubMedPubMedCentralCrossRef Horner RL: Emerging principles and neural substrates underlying tonic sleep-state-dependent influences on respiratory motor activity. Philos Trans R Soc Lond B Biol Sci. 2009, 364 (1529): 2553-2564.PubMedPubMedCentralCrossRef
31.
go back to reference Grace KP, Liu H, Horner RL: 5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity. J Neurosci. 2012, 32: 1622-1633.PubMedCrossRef Grace KP, Liu H, Horner RL: 5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity. J Neurosci. 2012, 32: 1622-1633.PubMedCrossRef
32.
go back to reference Da Silva GS, Giusti H, Benedetti M, Dias MB, Gargaglioni LH, Branco LG, Glass ML: 5-HT neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia. Pflugers Arch Eur J Phy. 2011, 462 (3): 407-418.CrossRef Da Silva GS, Giusti H, Benedetti M, Dias MB, Gargaglioni LH, Branco LG, Glass ML: 5-HT neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia. Pflugers Arch Eur J Phy. 2011, 462 (3): 407-418.CrossRef
33.
go back to reference Da Silva GS, Giusti H, Castro OW, Garcia-Cairasco N, Gargaglioni LH, Branco LG, Glass ML: 5-HT neurons in the nucleus raphe obscurus are not involved in the ventilatory and thermoregulatory responses to hypoxia in adult rats. Respir Physiol Neurobiol. 2013, 187 (2): 139-148.PubMedCrossRef Da Silva GS, Giusti H, Castro OW, Garcia-Cairasco N, Gargaglioni LH, Branco LG, Glass ML: 5-HT neurons in the nucleus raphe obscurus are not involved in the ventilatory and thermoregulatory responses to hypoxia in adult rats. Respir Physiol Neurobiol. 2013, 187 (2): 139-148.PubMedCrossRef
Metadata
Title
Raphe serotonergic neurons modulate genioglossus corticomotor activity in intermittent hypoxic rats
Authors
Jiao Su
Wei Wang
Longfeng Sun
Ting Li
Delei Kong
Jian Kang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-15-76

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