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Myo-inositol Effects on the Developing Respiratory Neural Control System

  • Peter M. MacFarlaneEmail author
  • Juliann M. Di Fiore
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1071)

Abstract

Myo-inositol is a highly abundant stereoisomer of the inositol family of sugar alcohols and forms the structural basis for a variety of polyphosphate derivatives including second messengers and membrane phospholipids. These derivatives regulate numerous cell processes including gene transcription, membrane excitability, vesicular trafficking, intracellular calcium signaling, and neuronal growth and development. Myo-inositol can be formed endogenously from the breakdown of glucose, is found in a variety of foods including breastmilk and is commercially available as a nutritional supplement. Abnormal myo-inositol metabolism has been shown to underlie the pathophysiology of a variety of clinical conditions including Down Syndrome, traumatic brain injury, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome (RDS). Several animal studies have shown that myo-inositol may play a critical role in development of both the central and peripheral respiratory neural control system; a notable example is the neonatal apnea and respiratory insufficiency that manifests in a mouse model of myo-inositol depletion, an effect that is also postnatally lethal. This review focuses on myo-inositol (and some of its derivatives) and how it may play a role in respiratory neural control; we also discuss clinical evidence demonstrating a link between serum myo-inositol levels and the incidence of intermittent hypoxemia (IH) events (a surrogate measure of apnea of prematurity (AOP)) in preterm infants. Further, there are both animal and human infant studies that have demonstrated respiratory benefits following supplementation with myo-inositol, which highlights the prospects that nutritional requirements are important for appropriate development and maturation of the respiratory system.

Keywords

Myo-inositol Respiratory neural development Control of breathing 

Notes

Acknowledgements

P.M.M. and J.M.D. are supported by the Gerber Foundation. Reference# 1082-4005.

References

  1. Barraco RA, Phillis JW, Simpson LL (1989) Cardiorespiratory effects of inositol hexakisphosphate following microinjections into the nucleus tractus solitarii. Eur J Pharmacol 173(1):75–84CrossRefGoogle Scholar
  2. Berridge MJ (1987) Inositol trisphosphate and diacylgycerol: two interacting second messengers. Ann Rev Biochem 56:159–193CrossRefGoogle Scholar
  3. Berry GT, Mallee JJ, Kwon HM, Rim JS, Mulla WR, Muenke M, Spinner NB (1995) The human osmoregulatory Na+/myo-inositol cotransporter gene (SLC5A3): molecular cloning and localization to chromosome 21. Genomics 25(2):507–513CrossRefGoogle Scholar
  4. Berry GT, Wu S, Buccafusca R, Ren J, Gonzales LW, Ballard PL, Golden JA, Stevens MJ, Greer JJ (2003) Loss of murine Na+/myo-inositol cotransporter leads to brain myo-inositol depletion and central apnea. J Biol Chem 278(20):18297–18302CrossRefGoogle Scholar
  5. Buccafusca R, Venditti CP, Kenyon LC, Johanson RA, Van Bockstaele E, Ren J, Pagliardini S, Minarcik J, Golden JA, Coady MJ, Greer JJ, Berry GT (2008) Characterization of the null murine sodium/myo-inositol cotransporter 1 (Smit1 or Slc5a3) phenotype: myo-inositol rescue is independent of expression of its cognate mitochondrial ribosomal protein subunit 6 (Mrps6) gene and of phosphatidylinositol levels in neonatal brain. Mol Genet Metab 95(1–2):81–95CrossRefGoogle Scholar
  6. Chau JF, Lee MK, Law JW, Chung SK, Chung SS (2005) Sodium/myo-inositol cotransporter-1 is essential for the development and function of the peripheral nerves. FASEB J 19(13):1887–1889CrossRefGoogle Scholar
  7. Chen J, He L, Dinger B, Fidone S (2000) Cellular mechanisms involved in rabbit carotid body excitation elicited by endothelin peptides. Respir Physiol 121(1):13–23CrossRefGoogle Scholar
  8. Collins BM, McCoy AJ, Kent HM, Evans PR, Owen DJ (2002) Molecular architecture and functional model of the endocytic AP2 complex. Cell 109(4):523–535CrossRefGoogle Scholar
  9. Conrad MS, Sutton BP, Larsen R, Van Alstine WG, Johnson RW (2015) Early postnatal respiratory viral infection induces structural and neurochemical changes in the neonatal piglet brain. Brain Behav Immun 48:326–335CrossRefGoogle Scholar
  10. Crowder EA, Saha MS, Pace RW, Zhang H, Prestwich GD, Del Negro CA (2007) Phosphatidylinositol 4,5-bisphosphate regulates inspiratory burst activity in the neonatal mouse preBötzinger complex. J Physiol 582(Pt 3):1047–1058CrossRefGoogle Scholar
  11. De Camilli P, Emr SD, McPherson PS, Novick P (1996) Phosphoinositides as regulators in membrane traffic. Science 271(5255):1533–1539CrossRefGoogle Scholar
  12. Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, Walsh M, Finer N, Martin RJ (2010) A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr 157(1):69–73CrossRefGoogle Scholar
  13. Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA, Martin RJ (2012) Support study group of Eunice Kennedy Shriver national institute of child health and human development neonatal research network. Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. J Pediatr 161(6):1047–1052CrossRefGoogle Scholar
  14. Godfrey DA, Hallcher LM, Laird MH, Matschinsky FM, Sherman WR (1982) Distribution of myo-inositol in the cat cochlear nucleus. J Neurochem 38(4):939–947CrossRefGoogle Scholar
  15. Greer JJ, Allan DW, Martin-Carabello M, Lemke RP (1999) An overview of phrenic nerve and diaphragm muscle development in the perinatal rat. J Appl Physiol 86:779–786CrossRefGoogle Scholar
  16. Hallman M, Bry K, Hoppu K, Lappi M, Pohjavuori M (1992) Inositol supplementation in premature infants with respiratory distress syndrome. N Engl J Med 326(19):1233–1239CrossRefGoogle Scholar
  17. Hanley MR, Jackson TR, Vallejo M, Patterson SI, Thastrup O, Lightman S, Rogers J, Henderson G, Pini A (1988) Neural function: metabolism and actions of inositol metabolites in mammalian brain. Philos Trans R Soc Lond B Biol Sci 320(1199):381–398Google Scholar
  18. Harlan JE, Hajduk PJ, Yoon HS, Fesik SW (1994) Pleck-strin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature 371(6493):168–170CrossRefGoogle Scholar
  19. He L, Chen J, Dinger B, Fidone S (1996) Endothelin modulates chemoreceptor cell function in mammalian carotid body. Adv Exp Med Biol 410:305–311CrossRefGoogle Scholar
  20. Hofstetter AO, Legnevall L, Herlenius E, Katz-Salamon M (2008) Cardiorespiratory development in extremely preterm infants: vulnerability to infection and persistence of events beyond term-equivalent age. Acta Paediatr 97:285–292CrossRefGoogle Scholar
  21. Holub BJ (1986) Metabolism and function of myo-inositol and inositol phospholipids. Ann Rev Nutr 6:563–597CrossRefGoogle Scholar
  22. Kumar P, Prabhakar NR (2012) Peripheral chemoreceptors: function and plasticity of the carotid body. Compr Physiol 2(1):141–219PubMedPubMedCentralGoogle Scholar
  23. McQueen DS, Dashwood MR, Cobb VJ, Bond SM, Marr CG, Spyer KM (1995) Endothelins and rat carotid body: autoradiographic and functional pharmacological studies. J Auton Nerv Syst 53:115–125CrossRefGoogle Scholar
  24. Moratalla R, Vallejo M, Lightman SL (1988) Vasopressin stimulates inositol phospholipid metabolism in rat medulla oblongata in vivo. Brain Res 450(1–2):398–402CrossRefGoogle Scholar
  25. Ogimoto G, Yudowski GA, Barker CJ, Köhler M, Katz AI, Féraille E, Pedemonte CH, Berggren PO, Bertorello AM (2000) G protein-coupled receptors regulate Na+,K+-ATPase activity and endocytosis by modulating the recruitment of adaptor protein 2 and clathrin. Proc Natl Acad Sci 7(7):3242–3247CrossRefGoogle Scholar
  26. Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, Solimano A, Nelson H (2015) Canadian oxygen trial investigators. Association between intermittent hypoxemia or bradycardia and late death or disability in extremely preterm infants. JAMA 314(6):595–603CrossRefGoogle Scholar
  27. Pokorsky M, Strosznajder R (1993) PO2-dependence of phospholipase C in the cat carotid body. Adv Exp Med Biol 337:191–195CrossRefGoogle Scholar
  28. Raman L, Tkac I, Ennis K, Georgieff MK, Gruetter R, Rao R (2005) In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus. Res Rep 156:202–209CrossRefGoogle Scholar
  29. Rigual R, Cachero MT, Rocher A, González C (1999) Hypoxia inhibits the synthesis of phosphoinositides in the rabbit carotid body. Pflugers Arch 437(6):839–845CrossRefGoogle Scholar
  30. Roll P, Massacrier A, Pereira S, Robaglia-Schlupp A, Cau P, Szepetowski P (2002) New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families. Gene 285:141–148CrossRefGoogle Scholar
  31. Serra A1, Brozoski D, Hedin N, Franciosi R, Forster HV (2001) Mortality after carotid body denervation in rats. J Appl Physiol (1985) 91(3):1298–1306CrossRefGoogle Scholar
  32. Stock C, Teyssier G, Pichot V, Goffaux P, Barthelemy JC, Patural H (2010) Autonomic dysfunction with early respiratory syncytial virus-related infection. Auton Neurosci 156:90–95CrossRefGoogle Scholar
  33. Vallejo M, Jackson T, Lightman S, Hanley MR (1987) Occurrence and extracellular actions of inositol pentakis- and hexakisphosphate in mammalian brain. Nature 330(6149):656–658CrossRefGoogle Scholar
  34. Wurmser AE, Gary JD, Emr SD (1999) Phosphoinositide 3-kinases and their FYVE domain-containing effectors as regulators of vacuolar/lysosomal membrane trafficking pathways. J Biol Chem 274(14):9129–9132CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Case Western Reserve University, Rainbow Babies & Children’s HospitalClevelandUSA

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