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Abnormalities of the Brainstem Serotonergic System in the Sudden Infant Death Syndrome: A Review

  • Perspectives in Pediatric Pathology
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Pediatric and Developmental Pathology

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References

  1. Willinger M, James S, Catz C. Defining the SIDS: deliberations of an expert panel convened by the National Institute of Child Health and Development. Pediatr Pathol 1991;11:677–684

    PubMed  CAS  Google Scholar 

  2. Matthews TJ, MacDorman MF, et al. Infant Mortality Statistics From the 1999 Period Linked Birth/Infant Death Data Set. Hyattsville, MD: National Center for Health Statistics, 2002

    Google Scholar 

  3. Iyasu S, Randall LL, Welty TK, et al. Risk factors for sudden infant death syndrome among Northern Plains Indians. JAMA 2002;288:2717–2723

    Article  PubMed  Google Scholar 

  4. Hauck FR. Changing epidemiology. In: Byard RW, Krous HF, eds. Sudden Infant Death Syndrome: Problems, Progress and Possibilities. London: Arnold, 2001;31–57

    Google Scholar 

  5. Kinney HC, Randall LL, Sleeper LA, et al. Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome. J Neuropathol Exp Neurol 2003;62:1178–1191

    PubMed  CAS  Google Scholar 

  6. Narita N, Narita M, Takashima S, et al. Serotonin transporter gene variation as a risk factor for sudden infant death syndrome in the Japanese population. Pediatrics 2001;107:690–692

    Article  PubMed  CAS  Google Scholar 

  7. Weese-Mayer DE, Zhou L, Berry-Kravas EM, et al. Association of the serotonin transporter gene with sudden infant death syndrome. Am J Genet 2003;122A:238–245

    Google Scholar 

  8. Weese-Mayer DE, Zhou L, Berry-Kravis EM, et al. Association of the serotonin transporter gene with sudden infant death syndrome: a haplotype analysis. Am J Med Genet 2003;122A:238–245

    Article  Google Scholar 

  9. Summers AM, Summers CW, Drucker DB, et al. Association of the IL-10 genotype with sudden infant death syndrome. Hum Immunol 2000;61:1270–1273

    Article  PubMed  CAS  Google Scholar 

  10. Panigrahy A, Filiano JJ, Sleeper LA, et al. Decreased serotonergic receptor binding in rhombic lip-derived regions of the medulla oblongata in the sudden infant death syndrome. J Neuropathol Exp Neurol 2000;59:377–384

    PubMed  CAS  Google Scholar 

  11. Mansouri J, Panigrahy A, Filiano JJ, et al. Alpha2 receptor binding in the medulla oblongata in the sudden infant death syndrome. J Neuropathol Exp Neurol 2001;60:141–146

    PubMed  CAS  Google Scholar 

  12. Nachmanoff DB, Panigrahy A, Filiano JJ, et al. Brainstem 3H-nicotine receptor binding in the sudden infant death syndrome. J Neuropathol Exp Neurol 1998;57:1018–1025

    PubMed  CAS  Google Scholar 

  13. Kinney HC, Filiano JJ, Sleeper LA, et al. Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome. Science 1995;269:1446–1450

    PubMed  CAS  Google Scholar 

  14. Panigrahy A, Filiano JJ, Sleeper LA, et al. Decreased kainate receptor binding in the arcuate nucleus of the sudden infant death syndrome. J Neuropathol Exp Neurol 1997;56:1253–1261

    PubMed  CAS  Google Scholar 

  15. Kinney HC, Filiano JJ, Assmann SF, et al. Tritiated-naloxone binding to brainstem opioid receptors in the sudden infant death syndrome. J Auton Nerv Syst 1998;69:156–163

    Article  PubMed  CAS  Google Scholar 

  16. Kinney HC, Filiano JJ, White WF. Medullary serotonergic network deficiency in the sudden infant death syndrome: review of a 15-year study of a single dataset. J Neuropathol Exp Neurol 2001;60:228–247

    PubMed  CAS  Google Scholar 

  17. Schechtman VL, Lee MY, Wilson AJ, et al. Dynamics of respiratory patterning in normal infants and infants who subsequently died of the sudden infant death syndrome. Pediatr Res 1996;40:571–577

    PubMed  CAS  Google Scholar 

  18. Schechtman VL, Harper RM, Kluge KA, et al. Heart rate variation in normal infants and victims of the sudden infant death syndrome. Early Hum Dev 1989;19:167–181

    Article  PubMed  CAS  Google Scholar 

  19. Kato I, Franco P, Groswasser J, et al. Incomplete arousal processes in infants who were victims of sudden death. Am J Respir Crit Care Med 2003;168:1298–1303

    Article  PubMed  Google Scholar 

  20. Groswasser J, Simo T, Schillet S, et al. Reduced arousals following obstructive apneas in infants sleeping prone. Pediatr Res 2001;49:402–406

    PubMed  CAS  Google Scholar 

  21. Franco P, Lipshutz W, Valente F, et al. Decreased arousals in infants who sleep with the face covered by bedclothes. Pediatrics 2002;109:1112–1117

    Article  PubMed  Google Scholar 

  22. Franco P, Lipshut W, Valente F, et al. Cardiac autonomic characteristics in infants sleeping with their face covered by bedclothes. J Sleep Res 2003;2:125–132

    Google Scholar 

  23. Horne RS, Ferens D, Watts AM, et al. The prone sleeping position impairs arousability in term infants. J Pediatr 2001;138:811–816

    PubMed  CAS  Google Scholar 

  24. Galland BC, Reeves G, Taylor BJ, Bolton DP. Sleep position, autonomic function, and arousal. Arch Dis Child 1998;78:F189–F194

    CAS  Google Scholar 

  25. Chong A, Murphy N, Matthews T. Effect of prone sleeping on circulatory control in infants. Arch Dis Child 2000;82:253–256

    Article  PubMed  CAS  Google Scholar 

  26. Naeye RL. Brain stem and adrenal abnormalities in the sudden infant death syndrome. Am J Clin Pathol 1966;66:526–539

    Google Scholar 

  27. Kinney HC, Burger PC, Harrell FE Jr, Hudson RP Jr. ‘Reactive gliosis’ in the medulla oblongata of victims of the sudden infant death syndrome. Pediatrics 1983;72:181–187

    PubMed  CAS  Google Scholar 

  28. Takashima S, Armstrong D, Becker LE, Bryan C. Cerebral hypoperfusion in the sudden infant death syndrome? Brainstem gliosis and vascular supply. Ann Neurol 1978;4:257–262

    Article  PubMed  CAS  Google Scholar 

  29. Filiano JJ, Kinney HC. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate 1994;65:194–197

    PubMed  CAS  Google Scholar 

  30. Kinney HC, Paterson DS. The sudden infant death syndrome. In: Golden JA, Harding B, eds. Pathology and Genetics: Acquired and Inherited Disease of the Developing Nervous System. Basel: ISN Neuropathology Press, 2004;194–203

    Google Scholar 

  31. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology 1999;38:1083–1152

    Article  PubMed  CAS  Google Scholar 

  32. Blakely RD, Bauman AL. Biogenic amine transporters: regulation in flux. Curr Opin Neurobiol 2000;10:328–336

    Article  PubMed  CAS  Google Scholar 

  33. Kelai S, Aissi F, Lesch KP, et al. Alcohol intake after serotonin transporter inactivation in mice. Alcohol Alcohol 2003;38:386–389

    PubMed  CAS  Google Scholar 

  34. Awtry TL, Werling LL. Acute and chronic effects of nicotine on serotonin uptake in prefrontal cortex and hippocampus in rats. Synapse 2003;50:206–211

    Article  PubMed  CAS  Google Scholar 

  35. Mossner R, Heils A, Stober G, et al. Enhancement of serotonin transporter function by tumor necrosis factor alpha but not be interleukin-6. Neurochem Int 1998;33:251–254

    PubMed  CAS  Google Scholar 

  36. Törk I, Hornung JP. Raphe nuclei and the 5-HT system. In: Paxinos G, ed. The Human Nervous System. San Diego: Academic Press, 1990;1001–1022

    Google Scholar 

  37. Hornung JP. The human raphe nuclei and the serotonergic system. J Chem Neuroanat 2003;26:331–343

    Article  PubMed  CAS  Google Scholar 

  38. McGinty D, Harper RM. Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res 1976;101:569–575

    Article  PubMed  CAS  Google Scholar 

  39. Trulson ME, Jacobs BJ. Raphe unit activity in freely moving cats: correlation with the level of behavioral arousal. Brain Res 1979;163:135–150

    Article  PubMed  CAS  Google Scholar 

  40. Mason P. Contributions of the medullary raphe and ventromedial reticular region to pain modulation and other homeostatic functions. Annu Rev Neurosci 2001;24:737–777

    Article  PubMed  CAS  Google Scholar 

  41. Lovick TA. The medullary raphe nuclei: a system for integration and gain control in autonomic and somatomotor responsiveness? Exp Physiol 1997;82:31–41

    PubMed  CAS  Google Scholar 

  42. Morrison SF. Differential control of sympathetic outflow. Am J Physiol Regul Integr Comp Physiol 2001;281:R683–R698

    PubMed  CAS  Google Scholar 

  43. Azmitia EC. Serotonin neurons, neuroplasticity, and homeostasis of neural tissue. Neuropsychopharmacology 1999;21:33S–45S

    PubMed  CAS  Google Scholar 

  44. Jacobs BL, Wilkinson LO, Fornal CA. The role of brain serotonin. A neurophysiologic perspective. Neuropsychopharmacology 1990;3:473–479

    PubMed  CAS  Google Scholar 

  45. Smith JC, Ellenberger HH, Ballanyi K, et al. Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 1991;254:726–729

    PubMed  CAS  Google Scholar 

  46. Gray P, Janczewski WA, Mellen N, et al. Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons. Nat Neurosci 2001;4:927–930

    Article  PubMed  CAS  Google Scholar 

  47. Erickson JT, Millhorn DE. Hypoxia and electrical stimulation of the carotid sinus nerve induce Fos-like immunoreactivity within catecholaminergic and serotonergic neurons of the rat brainstem. J Comp Neurol 1994;348:161–182

    Article  PubMed  CAS  Google Scholar 

  48. Martin-Curo FJ, Fornal CA, Metzler CW, Jacobs BL. Insulin-induced hypoglycemia decreases single-unit activity of serotonergic medullary raphe neurons in freely moving cats: relationship to sympathetic and motor output. Eur J Neurosci 2002;16:722–734

    Google Scholar 

  49. Bradley SR, Pieribone VA, Wang W, et al. Chemosensitive serotonergic neurons are closely associated with large medullary arteries. Nat Neurosci 2002;5:401–402

    Article  PubMed  CAS  Google Scholar 

  50. Wang W, Tiwari JK, Bradley SR, et al. Acidosis-stimulated neurons of the medullary raphe are serotonergic. J Neurophysiol 2001;85:224–235

    Google Scholar 

  51. Bou-Fiores C, Lajard A, Monteau R, et al. Abnormal phrenic motoneuron activity and morphology in neonatal monoamine oxidase A-deficient transgenic mice: possible role of a serotonin excess. J Neurosci 2000;10:4646–4656

    Google Scholar 

  52. Hokfelt T, et al. Multiple messengers in descending serotonin neurons: localization and functional implications. J Chem Neuroanat 2000;18:75–86

    PubMed  CAS  Google Scholar 

  53. Monteau R, Morin D, Hennequin S, et al. Differential effects of serotonin on respiratory activity in hypoglossal and cervical motoneurons: an in vitro study on the newborn rat. Neurosci Lett 1990;111:127–132

    Article  PubMed  CAS  Google Scholar 

  54. Pena F, Ramirez JM. Endogenous activation of serotonin-2A receptors is required for respiratory rhythm generation in vitro. J Neurosci 2002;22:11055–11064

    PubMed  CAS  Google Scholar 

  55. Raul L. Serotonin2 receptors in the nucleus tractus solitarius: characterization and role in the baroreceptor arc. Cell Mol Neurobiol 2003;23:709–746

    Article  PubMed  CAS  Google Scholar 

  56. Gao K, Mason P. The discharge of a subset of serotonergic raphe magnus neurons is influenced by baroreceptor input. Brain Res 2001;900:306–313

    Article  PubMed  CAS  Google Scholar 

  57. Messier ML, Li A, Nattie EE. Inhibition of medullary raphe serotonergic neurons has age-dependent effect on the CO2 response in newborn piglets. J Appl Physiol 2004;96:1909–1919

    Article  PubMed  Google Scholar 

  58. Pelaez NM. Schreihofer AM, Guyenet PG. Decompensated hemorrhage activates serotonergic neurons in the subependymal parapyramidal region of the rat medulla. Am J Physiol Regul Integr Comp Physiol 2002;283:R688–R697

    PubMed  CAS  Google Scholar 

  59. Hilaire G, Morin D, Lajard AM, Monteau R. Changes in serotonin metabolism may elicit obstructive apnoea in the newborn rat. J Physiol 1993;446:367–381

    Google Scholar 

  60. Nagai M. The role of serotonergic system in body temperature regulation. Physiol Res 1992;41:65–69

    PubMed  CAS  Google Scholar 

  61. Holtmann JR, Dick TE, Berger AJ. Serotonin-mediated excitation of recurrent laryngeal and phrenic motoneurons evoked by stimulation of the raphe obscurus. Brain Res 1987;417:12–20

    Google Scholar 

  62. Poets CF, Meny RG, Chobanian MR, Bonofiglo RE. Gasping and other cardiorespiratory patterns during sudden infant death. Pediatr Res 1999;45:350–354

    PubMed  CAS  Google Scholar 

  63. Sridar R, Thach BT, Kelly DH, Henslee JA. Characterization of successful and failed autoresuscitation in human infants, including those who die of SIDS. Pediatr Pulmonol 2003;36:113–122

    Google Scholar 

  64. Filiano JJ, Kinney HC. Arcuate nucleus hypoplasia in the sudden infant death syndrome. J Neuropathol Exp Neurol 1992;51:394–403

    PubMed  CAS  Google Scholar 

  65. Filiano JJ, Choi JC, Kinney HC. Candidate cell populations for respiratory chemosensitive fields in the human infant medulla. J Comp Neurol 1990;293:448–495

    Article  PubMed  CAS  Google Scholar 

  66. Biondo B, Lavezzi A, Tosi D, et al. Delayed neuronal maturation of the medullary arcuate nucleus in sudden infant death syndrome. Acta Neuropathol 2003;106:545–551

    Article  PubMed  Google Scholar 

  67. Matturri L, Biondo B, Mercurio P, Rossi L. Severe hypoplasia of medullary arcuate nucleus: quantitative analysis in sudden infant death syndrome. Acta Neuropathol 2000;99:371–375

    Article  PubMed  CAS  Google Scholar 

  68. Matturri L, Biondo B, Suarez-Mier MP, Rossi L. Brain stem lesions in the sudden infant death syndrome: variability in the hypoplasia of the arcuate nucleus. Acta Neuropathol 2002;104:12–20

    PubMed  CAS  Google Scholar 

  69. Folgering H, Kuyper F, Kille JF. Primary alveolar hypoventilation (Ondine’s curse syndrome) in an infant without external arcuate nucleus. Case report. Bull Eur Physiopathol Resp 1979;15:659–665

    CAS  Google Scholar 

  70. Zec N, Filiano JJ, Panigrahy A, et al. Developmental changes in [3H]-lysergic acid diethylamide ([3H]LSD) binding in serotonin receptors in the human brainstem. J Neuropathol Exp Neurol 1996;55:114–126

    PubMed  CAS  Google Scholar 

  71. Paterson DS, Belliveau RA, Trachtenberg F, Kinney HC. Differential development of 5-HT receptor and the serotonin transporter binding in the human infant medulla. J Comp Neurol 2004;47:221–231

    Google Scholar 

  72. Mulkey DK, Stornella RL, Weston MC, et al. Respiratory control by ventricular surface chemoreceptor neurons in rats. Nat Neurosci 2004;7:1360–1369

    Article  PubMed  CAS  Google Scholar 

  73. Zec N, Filiano JJ, Kinney HC. Anatomic relationships of the human arcuate nucleus of the medulla: a DiI labeling study. J Neuropathol Exp Neurol 1997;56:509–522

    PubMed  CAS  Google Scholar 

  74. Zec N, Kinney HC. Anatomic relationships of the human nucleus paragigantocellularis lateralis: a DiI labeling study. Auton Neurosci 2001;105:110–124

    Google Scholar 

  75. Zec N, Kinney HC. Anatomic relationships of the human nucleus of the solitary tract: a DiI labeling study. Auton Neurosci 2003;105:131–144

    PubMed  Google Scholar 

  76. Katz LC, Shatz CJ. Synaptic activity and the construction of cortical circuits. Science 1996;274:1133–1138

    Article  PubMed  CAS  Google Scholar 

  77. Penn AA, Shatz CJ. Brain waves and brain wiring: the role of endogeneous and sensory driven neural activity. Pediatr Res 1999;45:442–458

    Google Scholar 

  78. Lidov H, Molliver M. Immunohistochemical study of the development of serotonergic neurons in the rat CNS. Brain Res Bull 1982;9:559–604

    Article  PubMed  CAS  Google Scholar 

  79. Rubenstein JL. Development of serotonergic neurons and their projections. Biol Psychiatry 1998;44:145–150

    Article  PubMed  CAS  Google Scholar 

  80. Buznikov GA, Lambert HW, Lauder JM. Serotonin and serotonin-like substances as regulators in early embryogenesis and morphogenesis. Cell Tissue Res 2001;305:177–186

    Article  PubMed  CAS  Google Scholar 

  81. Sundstrom E, Kolare S, Souverbie F, et al. Neurochemical differentiation of human bulbospinal monoaminergic neurons during the first trimester. Brain Res Dev Brain Res 1993;75:1–12

    PubMed  CAS  Google Scholar 

  82. Faber KM, Haring JH. Synaptogenesis in the postnatal rat fascia dentate is influenced by 5-HT1a receptor activation. Brain Res Dev Brain Res 1999;114:245–252

    PubMed  CAS  Google Scholar 

  83. Haydon PG, McCobb DP, Kater SB. The regulation of neurite outgrowth, growth cone motility, and electrical synaptogenesis by serotonin. J Neurobiol 1987;18:197–215

    Article  PubMed  CAS  Google Scholar 

  84. Mazer C, Muneyyirci J, Taheny K, et al. Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible cognitive model of neurodevelopmental disorders with cognitive deficits. Brain Res 1997;760:68–73

    Article  PubMed  CAS  Google Scholar 

  85. Kondoh M, Shiga T, Okado N. Regulation of dendrite formation of Purkinje cells by serotonin through serotonin1A and serotonin2A receptors in culture. Neurosci Res 2004;48:101–109

    Article  PubMed  CAS  Google Scholar 

  86. Sood S, Liu X, Liu H, et al. 5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats. Respir Physiol Neurobiol 2003;138:205–221

    Article  PubMed  CAS  Google Scholar 

  87. Talley EM, Sadr NN, Bayliss DA. Postnatal development of serotonergic innervation, 5-HT1A receptor expression, and 5-HT responses in rat motoneurons. J Neurosci 1997;17:4473–4485

    PubMed  CAS  Google Scholar 

  88. Nattie EE, Kinney HC. Nicotine, serotonin, and sudden infant death syndrome (editorial). Am J Resp Crit Care Med 2002;166:1530–1531

    Article  PubMed  Google Scholar 

  89. Zhou FC, Sari Y, Zhang JK, et al. Prenatal alcohol exposure retards the migration and development of serotonin neurons in fetal C57BL mice. Dev Brain Res 2001;126:145–155

    Article  Google Scholar 

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Kinney, H.C. Abnormalities of the Brainstem Serotonergic System in the Sudden Infant Death Syndrome: A Review. Pediatr Dev Pathol 8, 507–524 (2005). https://doi.org/10.1007/s10024-005-0067-y

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