Alteration of Serotonergic Receptors in the Brain Stems of Human Patients with Respiratory Disorders

Y. Ozawa; N. Okado

doi:10.1055/s-2002-33678

Neuropediatrics, Table of Contents

Neuropediatrics 2002; 33(3): 142-149
DOI: 10.1055/s-2002-33678

Original Article

Georg Thieme Verlag Stuttgart · New York

Alteration of Serotonergic Receptors in the Brain Stems of Human Patients with Respiratory Disorders

Y. Ozawa¹ , N. Okado²

¹ Department of Neonatology, Toho University School of Medicine, Ohta, Tokyo, Japan
² Neurobiology Laboratory, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

Abstract

We compared the developmental changes of 5-hydroxytryptamine (5-HT) 1 A and 5-HT2 A receptor immunoreactivity in the nuclei in relation to the cardiorespiratory or autonomic function in the human brain stem in sudden infant death syndrome (SIDS) and congenital central hypoventilation syndrome (CCHS) patients and age-matched controls by means of immunohistochemical methods. There were significant decreases in 5-HT1 A and 5-HT2 A receptor immunoreactivity in the dorsal nucleus of the vagus, solitary nucleus and ventrolateral medulla in the medulla oblongata, and significant increases in the periaqueductal gray matter (PAG) of the midbrain in SIDS victims, but there were no significant differences between those in CCHS patients and controls. The decreased immunoreactivity of the receptors in the medulla oblongata was accompanied by brain stem gliosis. Therefore, the decreases in the receptors may be secondary to chronic hypoxia or repeated ischemia, but may be causally related to some impairment of the developing cardiorespiratory neuronal system. As 5-HT1 A and 5-HT2 A receptors were the most abundant in the fetal period and then decreased with subsequent development, the increases in 5-HT1 A and 5-HT2 A receptor immunoreactivity in PAG may reflect delayed neuronal maturation, but may also reflect compensatory changes in response to hypofunctioning serotonergic neurons in the medulla oblongata in SIDS. There was no abnormal expression of 5-HT1 A and 5-HT2 A receptors in CCHS brain stems, and so the pathophysiology seems to be different between SIDS and CCHS patients.

Key words

Sudden Infant Death Syndrome - Congenital Central Hypoventilation Syndrome - Serotonergic Receptor - Brain stem

Full Text

References

1 Amiel J, Salomon R, Attie T, Pelet A, Trang H, Mokhtari M. et al . Mutations of the RET-GDNF signaling pathway in Ondine's curse. Am J Hum Genet. 1998; 62 715-717
2 Armstrong D, Sachis P, Bryan C, Becker L. Pathological features of persistent infantile sleep apnea with reference to the pathology of sudden infant death syndrome. Ann Neurol. 1982; 12 169-174
3 Becker L E. Neural maturational delay as a link in the chain of events leading to SIDS. Can J Neurol Sci. 1990; 17 361-371
4 Becker L E, Takashima S. Chronic hypoventilation and development of brain stem gliosis. Neuropediatrics. 1985; 16 19-23
5 Beitz A J. Central gray. Paxinos G The Human Central Nervous System. San Diego; Academic Press Inc 1990: 307-320
6 Bergstrom L, Lagercrantz H, Terenius L. Post-mortem analysis of neuropeptides in brains from sudden infant death victims. Brain Res. 1984; 323 279-285
7 Commare M C, Franois B, Estournet B, Barois A. Ondine's curse: a discussion of five cases. Neuropediatrics. 1993; 24 313-318
8 DeArmond S J, Fusco M M, Dewey M M. Structure of the Human Brain. A Photographic Atlas. Vol. 3. Coronal Sections of the Gross Brain and Brain stem. 3rd ed. New York; Oxford University Press 1989: 36-61
9 Denoroy L, Gay N, Gilly R, Tayot J, Pasquier B, Kopp N. Catecholamine synthesizing enzyme activity in brainstem areas from victims of sudden infant death syndrome. Neuropediatrics. 1987; 18 187-190
10 Di Pasquale E, Morin D, Monteau R, Hilaire G. Serotonergic modulation of the respiratory rhythm generator at birth: an in vitro study in the rat. Neurosci Lett. 1992; 143 91-95
11 Filiano J J, Kinney H C. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate. 1994; 65 194-197
12 Folgering H, Kuyper F, Kille J F. Primary alveolar hypoventilation (Ondine's curse syndrome) in an infant without an external arcuate nucleus. Case report. Bull Europ Physiopath Resp. 1979; 15 659-665
13 Guilleminault C, Ariagno R, Korobkin R, Nagel L, Baldwin R, Coons S. et al . Mixed and obstructive sleep apnea and near miss for sudden infant death syndrome. 2. Comparison of near miss and normal control infant by age. Pediatrics. 1979; 64 882-891
14 Haddad G G, Mazza N M, Defendini R, Blanc W A, Driscoll J M, Epstein M AF. et al . Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate. Medicine. 1978; 57 517-526
15 Hamada S, Senzaki K, Hamaguchi-Hamada K, Tabuchi K, Yamamoto H, Yamamoto T. et al . Localization of 5-HT2A receptor in rat cerebral cortex and olfactory system revealed by immunohistochemistry using two antibodies raised in rabbit and chicken. Mol Brain Res. 1998; 54 199-211
16 Harper R M, Ni H, Zhang J. Discharge relationships of periaqueductal gray neurons to cardiac and respiratory patterning during sleep and waking states. Depaulis A, Bandler R The Midbrain Periaqueductal Gray Matter. New York; Plenum Press 1991: 41-55
17 Harper R M, Leake B, Hoffman H, Walter D O, Hoppenbrouwers T, Hodgman J. et al . Periodicity of sleep states is altered in infants at risk for the sudden infant death syndrome. Science. 1981; 213 1030-1033
18 Hilaire G, Monteau R, Gauthier P, Rega P, Morin D. Functional significance of the dorsal and ventral respiratory group in adult and newborn rats: in vivo and in vitro studies. Neurosci Lett. 1990; 111 133-138
19 Hoyer D, Clarke D E, Fozard J R, Hartig P R, Martin G R, Mylecharane E J. et al . International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev. 1994; 46 157-203
20 Hunt C E. Impaired arousal from sleep: relationship to sudden infant death syndrome. J Perinatol. 1989; 9 184-187
21 Jiang M, Chandler S D, Ennis M, Shipley M T, Behbehani M M. Actions of epinephrine on neurons in the rat midbrain periaqueductal gray matter maintained in vitro. Brain Res Bull. 1992; 29 871-877
22 Kinney H C, Burger P C, Harrell F E, Hudson R P. “Reactive gliosis” in the medulla oblongata of victims of the sudden infant death syndrome. Pediatrics. 1983; 72 181-187
23 Kinney H C, Brody B A, Finkelstein S P, Vawter G F, Mandell F, Gilles F H. Delayed central nervous system myelination in the sudden infant death syndrome. J Neuropathol Exp Neurol. 1991; 50 29-48
24 Kinney H C, Filiano J J, Harper R M. The neuropathology of the sudden infant death syndrome. A review. J Neuropathol Exp Neurol. 1992; 51 115-126
25 Kopp N, Chigr F, Denoroy L, Gilly R, Jordan D. Absence of adrenergic neurons in nucleus tractus solitarius in sudden infant death syndrome. Neuropediatrics. 1993; 24 25-29
26 Kopp N, Denoroy L, Eymin C, Gay N, Richard F, Awano K. et al . Studies of neuroregulators in the brain stem of SIDS. Biol Neonate. 1994; 65 189-193
27 Lalley P M, Bischoff A-M, Richter D W. 5-HT1 A receptor-mediated modulation of medullary expiratory neurons in the cat. J Physiol. 1994; 476 117-130
28 Lalley P M, Bischoff A-M, Schwarzacher S W, Richter D W. 5-HT2 receptor-controlled modulation of medullary respiratory neurons. J Physiol. 1995; 487 653-661
29 Liu H M, Loew J M, Hunt C E. Congenital central hypoventilation syndrome . a pathologic study of the neuromuscular system. Neurology. 1978; 28 1013-1019
30 Martin G R, Humphery P PA. Receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature. Neuropharmacology. 1994; 33 261-273
31 McCall R B, Clement M E. Roles of serotonin 1 A and serotonin 2 receptors in the central regulation of the cardiovascular system. Pharmacol Rev. 1994; 46 231-243
32 Morilak D A, Ciaranello R D. Ontogeny of 5-hydroxytryptamine 2 receptor immunoreactivity in the developing rat brain. Neurosci. 1993; 55 869-880
33 Nieuwenhuys R, Voogd J, van Huijzen J. The Human Central Nervous System. A Synopsis and Atlas. Part IV: Microscopical Sections. Transverse Sections Through the Brain Stem and Spinal Cord. 3rd ed. Berlin; Springer-Verlag 1988: 104-141
34 Obonai T, Yasuhara M, Nakamua T, Takashima S. Catecholamine neurons alteration in the brain stem of sudden infant death syndrome victims. Pediatrics. 1998; 101 283-288
35 Obonai T, Takashima S, Becker L E, Asanuma M, Mizuta R, Horie H. et al . Relationship of substance P and gliosis in medulla oblongata in neonatal sudden infant death syndrome. Pediatr Neurol. 1996; 15 189-192
36 Panigrahy A, Filiano J, Sleeper L A, Mandell F, Valdes-Dapena M, Krous H F. 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
37 Poceta J S, Strandjord T P, Badura R J, Milstein J M. Ondine's curse and neurocristopathy. Pediatr Neurol. 1987; 3 370-372
38 Quattrochi J J, McBride P T, Yates A J. Brainstem immaturity in sudden infant death syndrome: a quantitative rapid Golgi study of dendritic spines in 95 infants. Brain Res. 1985; 325 39-48
39 Saito Y, Itoh M, Ozawa Y, Obonai T, Kobayashi Y, Washizawa K. et al . Changes of neurotransmitters in the brainstem of patients with respiratory-pattern disorders during childhood. Neuropediatrics. 1999; 30 133-140
40 Takashima S, Armstrong D, Becker L E, Huber J. Cerebral white matter lesions in the sudden infant death syndrome. Pediatrics. 1978; 62 155-159
41 Takashima S, Armstrong D, Becker L E, Bryan C. Cerebral hypoperfusion in the sudden infant death syndrome? Brain stem gliosis and vasculature. Ann Neurol. 1978; 4 257-262
42 Takashima S, Becker L E. Prenatal and postnatal maturation of medullary “respiratory centers”. Dev Brain Res. 1986; 26 173-177
43 Takashima S, Becker L E. Developmental abnormalities of medullary respiratory centers in sudden infant death syndrome. Exp Neurol. 1985; 90 580-587
44 Weese-Mayer D E, Silvestri J M, Menzies L J, Morrow-Kenny A S, Hunt C E, Hauptman S A. Congenital central hypoventilation syndrome: diagnosis, management, and long-term outcome in thirty-two children. J Pediatr. 1992; 120 381-387
45 Willinger M, James L S, Catz C. Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatr Pathol. 1991; 11 677-684
46 Yamanouchi H, Takashima S, Becker L E. Correlation of astrogliosis and substance P immunoreactivity in the brainstem of victims of sudden infant death syndrome. Neuropediatrics. 1993; 24 200-203
47 Zec N, Filano J J, Panigraphy A, White W F, Kinney H C. Developmental changes in [³H]lyserigic acid diethylamine ([³H]LSD) binding to serotonin receptors in the human brainstem. J Neuropathol Exp Neurol. 1996; 55 114-126

M. D. Yuri Ozawa

Department of Neonatology
Toho University School of Medicine

6 - 11 - 1, Ohmorinishi, Ohta

Tokyo 143 - 8541

Japan

Email: hy_ozawa@d6.dion.ne.jp