The cause of the sudden infant death syndrome (SIDS), which claims 8000 lives each year, is known. A widely-held hypothesis is that SIDS is due to an abnormality in brainstem sites involved in cardiorespiratory regulation during sleep and occurs during a critical period in their maturation and integration. Since a qualitative brainstem abnormality is not seen by conventional histopathologic criteria, we are testing the hypothesis that there is a quantitative brainstem pathology in SIDS. We are quantitating selected cellular and chemical parameters of brainstem maturation and injury with 3-dimensional (3-D), computer-based methods of developed in the Department of Neuroscience, Children's Hospital, Boston. We are examining several parameters relative to one another, as no one single parameter carries enough information.
Our specific aims are to test critically whether there is in SIDS victims: 1) a quantitative increase in the density of reactive astrocytes (""""""""scar cells"""""""") in brainstem nuclei related to cardiorespiratory and/or sleep-waking regulation; 2) a deviation in number, density and/or size of neuronal subclasses in the same nuclei; 3) axonal degeneration in relevant brainstem pathways; and/or 4) a quantitative deviation in the developmental profile a postsynaptic receptors of selected neurotransmitter (NT) systems involved in cardiorespiratory and sleep- waking regulation. We also intend: 5) to correlate brainstem findings with systemic abnormalities, e.g., hepatic erythropoiesis, determined by collaborators in the same study population. Two further aims that are fundamental to SIDS data collection are: 6) establish a computerized, 3-D data-base describing the cyto- and chemoarchitectonic organization of the human fetal and infant brainstem; and 7) develop efficient strategies for 3-D sampling in structurally and neurochemically heterogeneous brainstem nuclei. Our pilot cytological data suggest that there is almost a 50% difference in opiate receptor binding in the nucleus of the tractus solitarius, the major integrative site of cardiorespiratory reflexes. These potentially important leads warrant intense pursuit, as undisputable evidence for a brainstem abnormality could provide a critical step towards discovering the cause of SIDS.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020991-05
Application #
3319559
Study Section
Special Emphasis Panel (SSS (10))
Project Start
1985-12-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Haynes, Robin L; Frelinger 3rd, Andrew L; Giles, Emma K et al. (2017) High serum serotonin in sudden infant death syndrome. Proc Natl Acad Sci U S A 114:7695-7700
Paterson, David S (2013) Serotonin gene variants are unlikely to play a significant role in the pathogenesis of the sudden infant death syndrome. Respir Physiol Neurobiol 189:301-14
Haynes, Robin L; van Leyen, Klaus (2013) 12/15-lipoxygenase expression is increased in oligodendrocytes and microglia of periventricular leukomalacia. Dev Neurosci 35:140-54
Cummings, Kevin J; Commons, Kathryn G; Trachtenberg, Felicia L et al. (2013) Caffeine improves the ability of serotonin-deficient (Pet-1-/-) mice to survive episodic asphyxia. Pediatr Res 73:38-45
Serang, Oliver; Froehlich, John W; Muntel, Jan et al. (2013) SweetSEQer, simple de novo filtering and annotation of glycoconjugate mass spectra. Mol Cell Proteomics 12:1735-40
McDowell, Gary S; Gaun, Aleksandr; Steen, Hanno (2013) iFASP: combining isobaric mass tagging with filter-aided sample preparation. J Proteome Res 12:3809-12
Edlow, Brian L; Haynes, Robin L; Takahashi, Emi et al. (2013) Disconnection of the ascending arousal system in traumatic coma. J Neuropathol Exp Neurol 72:505-23
Randall, Bradley B; Paterson, David S; Haas, Elisabeth A et al. (2013) Potential asphyxia and brainstem abnormalities in sudden and unexpected death in infants. Pediatrics 132:e1616-25
Kinney, Hannah C; McDonald, Anna G; Minter, Megan E et al. (2013) Witnessed sleep-related seizure and sudden unexpected death in infancy: a case report. Forensic Sci Med Pathol 9:418-21
Broadbelt, Kevin G; Rivera, Keith D; Paterson, David S et al. (2012) Brainstem deficiency of the 14-3-3 regulator of serotonin synthesis: a proteomics analysis in the sudden infant death syndrome. Mol Cell Proteomics 11:M111.009530

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