The sudden infant death syndrome (SIDS) is the sudden death of an infant that remains unexplained after a complete review of the history, autopsy, and death scene investigation;it is the leading cause of postneonatal infant mortality in the United States today. Based upon our findings to date, we hypothesize that SIDS is due to an underlying abnormality in the medullary homeostatic network that: 1) results in a failure of protective responses to life-threatening stressors during sleep in a critical developmental period; and 2) importantly involves serotonin (5-hydroxytryptamine, 5-HT), y-aminobutyric acid (GABA), and their potential interactions with other neurotransmitter systems and the signal transduction family 14-3-3. Initiated in 1998, our program brings together a highly committed group of 23 investigators and their trainees to address the potential role of the brain in SIDS. Located at 3 medical institutions across the country and the medical examiner's system in San Diego, CA, we bring to bear upon the SIDS problem outstanding expertise in multiple clinical and scientific disciplines in 3 integrated projects and 2 cores (Administrativ and Neuroanatomy). The 7 inter-related themes proposed for investigation with state-of-the-art methodologies in the next (fourth) cycle are: 1) gene expression profiles of the medullary homeostatic network in SIDS infants and animal models (Projects I and II;2) the interaction of prenatal exposures (hypoxia and nicotine) with preexisting 5-HT dysfunction that potentially leads to homeostatic impairment in the postnatal period (Projects II and III);3) the mechanism(s) of physiological derangements in protective homeostatic responses related to 5-HT and GABA, including autoresuscitation, arousal, and the laryngeal chemoreflex (Projects II and III);4) the development and connectivity of subtypes of brainstem 5-HT neurons related to different homeostatic functions (Projects III);5) a potential link between abnormalities in the caudal/rostral 5-HT domains of the brainstem and hippocampal targets in SIDS brains (Project I);6) treatment of abnormalities in animal models with specific drugs (Project II);and 7) the development of future biomarkers of brainstem pathology in SIDS infants.
The determination of the cause(s) and mechanism(s) of SIDS, as sought in this program, is the essential step towards developing specific biomarkers and therapies for infants at risk to prevent all SIDS deaths. A critical strength of the program is its demonstrated capacity to integrate human and animal studies that inform and expand upon each other. In essence, there is no other scientific group in the United States that is investigating the neural basis of SIDS in such a cohesive, synergistic, stable, and productive way.
|Dosumu-Johnson, Ryan T; Cocoran, Andrea E; Chang, YoonJeung et al. (2018) Acute perturbation of Pet1-neuron activity in neonatal mice impairs cardiorespiratory homeostatic recovery. Elife 7:|
|Babb, Jessica A; Linnros, Sofia E; Commons, Kathryn G (2018) Evidence for intact 5-HT1A receptor-mediated feedback inhibition following sustained antidepressant treatment in a rat model of depression. Neuropharmacology 141:139-147|
|Darnall, Robert A; Chen, Xi; Nemani, Krishnamurthy V et al. (2017) Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism. Pediatr Res 82:164-172|
|Tenpenny, Richard C; Commons, Kathryn G (2017) What Gene Mutations Affect Serotonin in Mice? ACS Chem Neurosci 8:987-995|
|Cerpa, Veronica J; Wu, Yuanming; Bravo, Eduardo et al. (2017) Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development. Neuroscience 344:1-14|
|Ehlinger, Daniel G; Commons, Kathryn G (2017) Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities. Eur J Neurosci 46:2416-2425|
|Panzini, Chris M; Ehlinger, Daniel G; Alchahin, Adele M et al. (2017) 16p11.2 deletion syndrome mice perseverate with active coping response to acute stress - rescue by blocking 5-HT2A receptors. J Neurochem 143:708-721|
|Commons, Kathryn G; Cholanians, Aram B; Babb, Jessica A et al. (2017) The Rodent Forced Swim Test Measures Stress-Coping Strategy, Not Depression-like Behavior. ACS Chem Neurosci 8:955-960|
|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|
|Guo, Yue-Ping; Commons, Kathryn G (2017) Serotonin neuron abnormalities in the BTBR mouse model of autism. Autism Res 10:66-77|
Showing the most recent 10 out of 143 publications