Our laboratory has provided evidence that a large proportion of infants dying of Sudden Infant Death Syndrome (SIDS) have abnormalities of the medullary serotonergic (5-HT) system, which is responsible for modulation of multiple homeostatic functions. A risk factor for SIDS is maternal alcohol consumption during the first trimester. We hypothesize that in utero exposure to alcohol during early gestation affects the development and function of the medullary 5-HT system. A mouse model of maternal alcohol consumption will be used to address the hypotheses that prenatal alcohol exposure affects the: (1) cellular and neurochemical development and functions of 5-HT neurons; (2) the development of 5-HT neurons through the suppression of 5-HT-specific transcription factor Pet-1 and the signaling molecules responsible for 5-HT precursor development; and (3) the chemoreception function of 5-HT neurons in response to hypercarbia and hypoxia. The overall goal of this project is to understand the basis of fetal alcohol exposure as a risk factor for SIDS, and to ultimately develop therapeutic strategies to alleviate the adverse effects associated with fetal alcohol exposure. The project will be done at Children's Hospital Boston with access to all resources from Children's, as well as surrounding hospitals in the Harvard community, including excellent laboratory facilities, seminar series, and continuing education. The project proposed will be done in close association with a program project on SIDS involving Harvard, Dartmouth, and Yale. This infrastructure will allow invaluable collaborations with experts who are co-sponsors of this project. Nearly all aspects of this project are new to the candidate, providing the opportunity to learn multiple new areas of science. Through the course of this work, the candidate will progress to independence, and prepare for writing an RO1. The RO1 will stem from work proposed in this grant, and thus, this work will be a critical step towards the establishment of a laboratory with the candidate as Principal Investigator.
| Haynes, Robin L; Xu, Gang; Folkerth, Rebecca D et al. (2011) Potential neuronal repair in cerebral white matter injury in the human neonate. Pediatr Res 69:62-7 |
