The overall objective of this study is to develop an optical coherence tomography (OCT) based high- resolution mouse embryonic brain imaging and analysis approach, and to use this method in correlation with molecular analysis to understand the interplay between ethanol (EtOH) and nicotine (NIC) effects on embryonic brain development. Maternal exposures to these substances are linked to fetal growth retardation and neurotoxicity, and these toxins often co-abused during pregnancy. However, studies on the combined fetal effects of NIC and EtOH are very limited and their combined effects on molecular mechanisms of fetal development, particularly the brain, are poorly understood. Therefore, there is a critical need to understand the interplay between the effects of EtOH and NIC via development of high-resolution imaging technique capable of live longitudinal analysis of developing brain. Intriguingly, our recent studies suggested that EtOH and NIC exert mutually antagonistic effects on fetal neuronal stem cells development. In this proposal, we will investigate if these toxins have indeed antagonistic or synergetic effects on embryonic brain development in live mouse embryos with implementation of an innovative higher-resolution embryonic brain imaging and dynamic quantitative analysis approaches, which we develop. We have pioneered OCT-based methodology for live in utero imaging and longitudinal phenotypic analysis of mouse fetuses in utero. Here we propose to further develop both the technology and the methodology for longitudinal brain imaging and analysis. The study is focused on the second trimester- equivalent period of development, when the neuronal stem cells give rise to most of the neurons of the adult brain. The central hypothesis of this proposal is that EtOH and NIC have partially antagonistic effects in fetal brain development. By successful accomplishment of the proposal, we will establish a live mouse embryonic brain imaging approach, will develop a set of protocols and detailed assessments to quantitatively characterize dynamic embryonic brain development with cellular resolution, and will investigate if EtOH and NIC synergize to disrupt the brain development or exhibit partially antagonistic effects. We will also assess the feasibility of using nicotinic receptor antagonists and agonists t prevent the individual and combined effects of EtOH and NIC. Therefore, studying this effect is highly significant from both fundamental biology and teratogenic points of view since it may have particular significant impact for the development of novel and innovative therapies for reversing teratology.

Public Health Relevance

The proposed research is relevant to public health because it provides a new method for understanding the impacts of maternal ethanol and nicotine consumption during pregnancy on mammalian brain and vasculature development. Ethanol and nicotine consumption during pregnancy is a problem for many women. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will reduce the burdens of human disability, in this case due to exposure to toxins during gestation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD086765-05
Application #
9842558
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Krotoski, Danuta
Project Start
2016-01-01
Project End
2020-12-31
Budget Start
2020-01-01
Budget End
2020-12-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Houston
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
036837920
City
Houston
State
TX
Country
United States
Zip Code
77204
Raghunathan, Raksha; Wu, Chen; Singh, Manmohan et al. (2018) Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography. J Biophotonics 11:e201700238
Lopez 3rd, Andrew L; Larina, Irina V (2018) Dynamic Imaging of Mouse Embryos and Cardiodynamics in Static Culture. Methods Mol Biol 1752:41-52
Liu, Chih-Hao; Nevozhay, Dmitry; Schill, Alexander et al. (2018) Nanobomb optical coherence elastography. Opt Lett 43:2006-2009
Kirillin, Mikhail Yu; Larin, Kirill V; Turchin, Ilya V et al. (2018) Special Section Guest Editorial: Topical Problems of Biophotonics: from Optical Bioimaging to Clinical Biophotonics. J Biomed Opt 23:1-2
Zhang, Jitao; Raghunathan, Raksha; Rippy, Justin et al. (2018) Tissue biomechanics during cranial neural tube closure measured by Brillouin microscopy and optical coherence tomography. Birth Defects Res :
Chen Wu; Shihao Ran; Le, Henry et al. (2017) A dual-modality optical coherence tomography and selective plane illumination microscopy system for mouse embryonic imaging. Conf Proc IEEE Eng Med Biol Soc 2017:4038-4040
Wang, Shang; Garcia, Monica D; Lopez 3rd, Andrew L et al. (2017) Dynamic imaging and quantitative analysis of cranial neural tube closure in the mouse embryo using optical coherence tomography. Biomed Opt Express 8:407-419
Mahnke, Amanda H; Miranda, Rajesh C; Homanics, Gregg E (2017) Epigenetic mediators and consequences of excessive alcohol consumption. Alcohol 60:1-6
Raghunathan, Raksha; Zhang, Jitao; Wu, Chen et al. (2017) Evaluating biomechanical properties of murine embryos using Brillouin microscopy and optical coherence tomography. J Biomed Opt 22:1-6
Bake, Shameena; Gardner, Rachel; Tingling, Joseph D et al. (2017) Fetal Alcohol Exposure Alters Blood Flow and Neurological Responses to Transient Cerebral Ischemia in Adult Mice. Alcohol Clin Exp Res 41:117-127

Showing the most recent 10 out of 18 publications