Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a 1H-magnetic resonance spectroscopy study
- 277 Downloads
In utero exposure to alcohol leads to a spectrum of fetal alcohol related disorders (FASD). However, few studies used have used proton magnetic resonance spectroscopy (1H-MRS) to understand how neurochemical disturbances relate to the pathophysiology of FASD. Further, no studies to date have assessed brain metabolites in infants exposed to alcohol in utero. We hypothesize that neonates exposed to alcohol in utero will show decreased glutamatergic activity, pre-emptive of their clinical diagnosis or behavioural phenotype. Single voxel 1H-MRS data, sampled in parietal white and gray matter, were acquired from 36 neonates exposed to alcohol in utero, and 31 control unexposed healthy neonates, in their 2nd-4th week of life. Metabolites relative to creatine with phosophocreatine and metabolites absolute concentrations using a water reference are reported. Male infants exposed to alcohol in utero were found to have reduced concentration of glutamate with glutamine (Glx) in their parietal white matter (PWM), compared to healthy male infants (p = 0.02). Further, male infants exposed to alcohol in utero had reduced concentration and ratio for glutamate (Glu) in their PWM (p = 0.02), compared to healthy male infants and female infants exposed to alcohol in utero. Female infants showed higher relative Glx and Glu ratios for parietal gray matter (PGM, p < 0.01), compared to male infants. We speculate that the decreased Glx and Glu concentrations in PWM are a result of delayed oligodendrocyte maturation, which may be a result of dysfunctional thyroid hormone activity in males exposed to alcohol in utero. Further study is required to elucidate the relationship between Glx and Glu, thyroid hormone activity, and oligodendrocyte maturation in infants exposure to alcohol in utero.
KeywordsMRS Alcohol exposure Gray matter Oligodendrocytes Thyroid hormone
Proton magnetic resonance spectroscopy
fetal alcohol spectrum disorders
glutamate with glutamine concentration
parietal white matter
parietal gray matter
We thank two MRI experts who assisted during the development of the MRI protocol – Dr André van der Kouwe, MGH Harvard University, USA, and Dr Stefan Blüml, University of Southern California, USA. Mrs Robyn Kalan, our study’s neonatal nurse, who cared for the infants during scan preparation and during the MRI scan. We thank the study staff and the staff at Paarl Hospital, Mbekweni and TC Newman clinics for their support of the study. We also wish to thank the Drakenstein child lung and health research team and staff, led by PI Dr Heather Zar, who without, this study would not have been possible. Lastly, we thank the families and infants who participated in this study.
Compliance with ethical standards
The study was supported by a Foundation of Alcohol Research grant as well as the Bill and Melinda Gates Foundation [OPP 1017641]. FMH also acknowledges her funding source, administered by the Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, a Hasso Plattner mid-career development programme award.
- Dell Statistica (2015) Dell Statistica data analysis software system, version 13. Dell Inc.Google Scholar
- Goodlett CR, Horn KH, Zhou FC (2005) Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exp Biol Med (Maywood) 230(6):394–406Google Scholar
- Lebel C, Mattson SN, Riley EP, et al. (2012) A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development. J Neurosci 32(44):15243–15251. doi: 10.1523/JNEUROSCI.1161-12.2012 CrossRefPubMedPubMedCentralGoogle Scholar
- Leigland LA, Budde MD, Cornea A, et al. (2013a) Diffusion MRI of the developing cerebral cortical gray matter can be used to detect abnormalities in tissue microstructure associated with fetal ethanol exposure. NeuroImage 83:1081–1087. doi: 10.1016/j.neuroimage.2013.07.068 CrossRefPubMedGoogle Scholar
- WMA General Assembly (2000) World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000Google Scholar
- Wozniak JR, Muetzel RL, Mueller BA, et al. (2009) Microstructural corpus callosum anomalies in children with prenatal alcohol exposure: an extension of previous diffusion tensor imaging findings. Alcohol Clin Exp Res 33(10):1825–1835. doi: 10.1111/j.1530-0277.2009.01021.x CrossRefPubMedPubMedCentralGoogle Scholar