An In Vivo 1H Magnetic Resonance Spectroscopy Study of the Deep Cerebellar Nuclei in Children with Fetal Alcohol Spectrum Disorders
Article first published online: 21 MAR 2014
Copyright © 2014 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 38, Issue 5, pages 1330–1338, May 2014
How to Cite
du Plessis, L., Jacobson, J. L., Jacobson, S. W., Hess, A. T., van der Kouwe, A., Avison, M. J., Molteno, C. D., Stanton, M. E., Stanley, J. A., Peterson, B. S. and Meintjes, E. M. (2014), An In Vivo 1H Magnetic Resonance Spectroscopy Study of the Deep Cerebellar Nuclei in Children with Fetal Alcohol Spectrum Disorders. Alcoholism: Clinical and Experimental Research, 38: 1330–1338. doi: 10.1111/acer.12380
- Issue published online: 22 APR 2014
- Article first published online: 21 MAR 2014
- Manuscript Accepted: 10 JAN 2014
- Manuscript Received: 20 MAY 2013
- National Institute on Alcohol Abuse and Alcoholism. Grant Numbers: R01 AA016781, R01 AA09524, U01 AA014790, R21AA017410, U24 AA014815, FA2005040800024
- President of Wayne State University
- NIAAA Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)
- NIH Office of Research on Minority Health
- South African Research Chairs Initiative of the Department of Science and Technology
- National Research Foundation of South Africa
- Focus Area Grant. Grant Number: FA2005040800024
- South African National Research Foundation
- University of Cape Town
- Fetal Alcohol Spectrum Disorders;
- Prenatal Alcohol Exposure;
- Magnetic Resonance Spectroscopy;
Prenatal alcohol exposure has been linked to impairment in cerebellar structure and function, including eyeblink conditioning. The deep cerebellar nuclei, which play a critical role in cerebellar-mediated learning, receive extensive inputs from brain stem and cerebellar cortex and provide the point of origin for most of the output fibers to other regions of the brain. We used in vivo 1H magnetic resonance spectroscopy (MRS) to examine effects of prenatal alcohol exposure on neurochemistry in this important cerebellar region.
MRS data from the deep cerebellar nuclei were acquired from 37 children with heavy prenatal alcohol exposure and 17 non- or minimally exposed controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa.
Increased maternal alcohol consumption around time of conception was associated with lower N-Acetylaspartate (NAA) levels in the deep nuclei (r = −0.33, p < 0.05). Higher levels of alcohol consumption during pregnancy were related to lower levels of the choline-containing metabolites (r = −0.37, p < 0.01), glycerophosphocholine plus phosphocholine (Cho). Alcohol consumption levels both at conception (r = 0.35, p < 0.01) and during pregnancy (r = 0.38, p < 0.01) were related to higher levels of glutamate plus glutamine (Glx). All these effects continued to be significant after controlling for potential confounders.
The lower NAA levels seen in relation to prenatal alcohol exposure may reflect impaired neuronal integrity in the deep cerebellar nuclei. Our finding of lower Cho points to disrupted Cho metabolism of membrane phospholipids, reflecting altered neuropil development with potentially reduced content of dendrites and synapses. The alcohol-related alterations in Glx may suggest a disruption of the glutamate–glutamine cycling involved in glutamatergic excitatory neurotransmission.