title: An in vivo 1H magnetic resonance spectroscopy study of the deep cerebellar nuclei in children with fetal alcohol spectrum disorders.
abstract: BACKGROUND
  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 (1) H magnetic resonance spectroscopy (MRS) to examine effects of prenatal alcohol exposure on neurochemistry in this important cerebellar region.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa; Department of Human Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Lindie
authors.initials: L
authors.lastname: du Plessis
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Jacobson
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Jacobson
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Hess
authors.forename: Andre
authors.initials: A
authors.lastname: van der Kouwe
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Avison
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Molteno
authors.forename: Mark E
authors.initials: ME
authors.lastname: Stanton
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
authors.forename: Ernesta M
authors.initials: EM
authors.lastname: Meintjes
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D002529:Cerebellar Nuclei / Q000737:chemistry / Q000473:pathology*; D002648:Child; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005997:Glycerylphosphorylcholine / Q000032:analysis; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D059906:Neuroimaging; D010767:Phosphorylcholine / Q000032:analysis
chemical_list: D010767:Phosphorylcholine; D001224:Aspartic Acid; D005997:Glycerylphosphorylcholine; C000179:N-acetylaspartate
keywords: Choline; Fetal Alcohol Spectrum Disorders; Glutamate; Magnetic Resonance Spectroscopy; N-Acetylaspartate; Prenatal Alcohol Exposure