Glial Dysfunction in Abstinent Methamphetamine Abusers
Open Access
- 30 December 2009
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 30 (5), 950-960
- https://doi.org/10.1038/jcbfm.2009.261
Abstract
Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized 13C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects ( P>0.1). However, glial 13C-bicarbonate production rate from [1-13C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 μmol/g per min ( N=5) versus controls 0.11 μmol/g per min ( N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous 13C MRS methods may determine ‘cause and effect’ between glial failure and neuronal injury.Keywords
This publication has 45 references indexed in Scilit:
- Glutamate transmission in addictionNeuropharmacology, 2009
- Ornithine Transcarbamylase Deficiency with Persistent Abnormality in Cerebral Glutamate Metabolism in AdultsRadiology, 2009
- Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobeJournal of Magnetic Resonance, 2008
- MR Spectroscopy in Diagnosis and Neurological Decision-MakingSeminars in Neurology, 2008
- Glutamatergic substrates of drug addiction and alcoholismBiochemical Pharmacology, 2007
- Frontal Glucose Hypometabolism in Abstinent Methamphetamine UsersNeuropsychopharmacology, 2005
- Reduced glutamate neurotransmission in patients with Alzheimer's disease?an in vivo 13C magnetic resonance spectroscopy studyMagnetic Resonance Materials in Physics, Biology and Medicine, 2003
- Tricarboxylic acid cycle of glia in the in vivo human brainNMR in Biomedicine, 2002
- Measurement of the Tricarboxylic Acid Cycle Rate in Human Grey and White Matter in Vivo by 1H-[13C] Magnetic Resonance Spectroscopy at 4.1TJournal of Cerebral Blood Flow & Metabolism, 1999
- Acetate and fluoroacetate as possible markers for glial metabolism in vivoBrain Research, 1986