Article Figures & Data
Figures
- Fig 1.
Glutamatergic synapse: Glutamate determines neurotransmission by acting on postsynaptic receptors. EAATs, localized on the astrocytic membrane, rapidly terminate glutamatergic activity. EAAT activity is tightly coupled to glucose consumption, causing transient increase in lactate levels. Increased lactate may be an important immediate source of energy to firing neurons. Note the tight neuronal-astrocytic interaction, which is fundamental for the glutamate/glutamine coupling and the compartmentalization of glutamate. Glutamine synthesis in astrocytes is an important mechanism of ammonia detoxification. Note:—Pyr indicates pyruvate; Lac = lactate; GS = glutamine synthetase.
- Fig 2.
GABAergic synapse. GABA is synthesized from glutamate by the action of GAD and is stored in vesicles by a vesicular neurotransmitter transporter. Once released in the synapse, GABA acts on its receptors (GABA Rc) and shapes the inhibitory action potential. GABA activity is terminated by its uptake through GABA transporters by surrounding neurons and astrocytes. GABA is metabolized through transamination into succinic semialdehyde catalyzed by GABA-transaminase (GABA shunt). Note:—GABA Rc = GABA receptors.
- Fig 3.
NAAG neurotransmission and neuromodulation. NAAG is synthesized in neurons via NAAG synthase. NAAG is co-released with glutamate from actively firing neurons. Intrasynaptic NAAG binds as a weak antagonist on NMDAR and also to mGlu3 receptors inhibiting further release of glutamate (inhibitory feedback loop). NAAG is hydrolyzed to NAA and Glu by GCPII enzyme on astrocytes.
Tables
Selected studies reporting 1H-MR spectroscopy-detected glutamate and GABA changes in the in vivo brains of patients with neurologic disorders
Neurologic Disorders Technique Region of Interest MRSI Findings Reference Epilepsy MTS Short TE PRESS (Glx); DQF (GABA) Hippocampus No change in Glx/Cr and GABA/Cr before and after surgical resection Simister et al, 200936 MTS (MRI negative) Short TE PRESS Hippocampus Non-significant increase in Glx/Cr Woermann et al, 199935 Idiopathic generalized epilepsy Short TE PRESS (Glx); DQF (GABA) Frontal cortex Increased Glx/NAA and Glx/ins in patients, no changes in GABA Simister et al, 200359 Tuberous sclerosis complex MEGAPRESS Cortical tubers Increased GABA in tubers, no change in Glx Taki et al, 200960 anti-GAD positive epilepsy MEGAPRESS Primary sensorimotor cortex Decreased GABA/NAA, no changes in Glx/NAA Stagg et al, 201061 Malformations of cortical development Short TE PRESS (Glx); DQF (GABA) Cortical malformations Increased GABA/Cr and Glx/Cr Simister et al, 200762 Juvenile myoclonic epilepsy Short TE PRESS Primary motor cortex/cingulum/ medial prefrontal cortex Reduced Glx/Cr Lin et al, 200963 Drugs and epilepsy Levetiracetam MEGAPRESS Occipital cortex Increased GABA/Cr in responders Doelken, 201064 Vigabatrin Difference editing Occipital cortex Increased GABA/Cr in responders Mueller et al, 200165; Petroff et al, 199934 Topiramate Difference editing Occipital cortex Acute increase in GABA/Cr Petroff et al, 200166 Gabapentin Difference editing Occipital cortex Acute increase in GABA/Cr Petroff et al, 199633 Brain tumors MRSI Low-grade oligodendroglioma vs low-grade astrocytoma Increased Glx in low-grade oligodendrogliomas Rijpkema et al, 200367 ALS TE-averaged PRESS Primary motor cortex and internal capsule Increased Glx/Cr, increased Glu/Cr Han and Ma, 201041 Migraine TE-averaged PRESS ACC and insula Low NAAG/Gln in ACC of patients, high NAAG/Gln in insula of patients Prescot et al, 200968 AD Macromolecule subtraction Hippocampus Decreased Glu/NAA, Glu/Cr; Glu/mI Rupsingh et al, 201145 68-ms TE PRESS Posterior cingulate gyrus Reduced Glx/Cr Antuono et al, 200169 Short TE PRESS Precuneus, posterior cingulate cortex, parieto-occipital white matter Decreased Glx/Cr in gray matter only Hattori et al, 200270 Drugs and AD Galantamine Macromolecule subtraction Hippocampus Increased Glu Penner et al, 201048 Memantine MRSI Bilateral hippocampi Decreased Glu/Cr Glodzik et al, 200871 PD Short TE PRESS Posterior cingulate gyrus Reduced Glu/Cr Griffith et al, 200849 TE averaged PRESS Lentiform nucleus No change in Glu Kickler et al, 200756 STEAM Substantia nigra Increased GABA/Glu Oz et al, 200672 -
Note:—MTS indicates mesial temporal sclerosis; MRI, MR imaging; GAD, glutamic acid decarboxylase; PRESS, point-resolved spectroscopic sequence; Glx, glutamine/glutamate; DQF, double-quantum filter; MEGAPRESS, MEGA point-resolved spectroscopy; MRSI, MR spectroscopy imaging; STEAM, short echo time stimulated echo acquisition mode; ACC, anterior cingulate cortex; ins, inositol; Glu, glutamate; Gln, glutamine
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