Book Review: GABA and Glutamate in the Human Brain

Petroff, Ognen A. C.

doi:10.1177/1073858402238515

Cited by 545 publications

(455 citation statements)

References 87 publications

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“…However, what may be the function of increasing glutamate and glutamine? Glutamine is the metabolic precursor of glutamate in the mammalian brain (Petroff, 2002). After synaptic transmission of glutamate, surrounding glia cells metabolize glutamate to glutamine, which is in turn transported to the neurons were it is synthesized to glutamate (Petroff, 2002).…”

Section: Discussionmentioning

confidence: 99%

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

Thielen

Hong

Rankouhi

et al. 2018

Human Brain Mapping

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The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long‐term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ‐aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face–name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory‐related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory‐related functional connectivity in a medial prefrontal–thalamus–hippocampus network.

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Section: Discussionmentioning

confidence: 99%

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

Thielen

Hong

Rankouhi

et al. 2018

Human Brain Mapping

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“…25,26 Putrescine can be converted to GABA through an acetylated intermediate while glutamate is capable of modification to ornithine, the precursor of putrescine. 27 Changes in levels of polyamines induced by misexpression of their biosynthetic and catabolic enzymes may therefore confer a reduced neuroprotective capacity to states of oxygen deprivation or metabolic stress in these regions.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

et al. 2007

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The prefrontal cortex is believed to play a major role in depression and suicidal behavior through regulation of cognition, memory, recognition of emotion, and anxiety-like states, with numerous post-mortem studies documenting a prefrontal serotonergic dysregulation considered to be characteristic of depressive psychopathology. This study was carried out to detect changes in gene expression associated with both suicide and major depression using oligonucleotide microarrays (Affymetrix HG-U133 chip set) summarizing expression patterns in primarily ventral regions of the prefrontal cortex (BA44, 45, 46 and 47). A total of 37 male subjects were included in this study, of which 24 were suicides (depressed suicides = 16, nondepressed suicides = 8) and 13 were matched controls. All subjects were clinically characterized by means of psychological autopsies using structured interviews. Unique patterns of differential expression were validated in each of the cortical regions evaluated, with group-specific changes highlighting the involvement of several key neurobiological pathways that have been implicated in both suicide and depression. An overrepresentation of factors involved in cell cycle control and cell division (BA44), transcription (BA44 and 47) and myelination (BA46) was seen in gene ontology analysis of differentially expressed genes, which also highlights changes in the expression of genes involved in ATP biosynthesis and utilization across all areas. Gene misexpression in BA46 was most pronounced between the two suicide groups, with many significant genes involved in GABAergic neurotransmission. The pronounced misexpression of genes central to GABAergic signaling and astrocyte/ oligodendrocyte function provides further support for a central glial pathology in depression and suicidal behavior.

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“…95 Inhibitory neurotransmission in the mammalian brain is mainly accomplished by gabaergic neurons, responsible for the release of GABA. 96 GABA neurotransmission modulates the activity of noradrenergic, dopaminergic and serotonergic systems. 96 Clinical data have pointed to an alteration in gabaergic neurotransmission in mood disorders and more specifically in major depression.…”

Section: Discussionmentioning

confidence: 99%

“…96 GABA neurotransmission modulates the activity of noradrenergic, dopaminergic and serotonergic systems. 96 Clinical data have pointed to an alteration in gabaergic neurotransmission in mood disorders and more specifically in major depression. 97 Thus, cerebrospinal fluid and plasma studies have observed altered levels of GABA in depressed patients.…”

Section: Discussionmentioning

confidence: 99%

Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

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Book Review: GABA and Glutamate in the Human Brain

Cited by 545 publications

References 87 publications

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

Patterns of gene expression in the limbic system of suicides with and without major depression

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