Brain concentrations of glutamate and GABA in human epilepsy: A review

Sarlo, Gabrielle L.; Holton, Kathleen F.

doi:10.1016/j.seizure.2021.06.028

Cited by 73 publications

(45 citation statements)

References 58 publications

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“…Epilepsy represents a group of neurological disorders characterized by recurrent seizures that can vary from brief absence episodes to continuous tonic–clonic motor activity. The seizures are a product of abnormal electrical activity of the brain, frequently caused by either excessive excitatory activity (glutamate) or reduced inhibitory control (GABA) [ 85 ]. Continued seizure activity may develop into SE, which is associated with both morbidity and mortality.…”

Section: Resultsmentioning

confidence: 99%

Laminin as a Biomarker of Blood–Brain Barrier Disruption under Neuroinflammation: A Systematic Review

Zapata-Acevedo

García-Pérez

Cabezas-Pérez

et al. 2022

IJMS

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Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood–brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (β and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.

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Section: Resultsmentioning

confidence: 99%

Laminin as a Biomarker of Blood–Brain Barrier Disruption under Neuroinflammation: A Systematic Review

Zapata-Acevedo

García-Pérez

Cabezas-Pérez

et al. 2022

IJMS

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“…Synaptically released glutamate plays a major role in the initiation and spread of epileptic activity [57,58]. The modulation of glutamatergic signaling by mGluR agonists is a possible treatment strategy [59].…”

Section: Naag In Epilepsymentioning

confidence: 99%

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Morland

Nordengen

2022

IJMS

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N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG—for instance by inhibiting GCPII—is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels.

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“…Microtubule binding and GABA receptor binding are two Gene Ontology (GO) annotations for this gene. GABA and glutamate are the two major neurotransmitters that influence seizures, and the balance of the two neurotransmitters in the nervous system is particularly important for the prevention of epileptogenesis [ 48 ]. In another study on GRE, the authors found a disturbance in the glutamatergic neurotransmitter pathway [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy

Wang

Xie

et al. 2022

BMC Genomics

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Background Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive. Objective To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. Methods Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. Results We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease’s progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance. Conclusion These findings can offer a fresh perspective on GRE-induced brain network changes.

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Brain concentrations of glutamate and GABA in human epilepsy: A review

Cited by 73 publications

References 58 publications

Laminin as a Biomarker of Blood–Brain Barrier Disruption under Neuroinflammation: A Systematic Review

Laminin as a Biomarker of Blood–Brain Barrier Disruption under Neuroinflammation: A Systematic Review

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy

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