Reduced GABA levels in the medial prefrontal cortex are associated with cognitive impairment in patients with NMOSD

Yang, Yang; Rui, Qianyun; Han, Shuting; Wu, Xiaojuan; Wang, Xiaoyuan; Wu, Peng; Shen, Yueping; Dai, Hui; Xue, Qun; Li, Yonggang

doi:10.1016/j.msard.2022.103496

Cited by 15 publications

(11 citation statements)

References 51 publications

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“…Especially in the hippocampus and in the sensorimotor cortex GABA-levels were significantly reduced in patients with MS. Furthermore, their motor and sensory performance were impaired in comparison with healthy subjects, as it was also confirmed in further independent studies ( Cawley et al, 2015 ; Cao et al, 2018 ; Yang et al, 2022 ). Therefore, GABA-levels can be used as a specific biomarker for neurodegeneration, among other established techniques like proton magnetic resonance spectroscopy ( Bai et al, 2015 ; De Stefano and Giorgio, 2015 ; Riese et al, 2015 ; Nantes et al, 2017 ; Gao et al, 2018 ).…”

Section: The Influence Of the Extracellular Matrix On Parvalbumin-exp...supporting

confidence: 74%

Regulation of the E/I-balance by the neural matrisome

Mueller-Buehl

Wegrzyn

Bauch

et al. 2023

Front. Mol. Neurosci.

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In the mammalian cortex a proper excitatory/inhibitory (E/I) balance is fundamental for cognitive functions. Especially γ-aminobutyric acid (GABA)-releasing interneurons regulate the activity of excitatory projection neurons which form the second main class of neurons in the cortex. During development, the maturation of fast-spiking parvalbumin-expressing interneurons goes along with the formation of net-like structures covering their soma and proximal dendrites. These so-called perineuronal nets (PNNs) represent a specialized form of the extracellular matrix (ECM, also designated as matrisome) that stabilize structural synapses but prevent the formation of new connections. Consequently, PNNs are highly involved in the regulation of the synaptic balance. Previous studies revealed that the formation of perineuronal nets is accompanied by an establishment of mature neuronal circuits and by a closure of critical windows of synaptic plasticity. Furthermore, it has been shown that PNNs differentially impinge the integrity of excitatory and inhibitory synapses. In various neurological and neuropsychiatric disorders alterations of PNNs were described and aroused more attention in the last years. The following review gives an update about the role of PNNs for the maturation of parvalbumin-expressing interneurons and summarizes recent findings about the impact of PNNs in different neurological and neuropsychiatric disorders like schizophrenia or epilepsy. A targeted manipulation of PNNs might provide an interesting new possibility to indirectly modulate the synaptic balance and the E/I ratio in pathological conditions.

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Section: The Influence Of the Extracellular Matrix On Parvalbumin-exp...supporting

confidence: 74%

Regulation of the E/I-balance by the neural matrisome

Mueller-Buehl

Wegrzyn

Bauch

et al. 2023

Front. Mol. Neurosci.

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“…38,39 Dysfunctional GABA activity can disrupt the excitatory/inhibitory balance in the cortex, 40 representing a core pathophysiological mechanism underlying cognitive decline. 41,42 GABA receptors are the target of many drugs including benzodiazepines and anesthetics 43 that might be useful in ameliorating ADT-mediated cognitive effects. 44 Our systematic analyses for functional annotation, clustering using Cytoscape enrichment analysis, establishment of interaction networks, network cluster/module analysis, and TF-target gene network analysis revealed molecular biomarkers of ADT-mediated cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

“…GABA receptors are LGICs and upon activation, mediate the influx of K+/Ca2+ channels, chloride ion, and G‐protein linked intracellular processes, inducing hyperpolarization in postsynaptic neurons 38,39 . Dysfunctional GABA activity can disrupt the excitatory/inhibitory balance in the cortex, 40 representing a core pathophysiological mechanism underlying cognitive decline 41,42 . GABA receptors are the target of many drugs including benzodiazepines and anesthetics 43 that might be useful in ameliorating ADT‐mediated cognitive effects 44 …”

Section: Discussionmentioning

confidence: 99%

Ligand‐gated ion channels as potential biomarkers for ADT‐mediated cognitive decline in prostate cancer patients

Verma,

Singh,

Nagampalli

et al. 2024

Molecular Carcinogenesis

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Men with prostate cancer are at increased risk of developing cognitive decline by the use of second‐generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high‐throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements‐cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease‐related gene associations. Validation analysis of genes was performed on brain neuronal and glial cells by quantitative real‐time polymerase chain reaction assay. Our systematic analysis of androgen deprivation‐associated genes involved multiple biological processes, including neuroactive ligand–receptor interaction, axon guidance, cytokine–cytokine receptor interaction, and metabolic and cancer signaling pathways. Genes associated with neuroreceptor ligand interaction, including gamma‐aminobutyric acid (GABA) A and B receptors and nuclear core proteins, were identified as top upstream regulators. Functional enrichment and protein–protein interaction network analysis highlighted the role of ligand‐gated ion channels (LGICs) and their receptors in cognitive dysfunction. Gene–disease association assigned forgetfulness, intellectual disability, visuospatial deficit, bipolar disorder, and other neurocognitive impairment with upregulation of type‐1 angiotensin II receptor, brain‐derived neurotrophic factor, GABA type B receptor subunit 2 (GABBR2), GABRA3, GABRA5, GABRB1, glycine receptor beta, glutamate ionotropic receptor N‐methyl‐D‐aspartate receptor (NMDA) type subunit 1, glutamate ionotropic receptor NMDA type subunit 2D, 5‐hydroxytryptamine receptor 1D, interferon beta 1, and nuclear receptor subfamily 3 group C member 1 as top differentially expressed genes. Validation studies of brain glial cells, neurons, and patients on ADT demonstrated the association of these genes with cognitive decline. Our findings highlight LGICs as potential biomarkers for ADT‐mediated cognitive decline. Further validation of these biomarkers may lead to future practical clinical use.

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“…Gamma-aminobutyric acid (GABA) represents a natural amino acid that widely exists in numerous organisms [ 1 , 2 ]. In mammals, GABA mainly acts as an inhibitory neurotransmitter [ 3 , 4 ], while also being responsible for many other physiological functions. For instance, GABA has therapeutic effects in liver injury [ 5 ], hepatic encephalopathy [ 6 ], and cardiovascular diseases [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Sodium-Ion-Free Fermentative Production of GABA with Levilactobacillus brevis CD0817

Pei

Wei

et al. 2023

Metabolites

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Gamma-aminobutyric acid (GABA) has positive effects on many physiological processes. Lactic acid bacterial production of GABA is a future trend. This study aimed to produce a sodium-ion-free GABA fermentation process for Levilactobacillus brevis CD0817. In this fermentation, both the seed and fermentation media used L-glutamic acid instead of monosodium L-glutamate as the substrate. We optimized the key factors influencing GABA formation, adopting Erlenmeyer flask fermentation. The optimized values of the key factors of glucose, yeast extract, Tween 80, manganese ion, and fermentation temperature were 10 g/L, 35 g/L, 1.5 g/L, 0.2 mM, and 30 °C, respectively. Based on the optimized data, a sodium-ion-free GABA fermentation process was developed using a 10-L fermenter. During the fermentation, L-glutamic acid powder was continuously dissolved to supply substrate and to provide the acidic environment essential for GABA synthesis. The current bioprocess accumulated GABA at up to 331 ± 8.3 g/L after 48 h. The productivity of GABA was 6.9 g/L/h and the molar conversion rate of the substrate was 98.1%. These findings demonstrate that the proposed method is promising in the fermentative preparation of GABA by lactic acid bacteria.

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Reduced GABA levels in the medial prefrontal cortex are associated with cognitive impairment in patients with NMOSD

Cited by 15 publications

References 51 publications

Regulation of the E/I-balance by the neural matrisome

Regulation of the E/I-balance by the neural matrisome

Ligand‐gated ion channels as potential biomarkers for ADT‐mediated cognitive decline in prostate cancer patients

Sodium-Ion-Free Fermentative Production of GABA with Levilactobacillus brevis CD0817

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