Gamma‐aminobutyric acid levels in cerebrospinal fluid in neuropaediatric disorders

Cortès‐Saladelafont, Elisenda; Molero-Luís, Marta; Cuadras, Daniel; Casado, Mercedes; Armstrong-Morón, Judith; Yubero, Dèlia; Montoya, Julio; Artuch, Rafael; García‐Cazorla, Àngels

doi:10.1111/dmcn.13746

Cited by 9 publications

(8 citation statements)

References 27 publications

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“…1,2,18 GABA levels are well above elevations that may be seen in other neuropediatric disorders. 39 At physiologic levels, GHB acts at high-affinity sites including GHB receptor(s), a 4 b 1 d-GABA-A receptors (largely located at extrasynaptic sites), and other unidentified GHB receptorsonly about 40% of GHB high-affinity sites have been identified. 6 However, at the extreme levels of GHB seen in succinic semialdehyde dehydrogenase deficiency, GHB also activates low-affinity targets, namely, GABA-B receptors 7,40 and a 4 b 2/ 3 d-GABA-A receptors.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Controlled Trial of SGS-742, a γ-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency

et al. 2021

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We examined safety, tolerability, and efficacy of SGS-742, a γ-aminobutyric acid B (GABA-B) receptor antagonist, in patients with succinic semialdehyde dehydrogenase deficiency. This was a single-center randomized, double-blind crossover phase II clinical trial of SGS-742 versus placebo in patients with succinic semialdehyde dehydrogenase deficiency. Procedures included transcranial magnetic stimulation and the Adaptive Behavior Assessment Scale. Nineteen subjects were consented and enrolled; the mean age was 14.0 ± 7.5 years and 11 (58%) were female. We did not find a significant effect of SGS-742 on the Adaptive Behavior Assessment Scale score, motor threshold, and paired-pulse stimulation. The difference in recruitment curve slopes between treatment groups was 0.003 ( P = .09). There was no significant difference in incidence of adverse effects between drug and placebo arms. SGS-742 failed to produce improved cognition and normalization of cortical excitability as measured by the Adaptive Behavior Assessment Scale and transcranial magnetic stimulation. Our data do not support the current use of SGS-742 in succinic semialdehyde dehydrogenase deficiency. Trial registry number NCT02019667. Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency. https://clinicaltrials.gov/ct2/show/NCT02019667

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Section: Discussionmentioning

confidence: 99%

A Randomized Controlled Trial of SGS-742, a γ-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency

et al. 2021

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“…However, normal concentrations of GABA in body fluids are found to be approximately 10 ng/mL in human plasma and 100 ng/mL in cerebrospinal fluid [ 53 , 54 ]. In addition, various studies reported a decrease of the GABA concentration in a variety of psychiatric and neurological disorders [ 55 , 56 , 57 ]. The imbalance between GABA and its glutamate precursor, an excitatory neurotransmitter, seems to be strongly associated to these conditions [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Probiotic Properties and the Capacity to Form Biofilms of Various Lactobacillus Strains

et al. 2020

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Over the last 20 years, Lactobacillus species inhabiting the gastrointestinal tract (GIT) have received much attention, and their health-promoting properties are now well-described. Probiotic effects cannot be generalized, and their uses cover a wide range of applications. It is thus important to proceed to an accurate selection and evaluation of probiotic candidates. We evaluate the probiotic potential of six strains of Lactobacillus in different in vitro models representing critical factors of either survival, efficacy, or both. We characterized the strains for their ability to (i) modulate intestinal permeability using transepithelial electrical resistance (TEER), (ii) form biofilms and resist stressful conditions, and (iii) produce beneficial host and/or bacteria metabolites. Our data reveal the specificity of Lactobacillus strains to modulate intestinal permeability depending on the cell type. The six isolates were able to form spatially organized biofilms, and we provide evidence that the biofilm form is beneficial in a strongly acidic environment. Finally, we demonstrated the ability of the strains to produce γ-aminobutyric acid (GABA) that is involved in the gut-brain axis and beneficial enzymes that promote the bacterial tolerance to bile salts. Overall, our study highlights the specific properties of Lactobacillus strains and their possible applications as biofilms.

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“…The neurotransmitter γ aminobutyric acid (GABA) has been found to maintain intracellular redox homeostasis and protect neurons from oxidative damage [ 28 ]. Moreover, further evidence showed the level of GABA was reduced in neuropsychiatric diseases [ 29 , 30 ]. Interestingly, intestinal microbiota, such as Lactobacillus SPP and Bifidobacterium , can produce GABA mediators [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers

et al. 2023

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Multiple sclerosis (MS), a distinct autoimmune neuroinflammatory disorder, affects millions of people worldwide, including Saudi Arabia. Changes in the gut microbiome are linked to the development of neuroinflammation via mechanisms that are not fully understood. Prebiotics and probiotics in camel milk that has been fermented have a variety of health benefits. In this study, Bacillus amyloliquefaciens-supplemented camel milk (BASY) was used to assess its preventive effect on MS symptoms in a myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL6J mice model. To this end, MOG-induced experimental autoimmune encephalomyelitis (EAE) was established and the level of disease index, pathological scores, and anti-inflammatory markers of BASY-treated mice using macroscopic and microscopic examinations, qPCR and immunoblot were investigated. The results demonstrate that BASY significantly reduced the EAE disease index, increased total microbial load (2.5 fold), and improved the levels of the short-chain fatty acids propionic, butyric and caproic acids in the diseased mice group. Additionally, myeloperoxidase (MPO) proinflammatory cytokines (IL-1β, IL-6, IL-17, TNF-α) and anti-inflammatory cytokines (TGF-β) were regulated by BASY treatment. Significant suppression of MPO and VCAM levels were noticed in the BASY-treated group (from 168 to 111 µM and from 34 to 27 pg/mL, respectively), in comparison to the EAE group. BASY treatment significantly reduced the expression of inflammatory cytokines, inflammatory progression related transcripts, and inflammatory progression protein markers. In conclusion, BASY significantly reduced the symptoms of EAE mice and may be used to develop a probiotic-based diet to promote host gut health. The cumulative findings of this study confirm the significant neuroprotection of BASY in the MOG-induced mice model. They could also suggest a novel approach to the treatment of MS-associated disorders.

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Gamma‐aminobutyric acid levels in cerebrospinal fluid in neuropaediatric disorders

Abstract: Homeostasis of GABA seems more vulnerable than that of monoamines in the developing brain. The highest GABA levels are found in the primary GABA neurotransmitter disorder SSADH deficiency. GABA alterations are not specific for any clinical or neuroimaging presentation.

Cited by 9 publications

References 27 publications

A Randomized Controlled Trial of SGS-742, a γ-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency

A Randomized Controlled Trial of SGS-742, a γ-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency

Evaluation of the Probiotic Properties and the Capacity to Form Biofilms of Various Lactobacillus Strains

Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers

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