Effects of a Gut Microbiome Toxin, p-Cresol, on the Susceptibility to Seizures in Rats

Tevzadze, Gigi; Nanobashvili, Zaqaria; Zhuravliova, Elene; Bilanishvili, I; Shanshiashvili, Lali; Kikvidze, Zaal; Mikeladze, David

doi:10.1007/s11062-019-09774-z

Cited by 7 publications

(4 citation statements)

References 16 publications

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“…This toxin can cross the blood-brain barrier and, by altering dopamine metabolism, changes dopamine receptor activity in different brain areas [8] , [9] . Recently, we have reported that p-cresol can induce differential expression of GluN2B and GluN2A subunits of the N-methyl-d-aspartate receptor (NMDAR) in the hippocampus and nucleus accumbens of healthy and audiogenic seizure-prone rats [10] , [11] . Given that increased p-cresol levels alter brain dopamine metabolism and exacerbate neurological disorders in experimental animals [6] , we propose that the differences in the clinical manifestations in patients with certain neurological disorders may be attributed to the intensity of Clostridium bacterial colonization of the intestinal tract, and correspondingly to the amount of p-cresol in the brain.…”

Section: Introductionmentioning

confidence: 99%

Gut neurotoxin p-cresol induces brain-derived neurotrophic factor secretion and increases the expression of neurofilament subunits in PC-12 cells

Tevzadze

Barbakadze

Kvergelidze

et al. 2021

AIMSN

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<abstract> <p>Increased p-cresol levels reportedly alter brain dopamine metabolism and exacerbate neurological disorders in experimental animals. In contrast to toxic concentrations, low doses of p-cresol may have distinct effects on neuronal metabolism. However, the role of p-cresol in synapse remodeling, neurite outgrowth, and other anabolic processes in neurons remains elusive. We propose that low doses of p-cresol affect neuronal cell structural remodeling compared with the high concentration-mediated harmful effects. Thus, the effects of p-cresol on the secretion of brain-derived neurotrophic factor (BDNF) and neurofilament subunit expression were examined using rat pheochromocytoma cells (PC-12 cells). We observed that low doses of p-cresol potentiated nerve growth factor-induced differentiation via secretion of BDNF in cultured PC-12 cells. Opioidergic compounds modulated these p-cresol effects, which were reversed by oxytocin. We propose that this effect of p-cresol has an adaptive and compensatory character and can be attributed to the induction of oxidative stress. Accordingly, we hypothesize that low doses of p-cresol induce mild oxidative stress, stimulating BDNF release by activating redox-sensitive genes. Given that the intestinal microbiome is the primary source of endogenous p-cresol, the balance between gut microbiome strains (especially Clostridium species) and opioidergic compounds may directly influence neuroplasticity.</p> </abstract>

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Section: Introductionmentioning

confidence: 99%

Gut neurotoxin p-cresol induces brain-derived neurotrophic factor secretion and increases the expression of neurofilament subunits in PC-12 cells

Tevzadze

Barbakadze

Kvergelidze

et al. 2021

AIMSN

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“…P-cresol treatment initiated after a 3-day acclimatization period. The amount of p-cresol and timing is defined according to previous experiments (Tevzadze, 2018 1 ) to avoid depression-like behavior induced through the administration of high doses of p-cresol.…”

Section: Methodsmentioning

confidence: 99%

“…P-cresol, a byproduct of bacterial fermentation in mammalian intestines, has been implicated in various mental disorders. Several studies on children’s groups in different countries show a positive, high-confidence correlation between mental disorders, such as autism and epilepsy, with elevated amounts of p-cresol in the urine (Altieri, 2011; Gabriele, 2014; Tevzadze, 2017); Moreover, several animal experiments show, that elevated amount of p-cresol can induce depression-like disorders, and heightened epilepsy reactions (Tevzadze, 2018; Tevzadze, 2018 1 ). In recent years, more and more studies have linked gut microbiota with different mental incapabilities, such as Alzheimer’s and Parkinson’s diseases (Bostanciklioglu, 2018; Zhu, 2022).…”

Section: Introductionmentioning

confidence: 99%

Bettering of Learning Activity through Elevated P-Cresol Levels in the Brain: Insights from Active Avoidance Testing in Wistar Rats

Tevzadze,

Kikvidze

2024

Preprint

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It is established that p-cresol, a compound produced by bacterial colonies within the gastrointestinal tract of mammals, plays a contributory role in the manifestation of various mental disorders. Recently, our research demonstrated that diminishing p-cresol levels in the brain adversely impact the behavioral manifestation of cognitive abilities in rats. In this study, we aimed to investigate the impact of augmenting p-cresol levels in the brain on learning. The Active Avoidance Test was employed to assess learning capabilities. The results, with a high level of confidence, indicated that rats with an increased concentration of p-cresol in the brain exhibited superior task performance and accelerated learning compared to the control group.

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“…There is more or less agreement on the existence of gut-brain axis in the scientific community: when a substance produced by bacteria in the gut can cross the blood-brain barrier and induce NMDAglutamate receptor modulation 5 , which in turn trigger the activation of dopaminergic systems. There are experimental data when application of gut-derived substance produced in animals causes behaviors similar to both epilepsy and autism 6 .…”

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confidence: 99%

Untitled

2021

J Ment Health Clin Psychol

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Effects of a Gut Microbiome Toxin, p-Cresol, on the Susceptibility to Seizures in Rats

Cited by 7 publications

References 16 publications

Gut neurotoxin p-cresol induces brain-derived neurotrophic factor secretion and increases the expression of neurofilament subunits in PC-12 cells

Gut neurotoxin p-cresol induces brain-derived neurotrophic factor secretion and increases the expression of neurofilament subunits in PC-12 cells

Bettering of Learning Activity through Elevated P-Cresol Levels in the Brain: Insights from Active Avoidance Testing in Wistar Rats

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