{"title":"Preventive and therapeutic impact of probiotic supplementation on behavior and inflammatory responses in the PTZ-induced chemical kindling in rats.","authors":"Saeed Tahmasebi, Samad Farashi Bonab, Soudeh Ghafouri-Fard, Solat Eslami","doi":"10.1007/s00213-025-06760-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy is a common neurological disorder that affects the quality of life globally. Its pathophysiology involves disruptions in ion transport, excitatory-inhibitory imbalances, and regulatory systems. It has been shown that there is a crosstalk between the brain and the gut, where the brain influences the digestive system and the gut can affect brain functions and behavior. This study postulates that probiotic supplementation has both preventive and therapeutic impacts on epilepsy through modulation of inflammatory responses and improvement of brain function.</p><p><strong>Materials and methods: </strong>Male rats were gavaged with three probiotic strains (Lactobacillus reuteri, Bifidobacterium longum, Bifidobacterium lactis) daily for 28 days (10^9 CFU/mL) before inducing epilepsy with pentylenetetrazol (PTZ) injections (37.5 mg/kg every 48 h for 14 injections). Probiotic supplements were continued during disease induction. The effects of probiotics on seizure behavior, histopathology, and pro-inflammatory gene expression were assessed.</p><p><strong>Results: </strong>Probiotic consumption significantly reduced seizure severity, with evident effects from the fourth injection onwards (days 8-28). It delayed the onset of stage 2 and 5 seizures during kindling but had no major effect on stage 5 stability time. Histopathological analysis revealed amelioration of neuronal injury. Besides, there was a significant decrease in the expression of pro-inflammatory genes (Il-1β, Il-6, Ifng) and an increase in the expression of the anti-inflammatory Il-10 in the probiotic-treated model group.</p><p><strong>Conclusion: </strong>Probiotics may have both preventive and therapeutic effects on PTZ-induced seizures through reduction of severity of seizures and modulating inflammatory responses. Additional studies are necessary to clarify the mechanisms, as treatment was given before and during kindling.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06760-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Preventive and therapeutic impact of probiotic supplementation on behavior and inflammatory responses in the PTZ-induced chemical kindling in rats.
Introduction: Epilepsy is a common neurological disorder that affects the quality of life globally. Its pathophysiology involves disruptions in ion transport, excitatory-inhibitory imbalances, and regulatory systems. It has been shown that there is a crosstalk between the brain and the gut, where the brain influences the digestive system and the gut can affect brain functions and behavior. This study postulates that probiotic supplementation has both preventive and therapeutic impacts on epilepsy through modulation of inflammatory responses and improvement of brain function.
Materials and methods: Male rats were gavaged with three probiotic strains (Lactobacillus reuteri, Bifidobacterium longum, Bifidobacterium lactis) daily for 28 days (10^9 CFU/mL) before inducing epilepsy with pentylenetetrazol (PTZ) injections (37.5 mg/kg every 48 h for 14 injections). Probiotic supplements were continued during disease induction. The effects of probiotics on seizure behavior, histopathology, and pro-inflammatory gene expression were assessed.
Results: Probiotic consumption significantly reduced seizure severity, with evident effects from the fourth injection onwards (days 8-28). It delayed the onset of stage 2 and 5 seizures during kindling but had no major effect on stage 5 stability time. Histopathological analysis revealed amelioration of neuronal injury. Besides, there was a significant decrease in the expression of pro-inflammatory genes (Il-1β, Il-6, Ifng) and an increase in the expression of the anti-inflammatory Il-10 in the probiotic-treated model group.
Conclusion: Probiotics may have both preventive and therapeutic effects on PTZ-induced seizures through reduction of severity of seizures and modulating inflammatory responses. Additional studies are necessary to clarify the mechanisms, as treatment was given before and during kindling.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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