Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice

• Published in: Psychopharmacology Vol. 241; no. 2; pp. 327 - 340
• Main Authors: Wlaź, Piotr, Wiater, Adrian, Majewska, Małgorzata, Wyska, Elżbieta, Grąz, Marcin, Śliwa-Dominiak, Joanna, Gapińska, Nikola, Socała, Katarzyna
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2024; Springer Nature B.V
• Subjects: Acetic acid; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Anxiety; Bioavailability; Biomedical and Life Sciences; Biomedicine; Brain; Cecum; Dietary Supplements; Electroconvulsive therapy; Electroshock; Humans; Lactobacillus helveticus; Locomotor activity; Mice; Motor ability; Neurosciences; Original Investigation; Pharmacology/Toxicology; Probiotics; Psychiatry; Seizures; Seizures - drug therapy; Sodium valproate; Valproic acid; Valproic Acid - pharmacology; Valproic Acid - therapeutic use; Psychobiotic; Gut-microbiota-brain axis; Anticonvulsant; Excitation/inhibition balance; Microbiota-derived metabolites
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-023-06489-2

Objective Both animal and human studies, though limited, showed that multi-strain probiotic supplementation may reduce the number of seizures and/or seizure severity. Here, we evaluated the effect of a single strain probiotic supplementation on seizure susceptibility, antiseizure efficacy of sodium valproate, and several behavioral parameters in mice. Methods Lactobacillus helveticus R0052 was given orally for 28 days. Its influence on seizure thresholds was evaluated in the iv PTZ- and electrically-induced seizure tests. The effect on the antiseizure potency of valproate was assessed in the sc PTZ test. We also investigated the effects of probiotic supplementation on anxiety-related behavior (in the elevated plus maze and light/dark box tests), motor coordination (in the accelerating rotarod test), neuromuscular strength (in the grip-strength test), and spontaneous locomotor activity. Serum and brain concentrations of valproate as well as cecal contents of SCFAs and lactate were determined using HPLC method. Results L. helveticus  R0052 significantly increased the threshold for the 6 Hz-induced psychomotor seizure. There was also a slight increase in the threshold for myoclonic and clonic seizure in the iv PTZ test. L.   helveticus  R0052 did not affect the threshold for tonic seizures both in the maximal electroshock- and iv PTZ-induced seizure tests. No changes in the antiseizure potency of valproate against the PTZ-induced seizures were reported. Interestingly, L.   helveticus  R0052 increased valproate concentration in serum, but not in the brain. Moreover, L.   helveticus  R0052 did not produce any significant effects on anxiety-related behavior, motor coordination, neuromuscular strength, and locomotor activity. L.   helveticus  R0052 supplementation resulted in increased concentrations of total SCFAs, acetate, and butyrate. Conclusions Altogether, this study shows that a single-strain probiotic – L.   helveticus  R0052 may decrease seizure susceptibility and this effect can be mediated, at least in part, by increased production of SCFAs. In addition, L.   helveticus  R0052 may affect bioavailability of valproate, which warrants further investigations.