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

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Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice
Psychopharmacology ( IF 3.5 ) Pub Date : 2023-11-15 , DOI: 10.1007/s00213-023-06489-2
Piotr Wlaź ₁ , Adrian Wiater ₂ , Małgorzata Majewska ₂ , Elżbieta Wyska ₃ , Marcin Grąz ₄ , Joanna Śliwa-Dominiak ₅ , Nikola Gapińska ₁ , Katarzyna Socała ₁

Affiliation

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 ivPTZ- and electrically-induced seizure tests. The effect on the antiseizure potency of valproate was assessed in the scPTZ 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 ivPTZ test. L. helveticus R0052 did not affect the threshold for tonic seizures both in the maximal electroshock- and ivPTZ-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.

中文翻译：

膳食补充瑞士乳杆菌 R0052 对小鼠癫痫发作阈值和丙戊酸钠抗癫痫效力的影响

目的

动物和人类研究虽然有限，但都表明，多菌株益生菌补充剂可能会减少癫痫发作的数量和/或癫痫发作的严重程度。在这里，我们评估了单一菌株益生菌补充剂对小鼠癫痫发作易感性、丙戊酸钠的抗癫痫功效和几个行为参数的影响。

方法

瑞士乳杆菌R0052 口服 28 天。在 ivPTZ 和电诱导的癫痫发作试验中评估了它对癫痫发作阈值的影响。在 scPTZ 测试中评估了丙戊酸酯抗癫痫效力的影响。我们还研究了益生菌补充剂对焦虑相关行为（在高架加迷宫和光明/黑暗箱测试中）、运动协调性（在加速旋转测试中）、神经肌肉力量（在握力测试中）和自发运动活动的影响。HPLC 法测定血清和脑丙戊酸盐浓度以及盲肠 SCFA 和乳酸含量。

结果

L. helveticus 瑞士乳杆菌R0052 显着增加了 6 Hz 诱导的精神运动性癫痫发作的阈值。在 ivPTZ 测试中，肌阵挛性和阵挛性癫痫发作的阈值也略有增加。L.helveticus R0052 在最大电击和 IVPTZ 诱导的癫痫发作试验中均不影响强直性癫痫发作的阈值。未报道丙戊酸钠对 PTZ 诱导的癫痫发作的抗癫痫效力发生变化。有趣的是，瑞士乳杆菌 R0052 增加了血清中的丙戊酸盐浓度，但增加了大脑中的丙戊酸盐浓度。此外，L.helveticus R0052 对焦虑相关行为、运动协调、神经肌肉力量和运动活动没有产生任何显着影响。补充瑞士乳杆菌 R0052 导致总 SCFAs、乙酸盐和丁酸盐的浓度增加。