Probiotic supplementation alleviates absence seizures and anxiety- and depression-like behavior in WAG/Rij rat by increasing neurotrophic factors and decreasing proinflammatory cytokines

• Published in: Epilepsy & behavior Vol. 128; p. 108588
• Main Authors: Aygun, Hatice, Akin, Ali Tugrul, Kızılaslan, Nildem, Sumbul, Orhan, Karabulut, Derya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2022
• Subjects: Absence epilepsy; Animals; Anxiety; Anxiety-depression; Cytokines; Depression; Dietary Supplements; Disease Models, Animal; Electroencephalography; Epilepsy, Absence; Humans; Male; Nerve Growth Factors; Neuroinflammation; Neurotrophic factor; Probiotics - therapeutic use; Rats; Rats, Wistar; Seizures; SOX2; SOX2; Neurotrophic factor; NO; Anxiety-depression; Neuroinflammation; Absence epilepsy
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2022.108588

•Probiotics may have anti-seizure and antidepressant/anxiolytic effects in WAG/Rij rat.•SOX2, BDNF and NGF could play roles on the absence epilepsy pathophysiology.•Probiotics show anti-inflammatory effect by reducing TNF-α, IL-6, NO levels in WAG/Rij rats.
Epilepsy is one of the most common chronic brain disorders that affect millions of people worldwide. In the present study, we investigated the effects of probiotic supplementation on absence epilepsy and anxiety-and depression-like behavior in WAG/Rij rats.
Fourteen male WAG/Rij rats (absence-epileptic) and seven male Wistar rats (nonepileptic) were used. The effects of probiotic VSL#3 (12.86 bn living bacteria/kg/day for 30 day/gavage) on absence seizures, and related psychiatric comorbidities were evaluated in WAG/Rij rats. Anxiety-like behavior was evaluated by the open-field test and depression-like behavior by the forced swimming test. In addition, the brain tissues of rats were evaluated histopathologically for nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], SRY sex-determining region Y-box 2 [SOX2] and biochemically for nitric oxide [NO], tumor necrosis factor-alpha [TNF-α] ,and Interleukin-6 [IL-6].
Compared to Wistar rats, WAG/Rij rats exhibited anxiety- and depression-like behavior, and had lower BDNF, NGF and SOX2 immunoreactivity, and higher TNF-α, IL-6 levels in brain tissue. VSL#3 supplementation reduced the duration and number of spike-wave discharges (SWDs) and exhibited anxiolytic or anti-depressive effect. VSL#3 supplement also increased the NGF immunoreactivity while decreasing IL-6, TNF-α and NO levels in WAG/Rij rat brain.
The findings of the present study showed that neurotrophins, SOX2 deficiency, and pro-inflammatory cytokines may play a role in the pathogenesis of absence epilepsy. Our data support the hypothesis that the probiotics have anti-inflammatory effect. The present study is the first to show the positive effects of probiotic bacteria on absence seizures and anxiety- and depression-like behavior.