Effects of long-term infliximab and tocilizumab treatment on anxiety-like behavior and cognitive function in naive rats
| Autor: | Chryssa Pourzitaki, Dimitrios Kouvelas, Athanasios Saitis, Spyridon Panagiotopoulos, Maria Eleni Manthou, Foteini Malliou, Ioannis Tsimoulas, Frideriki Poutoglidou |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Hippocampus Hippocampal formation Anxiety Antibodies Monoclonal Humanized Amygdala chemistry.chemical_compound Tocilizumab Cognition Neurotrophic factors Internal medicine medicine Animals Prefrontal cortex Pharmacology Behavior Animal business.industry Interleukin-6 Tumor Necrosis Factor-alpha Brain-Derived Neurotrophic Factor Brain General Medicine Infliximab Rats medicine.anatomical_structure Endocrinology Treatment Outcome chemistry Gene Expression Regulation medicine.symptom business medicine.drug |
| Zdroj: | Pharmacological reports : PR. 74(1) |
| ISSN: | 2299-5684 |
| Popis: | Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain. |
| Databáze: | OpenAIRE |
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