Chrysin restores memory deficit in hypothyroidism mice: Behavioral, neurochemical and computational approaches involving the neurotrophinergic system
| Autor: | Franciane Cabral Pinheiro, Lucielli Savegnago, Silvana Peterini Boeira, Vandreza Cardoso Bortolotto, Stífani Machado Araujo, Márcia Rósula Poetini, Luana Barreto Meichtry, Mariana G. Fronza, Marina Prigol |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Morris water navigation task Hippocampus Tropomyosin receptor kinase B Mice chemistry.chemical_compound Neurochemical Hypothyroidism Internal medicine Neuroplasticity Animals Medicine Chrysin Maze Learning Prefrontal cortex Biological Psychiatry Flavonoids Memory Disorders biology business.industry Molecular Docking Simulation Psychiatry and Mental health Endocrinology nervous system chemistry biology.protein Female business Neurotrophin |
| Zdroj: | Journal of Psychiatric Research. 144:225-233 |
| ISSN: | 0022-3956 |
| DOI: | 10.1016/j.jpsychires.2021.10.018 |
| Popis: | Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed: open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system. |
| Databáze: | OpenAIRE |
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