1. Chrysin modulates the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway: Acting in the improvement of cognitive flexibility and declarative, working and aversive memory deficits caused by hypothyroidism in C57BL/6 female mice.
- Author
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Bortolotto VC, Dahleh MMM, Marques LS, Borstmann SMA, Viana CE, Pinheiro FC, Balok FRM, Meichtry LB, Boeira SP, Guerra GP, Nogueira CW, and Prigol M
- Subjects
- Animals, Female, Mice, Receptor, trkB metabolism, Cognition drug effects, Hippocampus drug effects, Hippocampus metabolism, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Maze Learning drug effects, Maze Learning physiology, Brain-Derived Neurotrophic Factor metabolism, Hypothyroidism drug therapy, Hypothyroidism complications, Hypothyroidism metabolism, Neuronal Plasticity drug effects, Neuronal Plasticity physiology, Mice, Inbred C57BL, Memory Disorders drug therapy, Memory Disorders etiology, Signal Transduction drug effects, Signal Transduction physiology, Proto-Oncogene Proteins c-akt metabolism, Flavonoids pharmacology, Cyclic AMP Response Element-Binding Protein metabolism
- Abstract
Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex. To induce hypothyroidism, mice were exposed to 0.1 % methimazole (MTZ) in the drinking water for 31 days. After confirming low thyroid hormones levels, the mice received either vehicle or chrysin (20 mg/kg) intragastrically once a day for 28 consecutive days. Memory tests were conducted in two separate experiments (experiment 1: Y-maze and reverse Morris water maze; experiment 2: object recognition task and step-down latency), ensuring no memories overlap. Following the tests, the brain samples were collected to analyses ex vivo. Hypothyroid mice exhibited deficits in cognitive flexibility and various memory types, along with altered protein expression related to the BDNF/TrkB/Creb signaling pathway and increased AKT levels in hippocampus and prefrontal cortex. Chrysin treatment effectively reversed these memory deficits, restored cognitive flexibility, and improved protein levels. Our findings suggest that hypothyroidism impairs cognitive flexibility and memory through the BDNF/TrkB/AKT/Creb pathway, which chrysin modulates, operating as a neuroprotector in hypothyroidism. This research sheds light on the potential therapeutic benefits of chrysin for memory-related issues in hypothyroidism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)
- Published
- 2025
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