• Vandreza Cardoso Bortolotto, Mustafa Munir Mustafa Dahleh, Luiza Souza Marques, Stífani Machado Araujo Borstmann, Cristini Escobar Viana, Franciane Cabral Pinheiro, Franciéle Romero Machado Balok, Luana Barreto Meichtry, Silvana Peterini Boeira, Gustavo Petri Guerra, Cristina Wayne Nogueira, and Marina Prigol.
• Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences - Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules (LaftamBio), Department of Nutrition - Federal University of Pampa, Itaqui, RS, 97650-000, Brazil. Electronic address: vandrezabortolotto.aluno@unipampa.edu.br.
• Neuroscience. 2025 Feb 6; 566: 283828-38.

AbstractHypothyroidism 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.Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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