ArticleMolecular neurobiology2021
Hypothyroidism Induces Interleukin-1-Dependent Autophagy Mechanism as a Key Mediator of Hippocampal Neuronal Apoptosis and Cognitive Decline in Postnatal Rats.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- A study of the correlation between cognitive function and thyroid hormones in patients with Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Biochemical, Immunohistochemical and Behavioral Effects of Spexin in a Methimazole-Induced Hypothyroidism Rat Model.Biology · 2026Article
- Neurological consequences of adult-onset hypothyroidism.Endocrine journal · 2025Review
- The impact of autoimmune thyroid disease on cognitive and psychiatric disorders: focus on clinical, pre-clinical and molecular studies.European thyroid journal · 2025Review
- Mucin 5AC Promotes Breast Cancer Brain Metastasis through cMET/CD44v6.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Exploring the potential anti-senescence effects of soybean-derived peptide Soymetide in mice hippocampal neurons via the Wnt/β-catenin pathway.Frontiers in pharmacology · 2025Article
- Increased thyroid stimulating hormone (TSH) as a possible risk factor for atherosclerosis in subclinical hypothyroidism.Thyroid research · 2024Review
- miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway.Molecular medicine reports · 2024Article
- Thyroid dysfunction and Alzheimer's disease, a vicious circle.Frontiers in endocrinology · 2024Review
- Primary Hypothyroidism and Alzheimer's Disease: A Tale of Two.Cellular and molecular neurobiology · 2023Review
- The effect of hyperthyroidism on cognitive function, neuroinflammation, and necroptosis in APP/PS1 mice.Journal of translational medicine · 2023Article
- A Fine Regulation of the Hippocampal Thyroid Signalling Protects Hypothyroid Mice against Glial Cell Activation.International journal of molecular sciences · 2022Article
- Arsenic Induces Differential Neurotoxicity in Male, Female, and E2-Deficient Females: Comparative Effects on Hippocampal Neurons and Cognition in Adult Rats.Molecular neurobiology · 2022Article
- Review
- Thyroid hormone: sex-dependent role in nervous system regulation and disease.Biology of sex differences · 2021Review
- Gallic Acid Prevents the Oxidative and Endoplasmic Reticulum Stresses in the Hippocampus of Adult-Onset Hypothyroid Rats.Frontiers in pharmacology · 2021Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thyroid hormone (TH) is essential for brain development, and hypothyroidism induces cognitive deficits in children and young adults. However, the participating mechanisms remain less explored. Here, we examined the molecular mechanism, hypothesizing the involvement of a deregulated autophagy and apoptosis pathway in hippocampal neurons that regulate cognitive functions. Therefore, we used a rat model of developmental hypothyroidism, generated through methimazole treatment from gestation until young adulthood. We detected that methimazole stimulated the autophagy mechanism, characterized by increased LC3B-II, Beclin-1, ATG7, and ATG5-12 conjugate and decreased p-mTOR/mTOR and p-ULK1/ULK1 autophagy regulators in the hippocampus of developing and young adult rats. This methimazole-induced hippocampal autophagy could be inhibited by thyroxine treatment. Subsequently, probing the upstream mediators of autophagy revealed an increased hippocampal neuroinflammation, marked by upregulated interleukin (IL)-1alpha and beta and activated microglial marker, Iba1, promoting neuronal IL-1 receptor-1 expression. Hence, IL-1R-antagonist (IL-1Ra), which reduced hippocampal neuronal IL-1R1, also inhibited the enhanced autophagy in hypothyroid rats. We then linked these events with hypothyroidism-induced apoptosis and loss of hippocampal neurons, where we observed that like thyroxine, IL-1Ra and autophagy inhibitor, 3-methyladenine, reduced the cleaved caspase-3 and TUNEL-stained apoptotic neurons and enhanced Nissl-stained neuronal count in methimazole-treated rats. We further related these molecular results with cognition through Y-maze and passive avoidance tests, demonstrating an IL-1Ra and 3-methyladenine-mediated improvement in learning-memory performances of the hypothyroid rats. Taken together, our study enlightens the critical role of neuroinflammation-dependent autophagy mechanism in TH-regulated hippocampal functions, disrupted in developmental hypothyroidism.
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