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bioRxiv · 10.1101/2022.04.06.487389

Hippocampal hypothyroidism in mice promotes glial cell activation and spatial memory deficits.

Chamas, L.·Seugnet, I.·Poirier, R.·Clerget-Froidevaux, M.-S.·Enderlin, V.
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Abstract

Adult-onset hypothyroidism is associated with learning and cognitive dysfunctions, which may be related to alterations in synaptic plasticity. Local reduced levels of thyroid hormones (THs) may impair glia morphology and activity, and promote the increase of pro-inflammatory cytokine levels mainly in the hippocampus. Given that neuroinflammation induces memory impairments, hypothyroidism-related glia dysfunction may participate in brain disorders. Thus, we investigated the mechanisms linking hypothyroidism, neuroinflammation and spatial memory, from a protective prospective. We induced hypothyroidism in adult C57BL/6J and wild-derived WSB/EiJ male mice by a seven-week propylthiouracil (PTU) treatment. We previously showed that WSB/EiJ mice were resistant to high-fat diet (HFD)-induced obesity, showing no neuroinflammatory response through adaptive abilities, unlike C57BL/6J. As PTU and HFD treatments are known to induce comparable inflammatory responses, we hypothesized WSB/EiJ mice might also be protected against hypothyroidism-induced neuroinflammation. We showed that hypothyroid WSB/EiJ mice depicted no hippocampal neuroinflammatory response and were able to maintain their hippocampal thyroid signalling despite low circulating TH levels. In contrast, C57BL/6J mice exhibited disturbed hippocampal TH signalling, accompanied by neuroinflammation and memory impairment. Our results reinforce the preponderance of local TH levels over circulating levels and the major role of hippocampal glia reactivity in the establishment of memory deficits.

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Chamas, L., Seugnet, I., Poirier, R., Clerget-Froidevaux, M.-S., Enderlin, V.. 2022-04-10. Hippocampal hypothyroidism in mice promotes glial cell activation and spatial memory deficits.. https://doi.org/10.1101/2022.04.06.487389

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