Aberrant Development of Hippocampal GABAergic Neurons Arising from Hypothyroidism Contributes to Memory Deficits in Mice Through Maf Suppressing Mef2c
Year: 2025
Type: article
Abstract: Background/Objectives: Thyroid hormone (TH) deficiency during the pregnancy and lactation periods leads to enduring memory impairments in offspring. However, the mechanisms underlying the cognitive and memory deficits induced by developmental hypothyroidism remain largely unexplored. Methods: Mice were exposed to propylthiouracil (PTU) or purified water to detect changes in hippocampal neurogenesis and differentiation of their offspring to explain the pathogenesis of impaired learning and memory. In addition, HT22 cell line were used to investigate the regulation between Maf and Mef2c. Results: Our findings indicate that developmental exposure to PTU results in abnormalities of the preferential differentiation of GABAergic interneurons and a subsequent reduction in PV+ inhibitory interneurons in the hippocampus of mouse pups. More significantly, we also indicate that the downregulation of Maf and the consequent alteration of Mef2c are likely responsible for the mechanisms through which developmental hypothyroidism influences the differentiation and development of PV+ inhibitory interneurons in offspring. Conclusions: Consequently, the aberrant development of PV+ interneuron in the hippocampus of mice subjected to developmental hypothyroidism potentially contributes to memory deficits during adolescence and adulthood.
Source: Biomedicines
Authors: Mengyan Wu, Xingdong Zeng, Yongle Cai, Haonan Chen, Hao Yang
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,137
Awards: G4556923752, G6294663458
OpenAlex ID: W4411210129
