Thyrotropin Receptor Signaling Deficiency Impairs Spatial Learning and Memory

Subclinical hyperthyroidism, a disease characterized by decreased thyroid-stimulating hormone (TSH) and normal concentration of thyroid hormone, is associated with an elevated risk for cognitive impairment. TSH is the major endogenous ligand of TSH receptor (TSHR) and its role dependent on the process of signal transduction of TSHR. It has not, however, been established whether TSHR signaling are involved in the regulation of cognition. In the current study, Tshr deletion leads to significantly compromised performance in hippocampus-dependent tasks, along with reduced dendritic spine density and excitatory synaptic density as well as altered synaptic structure in CA1 subfield of the hippocampus. Furthermore, the synapse-related gene expression was altered in the hippocampus of Tshr-/- mice. These findings suggest the ablation of TSHR signaling impairs spatial learning and memory, which reveals a fresh role of TSHR signaling in brain. Hippocampal mRNA profiles of 3-month old wild type (WT) and Tshr-/- mice were generated by deep sequencing from five biological replicates, using Illumina Novaseq6000