Synaptic loss in a mouse model of euthyroid Hashimoto's thyroiditis: possible involvement of the microglia

• Published in: BMC neuroscience Vol. 23; no. 1; p. 25
• Main Authors: Wang, Fen, Cai, Yao-Jun, Ma, Xiao, Wang, Nan, Wu, Zhang-Bi, Sun, Yan, Xu, Yong-Xia, Yang, Hao, Liu, Tian-Tian, Xia, Qin, Yu, Zhen, Zhu, De-Fa
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.04.2022; BioMed Central; BMC
• Subjects: Alzheimer's disease; Animal cognition; Animals; Care and treatment; Cognitive ability; Diagnosis; Disease Models, Animal; Disease susceptibility; Females; Hashimoto Disease; Hashimoto’s thyroiditis; Health aspects; Homeostasis; Immunoassay; Laboratory animals; Memory; Methods; Mice; Mice, Inbred NOD; Microglia; Microglia - pathology; Microscopy; Morphology; Neurophysiology; Phagocytosis; Postsynaptic density proteins; Risk factors; Rodent model; Spatial discrimination learning; Spatial memory; Synapses; Synaptic density; Synaptic loss; Synaptophysin; Testing; Thyroglobulin; Thyroid gland; Thyroiditis; Thyroiditis, Autoimmune; Tumor necrosis factor-TNF; Ultrastructure; China; Hashimoto’s thyroiditis; Synaptic loss; Phagocytosis; Rodent model; Microglia
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-022-00710-2

Hashimoto's thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.