-Original-

Association of Subclinical Thyroid Dysfunction with Cognitive Impairment in Rats: The Role of Autophagy

Yun-Tian Yang^1,2,#, Shan Jin^1,3,#, Yin-Bao Bai⁴, Yousheng Liu⁵ and Eef Hogervorst¹

¹School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, United Kingdom
²Departments of Neurology, Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Autonomous Region, China
³Department of General Surgery, Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Autonomous Region, China
⁴Departments of Thyroid Surgery, People's Hospital of Inner Mongolia Autonomous Region, Inner Mongolia Autonomous Region, China
⁵Department of General Surgery, Datong Third People's Hospital, Shanxi Province, China
^#Contributed equally

Background: We investigated the effect of subclinical hyperthyroidism and subclinical hypothyroidism on cognitive function in rats and the role of autophagy in this process.
Methods: Forty Wistar rats were randomized into normal control (NC), hyperthyroidism (Hyper), hypothyroidism (Hypo), subclinical hyperthyroidism (sHyper), and subclinical hypothyroidism (sHypo) groups. Cognitive function (spatial learning and memory) was tested by the Morris water maze test. Hippocampal histopathology was analyzed by H&E staining, and expression levels of caspase-3 in hippocampal CA1 neurons were measured. In addition, immunoblot analysis was performed to detect hippocampal autophagy-related proteins.
Results: Escape latency from day 1 to day 4 was significantly longer in the Hypo, Hyper, and sHyper groups than in the NC group (P < 0.01). In addition, the number of rats crossing the virtual platform was significantly lower in the Hypo, Hyper, and sHyper groups than in the NC group (P < 0.01). Compared with the NC group, all four groups had significantly lower residence time in the target quadrant (P < 0.05). Beclin-1 and LC3-II protein expression in hippocampal tissues was significantly higher in the Hyper and sHyper groups than in the NC group (P < 0.01). Beclin-1 and LC3-II protein expression in hippocampal tissues did not significantly differ between the sHypo group and NC group (P > 0.05).
Conclusions: Subclinical thyroid dysfunction in rats might lead to cognitive impairment. Subclinical hyperthyroidism might be associated with excessive activation of autophagy and hippocampal neuron damage and necrosis.

J Nippon Med Sch 2023; 90: 372-380

Keywords
subclinical hyperthyroidism, subclinical hypothyroidism, cognitive impairment, LC3-II, Beclin-1

Correspondence to
Yun-Tian Yang, School of Sport, Exercise and Health Sciences, Loughborough University, Epinal Way, Loughborough, Leicestershire LE11 3TU, United Kingdom
y.yang8@lboro.ac.uk

Received, January 9, 2023
Accepted, April 17, 2023