High-intensity interval training ameliorates spatial and recognition memory impairments, reduces hippocampal TNF-alpha levels, and amyloid-beta peptide load in male hypothyroid rats

Thyroid hormones are critical for healthy brain functions at every stage of life. Hypothyroidism can cause severe cognitive dysfunction in patients who do not receive adequate treatment. Although thyroid hormone replacement alleviates cognitive decline in hypothyroid patients, there are studies showing that there is no complete recovery. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) in hypothyroid rats on spatial and recognition memory, neuroinflammation, amyloid-beta load and compare these effects with T3 replacement. Hypothyroidism was induced and maintained by administration of 6-n-propyl-2-thiouracil (PTU) with their drinking water to 6-weeks-old male Sprague-Dawley rats for 7 weeks. The animals exercised in the treadmill according to the HIIT protocol for four weeks. T3 was injected intraperitoneally daily during the last two weeks of the study. All animals performed in the elevated plus maze test, Morris water maze test, novel object recognition test, and rotarod motor performance test in the last week of the study and then the animals were sacrificed. Amyloid beta (1-42) and TNF alpha levels were measured in the prefrontal cortex and hippocampus by ELISA. Anxiety-like behaviors did not significantly differ between groups. T3 replacement with or without HIIT increased motor performance in PTU-treated rats. HIIT and/or T3 replacement increased the exercise performance. HIIT and/or T3 replacement alleviated spatial and recognition memory impairments and normalized TNF alpha and amyloid-beta levels in the hippocampus in hypothyroid rats. In summary, regular physical exercise may have potential benefits in preserving cognitive functions in hypothyroid patients.