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bioRxiv · 10.1101/2022.07.22.500895

Thermal cycling-hyperthermia ameliorates cognitive impairment of intracerebroventricular Aβ25-35-induced Alzheimer's disease in C57BL/6 mice

Kuo, Y.-Y.·Chen, W.-T.·Lin, G.-B.·Chen, Y.-M.·Liu, H.-H.·Chao, C.-Y.
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Abstract

Despite continuation of some controversies, Alzheimers disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive {beta}-amyloid (A{beta}) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on A{beta} have been ineffective or offer only temporary relief at best, due to blood-brain barrier or severe side effects. The study employed thermal cycling-hyperthermia (TC-HT) as an alternative AD therapy and compared its effect with continuous hyperthermia (HT) in vivo. It established an AD mice model via intracerebroventricular (i.c.v.) injection of A{beta}25-35, proving that TC-HT is much more effective in alleviating its performance decline in Y-maze and NOR test, in comparison with HT. In addition, TC-HT also exhibits a better performance in decreasing the hippocampal A{beta} and BACE1 expressions as well as the neuroinflammation markers Iba-1 and GFAP levels. Furthermore, the study finds that TC-HT can elevate more protein expressions of IDE and antioxidative enzyme SOD2 than HT. Besides, after establishment of neuroprotective mechanism, removal of TC-HT-induced ROS can further augment protection of neural cells against A{beta}. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into clinical application with the use of focused ultrasound (FUS).

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Kuo, Y.-Y., Chen, W.-T., Lin, G.-B., Chen, Y.-M., Liu, H.-H., Chao, C.-Y.. 2022-07-23. Thermal cycling-hyperthermia ameliorates cognitive impairment of intracerebroventricular Aβ25-35-induced Alzheimer's disease in C57BL/6 mice. https://doi.org/10.1101/2022.07.22.500895

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