Thermal cycling-hyperthermia ameliorates cognitive impairment of intracerebroventricular Aβ_25-35-induced Alzheimer’s disease in C57BL/6 mice

Abstract

Despite continuation of some controversies, Alzheimer's disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive β-amyloid (Aβ) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on Aβ 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 Aβ25-35, 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 Aβ 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 Aβ. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into clinical application with the use of high-intensity focused ultrasound (HIFU).