Thermal cycling-hyperthermia ameliorates Aβ25-35-induced cognitive impairment in C57BL/6 mice

Yu-Yi Kuo; Wei-Ting Chen; Guan-Bo Lin; You-Ming Chen; Hsu-Hsiang Liu; Chih-Yu Chao

doi:10.1016/j.neulet.2023.137337

Thermal cycling-hyperthermia ameliorates Aβ_25-35-induced cognitive impairment in C57BL/6 mice

Neurosci Lett. 2023 Jul 27:810:137337. doi: 10.1016/j.neulet.2023.137337. Epub 2023 Jun 12.

Authors

Yu-Yi Kuo¹, Wei-Ting Chen¹, Guan-Bo Lin¹, You-Ming Chen², Hsu-Hsiang Liu², Chih-Yu Chao³

Affiliations

¹ Department of Physics, Lab for Medical Physics & Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan; Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
² Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 10051, Taiwan; Graduate Institute of Applied Physics, Biophysics Division, National Taiwan University, Taipei 10617, Taiwan.
³ Department of Physics, Lab for Medical Physics & Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan; Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 10051, Taiwan; Graduate Institute of Applied Physics, Biophysics Division, National Taiwan University, Taipei 10617, Taiwan. Electronic address: cychao@phys.ntu.edu.tw.

PMID: 37315732
DOI: 10.1016/j.neulet.2023.137337

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) to ease the Aβ-induced cognitive impairments and compared its effect with continuous hyperthermia (HT) in vivo. It established an AD mice model via intracerebroventricular (i.c.v.) injection of Aβ_25-35, proving that TC-HT is much more effective in alleviating its performance decline in Y-maze and novel object recognition (NOR) tests, in comparison with HT. In addition, TC-HT also exhibits a better performance in decreasing the hippocampal Aβ and β-secretase (BACE1) expressions as well as the neuroinflammation markers-ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) levels. Furthermore, the study finds that TC-HT can elevate more protein expressions of insulin degrading enzyme (IDE) and antioxidative enzyme superoxide dismutase 2 (SOD2) than HT. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into application with the use of focused ultrasound (FUS).

Keywords: Anti-neuroinflammation; Antioxidation; Hyperthermia; Neurodegenerative disease; β-amyloid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Alzheimer Disease* / therapy
Amyloid Precursor Protein Secretases
Amyloid beta-Peptides / metabolism
Amyloid beta-Peptides / toxicity
Animals
Aspartic Acid Endopeptidases
Cognitive Dysfunction* / drug therapy
Cognitive Dysfunction* / therapy
Disease Models, Animal
Hyperthermia, Induced*
Mice
Mice, Inbred C57BL
Neuroinflammatory Diseases

Substances

Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Amyloid beta-Peptides