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A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

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Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice.

Samuel A McFadden¹, Mackenzie R Peck¹, Lindsey N Sime¹

¹Department of Neurology, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Neurosciences Institute, Springfield, IL, USA.

Biorxiv : the Preprint Server for Biology

|April 8, 2024

Summary

Elevating body temperature with thermotherapy improved metabolism and spatial navigation in male mice, including those with Alzheimer's disease. However, female mice with Alzheimer's showed impaired memory recall, indicating sex-specific effects.

Keywords:

Alzheimer’s disease cognition core body temperature glucose tolerance insulin sensitivity metabolism

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Published on: July 27, 2022

Area of Science:

Neuroscience
Metabolism
Aging

Background:

Aging is associated with decreased core body temperature (Tc), impacting muscle mass, vasoconstriction, and metabolism.
Lower Tc, while a biomarker of successful aging, has been shown to worsen cognitive performance in Alzheimer's disease (AD) models.

Purpose of the Study:

To investigate if elevating Tc through thermotherapy improves metabolism and cognition in the APP/PS1 mouse model of AD.
To explore sex-specific differences in response to chronic thermotherapy in relation to metabolism and cognition.

Main Methods:

APP/PS1 and C57BL/6 mice (males and females) were housed at 23°C or 30°C from 6-12 months of age.
Assays included insulin sensitivity, glucose tolerance, spatial cognition, and tissue-specific markers of amyloid, metabolism, and inflammation.
Core body temperature (Tc) was monitored, and plasma, hippocampal, and peripheral tissue samples were analyzed postmortem.

Main Results:

Chronic thermotherapy (30°C) increased Tc in most groups, except female APP/PS1 mice.
Thermotherapy improved glucose tolerance or insulin sensitivity across sexes, with sex-specific underlying mechanisms observed.
Spatial navigation improved in male mice (both wild-type and APP/PS1), linked to reduced hippocampal amyloid-beta in APP/PS1 males.
Female APP/PS1 mice showed worsened spatial memory recall after thermotherapy.

Conclusions:

Passive thermotherapy demonstrates metabolic benefits, with sex-specific variations in glucose regulation pathways.
Therapeutic benefits for AD are complex; while male APP/PS1 mice showed cognitive improvements, female APP/PS1 mice experienced cognitive decline.
Further research is required to elucidate the therapeutic potential of thermotherapy for Alzheimer's disease, considering sex differences.