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Cachexia in mice blunts improved cognitive flexibility induced by calorie restriction.
Kyna Conn1, Laura Milton1, Alyssa Teoh1
1Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
Brain, Behavior, and Immunity
|September 29, 2025
Summary
Cancer-related cachexia impairs cognitive flexibility more than calorie restriction alone. Pancreatic cancer mice showed reduced task performance, unlike calorie-restricted mice, suggesting sickness impacts brain function differently.
Area of Science:
- Neuroscience
- Oncology
- Metabolic Syndrome
Background:
- Cachexia affects 50-80% of cancer patients, involving inflammation, appetite loss, and muscle wasting.
- Cancer cachexia is linked to more severe cognitive impairment, but studying this in humans is difficult.
Purpose of the Study:
- To investigate cognitive performance in a mouse model of pancreatic cancer (PDAC) cachexia.
- To differentiate cognitive effects of cancer cachexia from those of calorie restriction.
Main Methods:
- Used an in-cage operant device (FED3) and a reversal learning task in PDAC mice, ad libitum fed (PBS), and calorie-restricted (CR) mice.
- Administered lithium chloride (LiCl) to CR mice to mimic sickness and assessed anxiety-like behaviors using maze tests.
Main Results:
- PDAC mice showed impaired cognitive flexibility compared to CR mice, with no difference between PDAC and PBS groups.
- Sickness induced by LiCl reduced reward-seeking behavior, suggesting sickness-induced devaluation of reward.
- No significant differences in anxiety-like behaviors were observed between PDAC and PBS groups.
Conclusions:
- Cancer cachexia specifically impacts cognitive flexibility, distinct from weight loss due to calorie restriction.
- Sickness, not just weight loss, may be a key factor in cognitive deficits associated with cancer.
- Elevated pro-cachexia factors (GDF15, Activin A/B) were not sufficient to induce behavioral changes in anxiety tests.
