Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus

Elina Mäkinen; Sanna Lensu; Markus Honkanen; Paavo Laitinen; Jan Wikgren; Lauren G Koch; Steven L Britton; Heikki Kainulainen; Satu Pekkala; Miriam S Nokia

doi:10.1016/j.bbi.2021.06.017

Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus

Brain Behav Immun. 2021 Oct:97:250-259. doi: 10.1016/j.bbi.2021.06.017. Epub 2021 Jul 2.

Authors

Affiliations

¹ Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland. Electronic address: elina.e.makinen@jyu.fi.
² Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland; Department of Psychology, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland.
³ Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland.
⁴ Department of Psychology, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland.
⁵ Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, The University of Toledo College of Medicine & Life Sciences, Toledo, OH, 2801 W. Bancroft, Toledo, OH 43606-3390, USA.
⁶ Department of Anesthesiology, University of Michigan, Ann Arbor, 1500 E Medical Center Drive, Ann Arbor, MI 48109-5048, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, 7744 MS II, 1137 E, Catherine St., Ann Arbor, MI 48109-5622, USA.

PMID: 34224822
DOI: 10.1016/j.bbi.2021.06.017

Abstract

Background: Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats.

Methods: We examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins.

Results: Our study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones.

Conclusion: Our study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.

Keywords: Cytokines; Neurogenesis; Neuroplasticity; Synaptic proteins.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adiposity
Animals
Encephalitis*
Exercise Tolerance
Hippocampus
Obesity / complications
Physical Conditioning, Animal*
Rats

Grants and funding

P40 OD021331/OD/NIH HHS/United States