A1 Journal article (refereed)
Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus (2021)

Mäkinen, E., Lensu, S., Honkanen, M., Laitinen, P., Wikgren, J., Koch, L. G., Britton, S. L., Kainulainen, H., Pekkala, S., & Nokia, M. S. (2021). Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus. Brain Behavior and Immunity, 97, 250-259. https://doi.org/10.1016/j.bbi.2021.06.017

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Publication details

All authors or editors: Mäkinen, Elina; Lensu, Sanna; Honkanen, Markus; Laitinen, Paavo; Wikgren, Jan; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki; Pekkala, Satu; Nokia, Miriam S.

Journal or series: Brain Behavior and Immunity

ISSN: 0889-1591

eISSN: 1090-2139

Publication year: 2021

Volume: 97

Pages range: 250-259

Publisher: Elsevier BV

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1016/j.bbi.2021.06.017

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/77814


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.

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.

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.

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: brain; inflammation; hippocampus; cytokines; neuroplasticity; biomarkers; obesity; overweight; metabolism; physical fitness; proteins; neurons; cognition; cognitive skills; genetic factors; hereditary predisposition

Free keywords: cytokines; synaptic proteins; neuroplasticity; neurogenesis

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Ministry reporting: Yes

Reporting Year: 2021

JUFO rating: 1

Last updated on 2023-03-10 at 12:08