TNF signalling via the TNF receptors mediates the effects of exercise on cognition-like behaviours

Julie A Morgan; Gaurav Singhal; Frances Corrigan; Emily J Jaehne; Magdalene C Jawahar; Bernhard T Baune

doi:10.1016/j.bbr.2018.06.036

TNF signalling via the TNF receptors mediates the effects of exercise on cognition-like behaviours

Behav Brain Res. 2018 Nov 1:353:74-82. doi: 10.1016/j.bbr.2018.06.036. Epub 2018 Jun 30.

Authors

Julie A Morgan¹, Gaurav Singhal¹, Frances Corrigan², Emily J Jaehne³, Magdalene C Jawahar¹, Bernhard T Baune⁴

Affiliations

¹ The University of Adelaide, School of Medicine, Discipline of Psychiatry, Adelaide, Australia.
² The University of Adelaide, School of Medicine, Discipline of Medical Sciences, Adelaide, Australia.
³ The University of Adelaide, School of Medicine, Discipline of Psychiatry, Adelaide, Australia; La Trobe University, School of Psychology and Public Health, Melbourne, Australia.
⁴ The University of Adelaide, School of Medicine, Discipline of Psychiatry, Adelaide, Australia. Electronic address: Bernhard.Baune@adelaide.edu.au.

PMID: 29969604
DOI: 10.1016/j.bbr.2018.06.036

Abstract

Background: Altered TNF levels are associated with cognitive impairment in depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). Exercise improves cognition-like behaviours, reduces the expression of tumour necrosis factor alpha (TNF), and increases expression of the soluble TNF receptors soluble TNFR1 (sTNFR1) and sTNFR2. We suggest TNF and its receptors are involved in cognitive function and dysfunction, and investigate whether exercise mediates its effects on cognitive function via TNF and its receptors.

Methods: We utilised C57BL/6, TNF^-/-, TNFR1^-/-, and TNFR2^-/- mice to compare exercise to non-exercise control groups to investigate whether exercise exerts its effects on various types of cognition-like behaviours via TNF and its receptors.

Results: Recognition memory improved with exercise in WT mice, was impaired in TNFR1^-/- exercise mice, showed non-significant impairment with exercise in TNF^-/- mice, and no changes in TNFR2^-/- mice. In spatial learning there were exercise related improvements in WT mice, non-significant but meaningful impairments evident in TNFR1^-/- exercise mice, modest improvement in TNF^-/- exercise mice, and potentially meaningful non-significant improvements in TNFR2^-/- exercise mice. Moreover, WT and TNFR2^-/- mice displayed noteworthy non-significant improvements in spatial memory, whereas TNFR1^-/- exercise mice demonstrated non-significant spatial memory impairment. Exercise did not alter cognitive flexibility in any strain.

Discussion: TNF receptor signalling via the TNFR1 and TNFR2 appears to mediate the effects of exercise on cognitive-like behaviours. The potential for exercise to regulate human TNF and TNF signalling and cognitive dysfunction needs investigation under inflammatory conditions including depression and neuropsychiatric disorders.

Keywords: Animal model; Cognition; Exercise; Tumour necrosis factor receptor 1; Tumour necrosis factor receptor 2; Tumour necrosis factor-alpha.

Publication types

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

MeSH terms

Animals
Behavior, Animal / physiology
Cognition / physiology*
Executive Function / physiology
Female
Male
Maze Learning / physiology
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / physiology*
Random Allocation
Receptors, Tumor Necrosis Factor, Type I / genetics
Receptors, Tumor Necrosis Factor, Type I / metabolism*
Receptors, Tumor Necrosis Factor, Type II / genetics
Receptors, Tumor Necrosis Factor, Type II / metabolism*
Recognition, Psychology / physiology
Signal Transduction
Spatial Memory / physiology
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism*

Substances

Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tnfrsf1a protein, mouse
Tumor Necrosis Factor-alpha