Tumor necrosis factor alpha and its receptors in behaviour and neurobiology of adult mice, in the absence of an immune challenge

Camara, Marie Lou, Corrigan, Frances, Jaehne, Emily J., Jawahar, M. Catharine, Anscomb, Helen, and Baune, Bernhard T. (2015) Tumor necrosis factor alpha and its receptors in behaviour and neurobiology of adult mice, in the absence of an immune challenge. Behavioural Brain Research, 290. pp. 51-60.

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Abstract

Tumor necrosis factor alpha (TNF-α) is a vital component of the immune system and CNS. We previously showed that 3-month-old TNF-α and TNF-α receptor knockout mice had impaired cognition, whilst at 12-months-old mice had better cognition. To extend these findings on possible age-dependent TNF-α effects in the brain, we investigated the behaviour of 6-month-old TNF-α knockout mice and their neurobiological correlates. 6-month-old TNF−/−, TNF-R1−/− and TNF-R2−/− mice were compared to age-matched WT mice and tested for various behaviours. ELISA hippocampal levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) and qPCR mRNA levels of Tnfa, Tnfr1, Tnfr2, Il10 and Il1β were measured. TNF-R1−/− and TNF−/− mice were found to have lesser exploratory behaviour than WT mice, while TNF-R1−/− mice displayed better memory than WT and TNF-R2-/− mice. Both TNF−/− and TNF-R2−/− mice exhibited significantly lower immobility on the depression test than WT mice. Additionally, TNF−/− mice expressed significantly lower levels of BDNF than WT mice in the hippocampus while TNF-R1−/− mice displayed significantly lower BDNF levels compared to both WT and TNF-R2−/− mice. TNF-R2−/− mice also displayed significantly higher levels of NGF compared to TNF-R1−/− mice. These results illustrate that TNF-α and its receptors mediate several behavioural phenotypes. Finally, BDNF and NGF levels appear to be regulated by TNF-α and its receptors even under immunologically unchallenged conditions.

Item ID: 40194
Item Type: Article (Research - C1)
ISSN: 1872-7549
Keywords: TNF-α; cognition; depression; neurotrophins; TNF-α receptor
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC APP1003788 to BTB
Date Deposited: 04 Sep 2015 02:48
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 50%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920401 Behaviour and Health @ 25%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 25%
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