Immune-mediated regulation of Neurotrophins: a role for TNF

Camara, Marie, Jaehne, Emily, Jawahar, Magdalene, Corrigan, Frances, Anscomb, Helen, Korner, Heinrich, and Baune, Bernhard (2012) Immune-mediated regulation of Neurotrophins: a role for TNF. In: 4th Brain Plasticity Symposium. From: QBI 4th Brain Plasticity Symposium. Circuits, Synapses and Behaviour, 3-5 September 2012, Queensland Brain Institute, Brisbane. (Unpublished)

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Neurogenesis is an important process regulating learning and memory, with neurotrophic factors like Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) essential to neurogenesis in the central nervous system. Recent evidence points to the role of immune mediators, particularly the cytokine tumor necrosis factor alpha (TNF) in the regulation and expression of neurotrophins. TNF signals through two main receptor subtypes - TNF-R1 and TNF-R2, with the TNF-R1 pathway seen as neurodegenerative and the TNF-R2 pathway as neuroproliverative. Previous studies have indicated that TNF regulates the expression of BDNF and NGF; however the exact mechanisms of this have not been clearly elucidated leaving the relative involvement of the TNF-R1 and TNF-R2 signalling pathways unknown. Therefore the aim of this study was to elucidate the mechanisms through which TNF exerts its influence on neurotrophins and how this affects learning and memory. The study used genetically modified 3 month old mice, (n=14 per strain), in TNF-/-, TNF-R1-/- andTNF-R2-/-, as well as wild type control mice on a B.6 background. The mice were subject to a behavioural battery incorporating the Barnes Maze to measure cognition like behaviour and Elevated Zero Maze to assess anxiety. An ELISA was then performed on hippocampal and prefrontal cortex tissue (n=7 per strain) to assess the amount of BDNF and NGF expressed in these areas. Cognitive deficits were seen in TNF-KO, TNF-R1 KO and TNF-R2 KO mice on the Barnes Maze with an increase in time taken to learn the location of the escape box compared to WT mice. Furthermore, increased anxiety was observed in these strains as measured by the Elevated Zero Maze (p<0.001). ELISA data revealed low levels of NGF in TNF-KO and TNF-R2 KO mice, while low levels of BDNF were observed in the TNF-R2 KO mice. In contrast, neither NGF nor BDNF levels were altered in TNF-R1-/- mice. These results indicate that constitutional levels of TNF are required for normal learning and involve signalling via both the TNFR1-/- and TNFR2-/- pathways. The impairment in cognition in TNF KO and TNF-R2 KO mice was accompanied by changes in neurotophin levels indicating this may be a potential mechanism whereby TNF regulates cognition and behaviour. Interestingly signalling via TNF-R1 also impaired cognition, but was not associated with changes in neurotrophins, with further studies needed to determine how this primarily neurodegenerative pathway is necessary for normal learning.

Item ID: 40990
Item Type: Conference Item (Poster)
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Date Deposited: 24 Oct 2016 23:37
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 @ 100%
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