Astrocytic tumour necrosis factor underlies neuron function in cognition
Anscomb, H.L., and Baune, B.T. (2010) Astrocytic tumour necrosis factor underlies neuron function in cognition. In: Posters from the Australasian Neuroscience Society Annual Conference. p. 71. From: ANS 2010: Australasian Neuroscience Society Annual Conference, 31 January - 3 February 2010, Sydney, NSW, Australia.
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Abstract
Pro-inflammatory cytokines have been demonstrated to have a diverse range of actions on the functioning of the CNS, and in particular learning and memory behaviours. Details of the mechanisms of action of cytokines are still to be determined.
Purpose: This study uses immunohistochemistry techniques (IHC) to investigate cellular changes present in the hippocampal formation as a result of up-regulation of astrocyte-produced tumour necrosis factor (TNF)α (GFAP-TNFα+/+), prior to onset of behavioural deficits. These findings are compared directly to the hippocampal formation of a TNFα knock-out model (TNFα-/-) in which marked alterations in learning and memory are observed at the same time-point (12 wks) and to age-match wild-type mice (WT). This time period is of critical importance for further elucidating the role of TNFα in hippocampal dependent learning and memory.
Methods: Hippocampi from TNFα-/-, GFAP-TNFα+/+ and WT (n = 5) were subjected to indirect IHC for the analysis of TNFα levels and distribution in regions CA1, CA3 and the dentate gyrus (DG).
Results: In GFAP-TNFα+/+ there was a demonstrated accumulation of TNFα in hippocampal neurons prior to the onset of hippocampal-dependent behavioural deficits. GFAP-TNFα+/+ mice also showed a significant increase in TNFα in regions CA3 and the DG (p = <0.05) when compared to WT and TNFα-/- mice. WT mice demonstrated immunoreactivity of TNFα in regions CA1 and the DG.
Conclusion: These findings suggest that astrocyte-produced TNFα is essential for normal development and functioning of the CA1 region of the hippocampus in cognitive processes. However, an overproduction of astrocytic TNFα accumulates in the neurons of the CA3 and DG regions and likely produces functional deficits, as seen in 6 months plus mice, through these regions.