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Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

  • Review Article
  • Published:
Translational Neuroscience

Abstract

Background

Tumour necrosis factor - alpha (TNF-α) is a pro-inflammatory cytokine that combines a plethora of activities in the early stages of an immune response. TNF-α has gained increasing importance given TNF-α upregulation in multiple brain pathologies like neuropsychiatric conditions such as depression, schizophrenia, as well as neuroinflammatory disorder like multiple sclerosis (MS).

Aim

The aim of this review is to critically analyse neurobiological, immunological and molecular mechanisms through which TNF-α influences the development of cognitive dysfunction.

Principal findings/results

The review presents several lines of original research showing that the immunological properties of TNF-α exacerbate inflammatory responses in the central nervous system such as microglial and endothelial activation, lymphocytic and monocytic infiltration and the expression of downstream pro-inflammatory cytokines and apoptotic factors. Depression, schizophrenia, and MS all manifest symptoms of activated immune response along with cognitive dysfunction, with TNF-α overexpression as a central clinical feature common to these disorders. Furthermore, TNF-α acts negatively on neuroplasticity and the molecular mechanisms of memory and learning (i.e., long-term potentiation and long-term depression). TNF-α also exerts influence over the production of neurotrophins (i.e., nerve growth factor and brain-derived neurotrophic factor), neurogenesis, and dendritic branching.

Conclusions/significance

This review outlines that TNF-α and its receptors have a substantial yet underappreciated influence on the development and progression of neuropsychiatric symptoms across several disease entities. An improved understanding of these underlying mechanisms may help develop novel therapeutic targets in the form of drugs specifically targeting downstream products of TNF-α activation within the central nervous system.

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Authors and Affiliations

  1. Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia

    Bernhard T. Baune, Marie-Lou Camara, Harris Eyre & Catharine Jawahar

  2. Discipline of Anatomy, School of Medicine, James Cook University, Townsville, QLD, Australia

    Helen Anscomb

  3. Cellular Immunology Laboratory, Menzies Research Institute Tasmania, Hobart, Tasmania, Australia

    Heinrich Körner

  4. Psychiatry and Psychiatric Neuroscience, School of Medicine, James Cook University, Townsville, QLD, Australia

    Marie-Lou Camara & Harris Eyre

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  1. Bernhard T. Baune
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  2. Marie-Lou Camara
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  4. Catharine Jawahar
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  5. Helen Anscomb
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  6. Heinrich Körner
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Correspondence to Bernhard T. Baune.

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These authors should be regarded as joint first authors as they have contributed equally to the manuscript.

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Baune, B.T., Camara, ML., Eyre, H. et al. Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction. Translat.Neurosci. 3, 263–277 (2012). https://doi.org/10.2478/s13380-012-0027-8

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