Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

Baune, Bernhard, Camara, Marie-Lou, Eyre, Harris, Jawahar, Catherine, Anscomb, Helen, and Korner, Heinrich (2012) Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction. Translational Neuroscience, 3 (3). pp. 263-277.

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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.

Item ID: 25274
Item Type: Article (Research - C1)
ISSN: 2081-6936
Keywords: tumour necrosis factor alpha, cytokines, neuropsychiatry, neuroinflammation, depression, neuroplasticity, neurotrophins
Additional Information:

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License

Date Deposited: 05 Mar 2013 06:14
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110319 Psychiatry (incl Psychotherapy) @ 70%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
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