Journal
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
Volume 64, Issue -, Pages 134-147Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2016.02.013
Keywords
Innate immunity; Toll-like receptors; Inflammation; Stress; Schizophrenia; Depression
Categories
Funding
- Univ. Complutense de Madrid
- Spanish Ministries of Science and Innovation and of Economy
- Autonomous Governments of Madrid (CannabCM)
- Foundation Mutua Madrilefia
- Foundation Alicia Koplowitz
Ask authors/readers for more resources
The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The leaky gut hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. (C) 2016 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available