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      Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation

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          Abstract

          Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

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          Most cited references168

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          Inflammation is implicated in the progressive nature of neurodegenerative diseases, such as Parkinson's disease, but the mechanisms are poorly understood. A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFalpha, 0.25 mg/kg, i.p.) injection was administered in adult wild-type mice and in mice lacking TNFalpha receptors (TNF R1/R2(-/-)) to discern the mechanisms of inflammation transfer from the periphery to the brain and the neurodegenerative consequences. Systemic LPS administration resulted in rapid brain TNFalpha increase that remained elevated for 10 months, while peripheral TNFalpha (serum and liver) had subsided by 9 h (serum) and 1 week (liver). Systemic TNFalpha and LPS administration activated microglia and increased expression of brain pro-inflammatory factors (i.e., TNFalpha, MCP-1, IL-1beta, and NF-kappaB p65) in wild-type mice, but not in TNF R1/R2(-/-) mice. Further, LPS reduced the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra (SN) by 23% at 7-months post-treatment, which progressed to 47% at 10 months. Together, these data demonstrate that through TNFalpha, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated pro-inflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self-propelling nature of Parkinson's disease. (c) 2007 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                e.f.j.de.vries@umcg.nl
                Journal
                Mol Neurobiol
                Mol. Neurobiol
                Molecular Neurobiology
                Springer US (New York )
                0893-7648
                1559-1182
                17 August 2018
                17 August 2018
                2019
                : 56
                : 5
                : 3295-3312
                Affiliations
                [1 ]ISNI 0000 0001 2166 9094, GRID grid.412519.a, Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, , Pontifical Catholic University of Rio Grande do Sul, ; Ipiranga Av. 6681, Porto Alegre, 90619-900 Brazil
                [2 ]ISNI 0000 0000 9558 4598, GRID grid.4494.d, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, , University Medical Center Groningen, ; Hanzeplein 1, P.O. Box 31.001, 9713 GZ Groningen, The Netherlands
                Author information
                http://orcid.org/0000-0002-6915-1590
                Article
                1283
                10.1007/s12035-018-1283-6
                6476855
                30117106
                3a3acff9-29da-4b4a-8b66-742dd6af0916
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 8 March 2018
                : 24 July 2018
                Funding
                Funded by: University Medical Center Groningen (UMCG)
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2019

                Neurosciences
                brain-derived neurotrophic factor,neuroinflammation,neurological disorders,neurotoxicity

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