Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats
Abstract
Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, induces neuronal death, decreases neurogenesis, and impairs synaptic plasticity and memory, but the mechanisms for these effects are not well understood. We hypothesize that neurotrophin levels in the brain are influenced by LPS. To test this hypothesis, we determined effects of LPS on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and NT-3 levels in the brain after intraperitoneal injection of saline or LPS (0.1, 0.3 or 1.0mg/kg) in rats. LPS significantly decreased BDNF in the hippocampus (-20%), frontal cortex (-19%), parietal cortex (-63%), temporal cortex (-29%), and occipital cortex (-41%). LPS also significantly decreased NGF levels by 10-20% in the hippocampus and different cortical regions, except in the occipital cortex. Finally, LPS decreased NT-3 by 15-25% in the frontal cortex. These observations indicate that the neuroprotection mediated by neurotrophins in the brain are compromised by systemic immune activation induced by LPS.
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Increased pro-inflammatory signaling leads to a reduction in the mRNA expression of Bdnf and other neurotrophins in plasticity-related brain structures, especially cortical regions.
“Increased pro-inflammatory signaling leads to a reduction in the mRNA expression of Bdnf and other neurotrophins in plasticity-related brain structures, especially cortical regions [75].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [75]
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- Authors
- Guan, Z., & Fang, J.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Fang, Jidong
- ORCID
- Guan, Zhiwei
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 20
- Issue
- 1
- Pages
- 64-71
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2003123811
- Cited by
- 247
- References
- 58
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 8 · 2023: 16 · 2022: 10 · 2021: 16 · 2020: 14 · 2019: 19 · 2018: 21 · 2017: 26 · 2016: 24 · 2015: 12 · 2014: 15 · 2013: 8 · 2012: 11
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 64245, R01HL064245)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- lipopolysaccharide, neurotrophins, brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, neuroinflammation, peripheral immune activation, hippocampus, cerebral cortex, neuroprotection, neurogenesis, synaptic plasticity
- MeSH terms
- Animals, Cerebral Cortex, Hippocampus, Injections, Intraperitoneal, Lipopolysaccharides, Lymphocyte Activation, Male, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Neurotrophin 3, Rats
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