Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia

Charlton, Tryston; Prowse, Natalie; McFee, Ashley; Heiratifar, Noora; Fortin, T.; Paquette, Caroline; Hayley, Shawn

doi:10.3389/fncel.2023.1188672

Cited by 26 publications

(9 citation statements)

References 45 publications

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“…4 G, H). BDNF has been reported to exhibit direct modulatory effects on LPS-induced inflammation in both microglia and neuronal cultures [ 9 ]. Furthermore, in vivo studies have demonstrated that the administration of pro-inflammatory cytokines or lipopolysaccharide (LPS) significantly reduces mature BDNF levels in brain regions such as the hippocampus and cerebral cortex [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…It plays a critical role in maintaining neuroplasticity and regulating neuronal development, differentiation, and survival. Pro-inflammatory cytokines or lipopolysaccharide (LPS) has been demonstrated to significantly reduce mature BDNF levels in brain regions, including hippocampus [ 9 ]. Recent research has further linked BDNF/TrkB signaling to depression.…”

Section: Introductionmentioning

confidence: 99%

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A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo

Wakasugi,

Kondo,

Ferdousi

et al. 2024

Cell Commun Signal

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Background Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- and anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential in mitigating neuroinflammation and neuroplasticity. Methods In the present study, we aimed to evaluate the neuroprotective effects of oleacein (OC), a rare secoiridoid derivative found in extra virgin olive oil. Our goal was to explore the BDNF/TrkB neurotrophic activity of OC and subsequently assess its potential for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) and an in vivo model of depression induced by lipopolysaccharide (LPS)-mediated inflammation. Results In SH-SY5Y cells, OC exhibited a significant dose-dependent increase in BDNF expression. This enhancement was absent when cells were co-treated with inhibitors of BDNF's receptor TrkB, as well as downstream molecules PI3K and MEK. Whole-transcriptomics analysis revealed that OC upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated genes in LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated that OC exhibited a stronger and more stable binding affinity to TrkB compared to the positive control, 7,8-dihydroxyflavone. Importantly, bioluminescence imaging revealed that a single oral dose of OC significantly increased BDNF expression in the brains of Bdnf-IRES-AkaLuc mice. Furthermore, oral administration of OC at a dosage of 10 mg/kg body weight for 10 days significantly reduced immobility time in the tail suspension test compared to the LPS-treated group. RT-qPCR analysis revealed that OC significantly decreased the expression of pro-inflammatory cytokines Tnfα, Il6, and Il1β, while simultaneously enhancing Bdnf expression, as well as both pro and mature BDNF protein levels in mice hippocampus. These changes were comparable to those induced by the positive control antidepressant drug fluoxetine. Additionally, microarray analysis of mouse brains confirmed that OC could counteract LPS-induced inflammatory biological events. Conclusion Altogether, our study represents the first report on the potential antineuroinflammatory and antidepressant properties of OC via modulation of BDNF/TrkB neurotrophic activity. This finding underscores the potential of OC as a natural therapeutic agent for depression- and anxiety-related disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo

Wakasugi,

Kondo,

Ferdousi

et al. 2024

Cell Commun Signal

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“…Peripheral BDNF concentrations are positively correlated with hippocampal size and cognitive function [196,197]. Similarly, the evidence points to the potential anti-inflammatory properties of BDNF on the brain [198][199][200]. Thus, one may speculate on how mindfulness could increase BDNF in the context of methamphetamine dependency.…”

Section: Neurotrophic and Vascular Effect Of Mindfulness On Neuroplas...mentioning

confidence: 95%

The Effectiveness of Mindfulness in the Treatment of Methamphetamine Addiction Symptoms: Does Neuroplasticity Play a Role?

Chmiel,

Malinowska,

Rybakowski

et al. 2024

Brain Sciences

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Introduction: Methamphetamine is a highly stimulating psychoactive drug that causes life-threatening addictions and affects millions of people around the world. Its effects on the brain are complex and include disturbances in the neurotransmitter systems and neurotoxicity. There are several known treatment methods, but their effectiveness is moderate. It must be emphasised that no drugs have been approved for treatment. For this reason, there is an urgent need to develop new, effective, and safe treatments for methamphetamine. One of the potential treatments is mindfulness meditation. In recent years, this technique has been researched extensively in the context of many neurological and psychiatric disorders. Methods: This review explores the use of mindfulness in the treatment of methamphetamine addiction. Searches were conducted in the PubMed/Medline, Research Gate, and Cochrane databases. Results: Seven studies were identified that used mindfulness-based interventions in the treatment of methamphetamine addiction. The results show that mindfulness is an effective form of reducing hunger, risk of relapses, stress indicators, depression, and aggression, alone or in combination with transcranial direct current stimulation (tDCS). Mindfulness also improved the cognitive function in addicts. The included studies used only behavioural measures. The potential mechanisms of mindfulness in addiction were explained, and it was proposed that it can induce neuroplasticity, alleviating the symptoms of addiction. Conclusions: Evidence from the studies suggest that mindfulness may be an effective treatment option for methamphetamine addiction, used alone or in combination with tDCS. However, further high-quality research is required to establish the role of this treatment option in this field. The use of neuroimaging and neurophysiological measures is fundamental to understand the mechanisms of mindfulness.

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“…Despite previous studies indicating a strong involvement of BDNF in the nociceptive system, its precise role remains uncertain. This uncertainty is further compounded by conflicting findings, with some research indicating a potential anti-inflammatory effect [118][119][120]. For instance, preliminary evidence from animal research suggests that the release of BDNF can alleviate allodynia and hyperalgesia induced by chronic constriction injury [121].…”

Section: Pro-nociceptive and Anti-nociceptive Role Of Bdnfmentioning

confidence: 99%

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation

Xiong,

Hendrix,

Schabrun

et al. 2024

Biomolecules

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Chronic pain is sustained, in part, through the intricate process of central sensitization (CS), marked by maladaptive neuroplasticity and neuronal hyperexcitability within central pain pathways. Accumulating evidence suggests that CS is also driven by neuroinflammation in the peripheral and central nervous system. In any chronic disease, the search for perpetuating factors is crucial in identifying therapeutic targets and developing primary preventive strategies. The brain-derived neurotrophic factor (BDNF) emerges as a critical regulator of synaptic plasticity, serving as both a neurotransmitter and neuromodulator. Mounting evidence supports BDNF’s pro-nociceptive role, spanning from its pain-sensitizing capacity across multiple levels of nociceptive pathways to its intricate involvement in CS and neuroinflammation. Moreover, consistently elevated BDNF levels are observed in various chronic pain disorders. To comprehensively understand the profound impact of BDNF in chronic pain, we delve into its key characteristics, focusing on its role in underlying molecular mechanisms contributing to chronic pain. Additionally, we also explore the potential utility of BDNF as an objective biomarker for chronic pain. This discussion encompasses emerging therapeutic approaches aimed at modulating BDNF expression, offering insights into addressing the intricate complexities of chronic pain.

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Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia

Cited by 26 publications

References 45 publications

A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo

A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo

The Effectiveness of Mindfulness in the Treatment of Methamphetamine Addiction Symptoms: Does Neuroplasticity Play a Role?

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation

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