Brain tumor necrosis factor-α mediates anxiety-like behavior in a mouse model of severe obesity

Fourrier, Célia; Bosch‐Bouju, Clémentine; Boursereau, R.; Sauvant, Julie; Aubert, Agnès; Capuron, Lucile; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

doi:10.1016/j.bbi.2018.11.316

Cited by 46 publications

(33 citation statements)

References 90 publications

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“…However, our data show that although PC1 has a strong ability to normalize altered mRNA levels of most neuroinflammatory markers evaluated it was unable to significantly oppose to TNF-α increase in the hippocampus. Considering the crucial role of this cytokine in anxiety [ 56 , 57 ], we can speculate that the high hippocampal TNF-α levels can contribute to sustain an anxiety behavior in BTZ mice.…”

Section: Discussionmentioning

confidence: 99%

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

Amodeo

Verduci

Sartori

et al. 2021

IJMS

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The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL-6 and TNF-α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression-like behavior in BTZ mice.

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Section: Discussionmentioning

confidence: 99%

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

Amodeo

Verduci

Sartori

et al. 2021

IJMS

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“…In fact, HFD mice express higher levels of IL1β in comparison with WT mice fed with chow diet [108]. The levels of TNFα are reduced in the hippocampus and in different areas of the brain of db/db mice [123]. SCFAs, produced by commensal dietary fiber-fermenting microbes characterizing healthy and lean individuals, induce the biosynthesis of leptin in adipocytes through the activation of GPR41 and subsequent leptin-mediated signaling [124].…”

Section: Inflammatory Cytokine Signalingmentioning

confidence: 99%

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Forte

Fernández-Rilo

Palomba

et al. 2020

IJMS

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The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota–gut–brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the “expanded endocannabinoid (eCB) system” or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.

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“…5 A and Additional file 7 : Fig. S3A) [ 49 , 54 ]. Accordingly, the HC inflammatory z -score (integrating data from inflammatory factors displayed in Fig.…”

Section: Resultsmentioning

confidence: 99%

A new experimental design to study inflammation-related versus non-inflammation-related depression in mice

Cardinal

Oliveira

Sauvant

et al. 2021

J Neuroinflammation

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Background Major depressive disorder (MDD) represents a major public health concern, particularly due to its steadily rising prevalence and the poor responsiveness to standard antidepressants notably in patients afflicted with chronic inflammatory conditions, such as obesity. This highlights the need to improve current therapeutic strategies, including by targeting inflammation based on its role in the pathophysiology and treatment responsiveness of MDD. Nevertheless, dissecting the relative contribution of inflammation in the development and treatment of MDD remains a major issue, further complicated by the lack of preclinical depression models suitable to experimentally dissociate inflammation-related vs. inflammation-unrelated depression. Methods While current models usually focus on one particular MDD risk factor, we compared in male C57BL/6J mice the behavioral, inflammatory and neurobiological impact of chronic exposure to high-fat diet (HFD), a procedure known to induce inflammation-related depressive-like behaviors, and unpredictable chronic mild stress (UCMS), a stress-induced depression model notably renowned for its responsivity to antidepressants. Results While both paradigms induced neurovegetative, depressive-like and anxiety-like behaviors, inflammation and downstream neurobiological pathways contributing to inflammation-driven depression were specifically activated in HFD mice, as revealed by increased circulating levels of inflammatory factors, as well as brain expression of microglial activation markers and enzymes from the kynurenine and tetrahydrobiopterin (BH4) pathways. In addition, serotoninergic and dopaminergic systems were differentially impacted, depending on the experimental condition. Conclusions These data validate an experimental design suitable to deeply study the mechanisms underlying inflammation-driven depression comparatively to non-inflammatory depression. This design could help to better understand the pathophysiology of treatment resistant depression.

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Brain tumor necrosis factor-α mediates anxiety-like behavior in a mouse model of severe obesity

Cited by 46 publications

References 90 publications

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

A new experimental design to study inflammation-related versus non-inflammation-related depression in mice

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