Systemic TNF-α blockade attenuates anxiety and depressive-like behaviors in db/db mice through downregulation of inflammatory signaling in peripheral immune cells

Alshammari, Musaad A.; Khan, Mohammad Rashid; Mahmood, Hafiz Majid; Alshehri, Abdulaziz O; Alasmari, Fawaz; Alqahtani, Faleh; Alasmari, Abdullah F.; AlSharari, Shakir D.; Alhossan, Abdulaziz; Ahmad, Sheikh F.; Nadeem, Ahmed; Alshammari, Tahani K.

doi:10.1016/j.jsps.2020.04.001

Cited by 23 publications

(17 citation statements)

References 70 publications

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“…A previous study reported that anxiety-like behavior in obese mice was associated with increased levels of TNF-α, IL-1β, and IL-6 in the brain [62]. In contrast, treatment with TNF-α and IL-1β inhibitors could suppress the development of anxiety in mouse models [63,64]. In the current study, elevated levels of proinflammatory molecules TNF-α and IL-1β were observed in the prefrontal cortex of IMQ-induced psoriasis mice.…”

Section: Discussionsupporting

confidence: 43%

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice

et al. 2022

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Psoriasis is a common inflammatory skin disorder, which can be associated with psychological disorders, such as anxiety and depression. This study investigated the efficacy and the mechanism of action of a natural compound coptisine using imiquimod (IMQ)-induced psoriasis mice. Coptisine reduced the severity of psoriasis-like skin lesions, decreased epidermal hyperplasia and the levels of inflammatory cytokines TNF-α, IL-17, and IL-22. Furthermore, coptisine improved IMQ-induced anxiety in mice by increasing the number of entries and time in open arms in the elevated plus maze (EPM) test. Coptisine also lowered the levels of inflammatory cytokines TNF-α and IL-1β in the prefrontal cortex of psoriasis mice. HaCaT keratinocytes and BV2 microglial cells were used to investigate the effects of coptisine in vitro. In M5-treated HaCaT cells, coptisine decreased the production of IL-6, MIP-3α/CCL20, IP-10/CXCL10, and ICAM-1 and suppressed the NF-κB signaling pathway. In LPS-stimulated BV2 cells, coptisine reduced the secretion of TNF-α and IL-1β. These findings suggest that coptisine might be a potential candidate for psoriasis treatment by improving both disease severity and psychological comorbidities.

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Section: Discussionsupporting

confidence: 43%

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice

et al. 2022

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“…TNF-α plays a vital role in the progression of cognitive decline as well as anxiety [ 19 ]; targeting TNF-α signaling was effective in modulating anxiety in mice [ 20 ]. Thus, we evaluated correlations between the parameters of anxiety and the Tnf mRNA levels in both the OB and FC of WT and 5 × FAD young male mice.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Anxiety and Olfactory Microglial Activation in Early-Stage Familial Alzheimer’s Disease Mouse Model

Chithanathan

Xuan

Hickey

et al. 2022

Biology

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Anxiety is a known comorbidity and risk factor for conversion to neuroinflammation-mediated dementia in patients with Alzheimer’s disease (AD). Here, we investigated if anxiety occurred as an early endophenotype of mutant familial AD (5 × FAD) male mice and the underlying neuroinflammatory mechanisms. We observed that compared to wildtype (WT) littermates, 5 × FAD mice showed enhanced anxiety at as early as 2 months old (mo). Interestingly, these 5 × FAD male mice had concomitantly increased mRNA levels of pro-inflammatory cytokines such as interleukin 1 beta (Il1b) and tumor necrosis factor (Tnf) in the olfactory bulb (OB) but not the frontal cortex (FC). Increased expression of Tnf in the OB was significantly correlated with the anxious behavior in the FAD but not WT mice. Furthermore, we found more prominent microglial activation and morphological changes in the OB of 2 mo 5 × FAD mice, while only microglial ramification was seen in the FC. To understand if neuroinflammatory changes in the FC could occur at a later stage, we studied 5~6 mo male mice and found that Il1b, interleukin 18 (Il18), and Tnf were upregulated in the FC at this older age. Furthermore, we observed that numbers of microglia and macrophage as well as microglial synaptic pruning, as indicated by phagocytosis of presynaptic component of vesicular glutamate transporter-2, were increased in the OB but not the FC of 5~6 mo 5 × FAD mice. Our findings demonstrated the OB as a more sensitive brain region than the cerebral cortex for microglia-mediated neuroinflammation in association with anxiety in FAD mice and supported the notion that the OB can be an early-stage biomarker in AD.

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“…More recently, a study in rats showed that etanercept significantly decreased depressive-like behavior and improved cognitive function [ 158 ]. Similarly, a study in mice showed that etanercept exerted a potent antidepressant-like effect and an anxiolytic-like effect [ 159 ]. In line with these pre-clinical results, etanercept was found to significantly decrease the severity of fatigue, depression and anxiety symptoms among patients with psoriasis ( Table 1 ) [ 137 , 138 , 160 , 161 ].…”

Section: Anti-tnf-α As a Treatment For Mood Disordersmentioning

confidence: 99%

Anti-TNF-α Compounds as a Treatment for Depression

Uzzan

Azab

2021

Molecules

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Millions of people around the world suffer from psychiatric illnesses, causing unbearable burden and immense distress to patients and their families. Accumulating evidence suggests that inflammation may contribute to the pathophysiology of psychiatric disorders such as major depression and bipolar disorder. Copious studies have consistently shown that patients with mood disorders have increased levels of plasma tumor necrosis factor (TNF)-α. Given these findings, selective anti-TNF-α compounds were tested as a potential therapeutic strategy for mood disorders. This mini-review summarizes the results of studies that examined the mood-modulating effects of anti-TNF-α drugs.

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Systemic TNF-α blockade attenuates anxiety and depressive-like behaviors in db/db mice through downregulation of inflammatory signaling in peripheral immune cells

Cited by 23 publications

References 70 publications

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice

Enhanced Anxiety and Olfactory Microglial Activation in Early-Stage Familial Alzheimer’s Disease Mouse Model

Anti-TNF-α Compounds as a Treatment for Depression

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