Amisulpride alleviates chronic mild stress-induced cognitive deficits: Role of prefrontal cortex microglia and Wnt/β-catenin pathway

Mohamed, Ahmed F.; Habib, Mohamed Z.; Ebeid, Mai A.; Abdelraouf, Sahar M.; Faramawy, Yasser el; Aboul‐Fotouh, Sawsan; Magdy, Yosra

doi:10.1016/j.ejphar.2020.173411

Cited by 24 publications

(14 citation statements)

References 70 publications

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“…The FST test results of the CMS rats are in accordance with many previous studies (Zhang et al , 2016; Mohamed et al , 2020; Fu et al , 2020). The decrease in the number of rearing caused by the CMS was also detected by Magara et al (2015).…”

Section: Discussionsupporting

confidence: 91%

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Pumpkin seed oil and zinc attenuate chronic mild stress perturbations in the cerebral cortex of rats

Elazma

El-Beih

El-Shamy

et al. 2022

NFS

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Purpose This study aims to investigate the potential of pumpkin seed oil (PSO) and zinc to attenuate oxidative stress and neuroinflammation caused by chronic mild stress (CMS) in the cerebral cortex of male rats. Design/methodology/approach The rats were submitted to stress for six weeks and then the behavior of the rats was tested by forced swimming test (FST) and novel cage test. The treated groups were given venlafaxine (20 mg/kg), pumpkin seed oil (40 mg/kg) and zinc (4 mg/kg). The cortex homogenate was used for the detection of the oxidative stress parameters, the concentration of neurotransmitters, tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), Na+/K+-ATPase activity, and the expression of histamine N-methyltransferase (Hnmt) and tyrosine hydroxylase (Th). Findings CMS causes a significant increase in immobility time in the FST and a significant decrease in the number of rearing in the novel cage test. CMS group showed a significant increase in alanine aminotransferase (ALT) activity, levels of cortisol, TNF-α, IL-1β, nitric oxide and malondialdehyde. CMS caused a significant decrease in the concentrations of serotonin, GABA, norepinephrine, and the activities of glutathione peroxidase, catalase, superoxide dismutase and Na+/K+-ATPase. CMS caused a marked reduction in the expression of Hnmt and Th in the cortex. PSO and zinc attenuated the Na+/K+-ATPase activity, oxidative parameters and neuroinflammation induced by the CMS, and this was reflected by the elevation of the concentration of neurotransmitters and reduction of cortisol and ALT, in addition to the behavior normalization. PSO and zinc attenuated the CMS by improving the antioxidant milieu and anti-inflammatory status of the cerebral cortex. Originality/value There are no studies on the effect of pumpkin seed oil on depression

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Section: Discussionsupporting

confidence: 91%

“…The attenuation by zinc or PSO was similar to what was reported after venlafaxine. The increase in cortisol levels during stress is also detected by Mohamed et al (2020). The elevation of cortisol in CMS rats is attributed to the activation of hypothalamus–pituitary–adrenal axis.…”

Section: Discussionmentioning

confidence: 91%

Pumpkin seed oil and zinc attenuate chronic mild stress perturbations in the cerebral cortex of rats

Elazma

El-Beih

El-Shamy

et al. 2022

NFS

View full text Add to dashboard Cite

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“…Abnormally activated microglias mediate neuroinflammatory response by producing a variety of proinflammatory factors, which is an important pathological process in CNS diseases [ 41 ]. Reducing the activation of microglia, thereby reducing the production of inflammatory factors and subsequent neuronal damage, offers potential treatment options for neuroinflammatory diseases [ 42 , 43 ]. IL-1 β has been implicated in a variety of CNS diseases, most of which are associated with inflammatory processes [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice

Song

Liang

Song

et al. 2022

Journal of Immunology Research

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Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5 ′ -monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors.

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“…When β-catenin levels in the NAc were inhibited using the non-selective β-catenin antagonist sulindac, it blocked the therapeutic-like effects of WIN55,212-2 on extinction [ 26 ]. The involvement of the Wnt/β-catenin pathway in antidepressant and pro-cognitive effects also has been observed in the medial prefrontal cortex (mPFC) [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Endocannabinoid Signaling via β-Catenin in the Nucleus Accumbens Attenuates PTSD- and Depression-like Behavior of Male Rats

et al. 2022

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Inhibition of fatty acid amide hydrolase (FAAH), which increases anandamide levels, has been suggested as a potential treatment for stress-related conditions. We examined whether the stress-preventing effects of the FAAH inhibitor URB597 on behavior are mediated via β-catenin in the nucleus accumbens (NAc). Male rats were exposed to the shock and reminders model of PTSD and then treated with URB597 (0.4 mg/kg; i.p.). They were tested for anxiety- (freezing, startle response), depression-like behaviors (despair, social preference, anhedonia), and memory function (T-maze, social recognition). We also tested the involvement of the CB1 receptor (CB1r), β-catenin, and metabotropic glutamate receptor subtype 5 (mGluR5) proteins. URB597 prevented the shock- and reminders-induced increase in anxiety- and depressive-like behaviors, as well as the impaired memory via the CB1r-dependent mechanism. In the NAc, viral-mediated β-catenin overexpression restored the behavior of rats exposed to stress and normalized the alterations in protein levels in the NAc and the prefrontal cortex. Importantly, when NAc β-catenin levels were downregulated by viral-mediated gene transfer, the therapeutic-like effects of URB597 were blocked. We suggest a potentially novel mechanism for the therapeutic-like effects of FAAH inhibition that is dependent on β-catenin activation in the NAc in a PTSD rat model.

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Amisulpride alleviates chronic mild stress-induced cognitive deficits: Role of prefrontal cortex microglia and Wnt/β-catenin pathway

Cited by 24 publications

References 70 publications

Pumpkin seed oil and zinc attenuate chronic mild stress perturbations in the cerebral cortex of rats

Pumpkin seed oil and zinc attenuate chronic mild stress perturbations in the cerebral cortex of rats

Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice

Enhancing Endocannabinoid Signaling via β-Catenin in the Nucleus Accumbens Attenuates PTSD- and Depression-like Behavior of Male Rats

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