mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Garro-Martínez, Emilio; Fullana, M. Neus; Florensa-Zanuy, Eva; Senserrich, Júlia; Paz, Verónica; Ruiz‐Bronchal, Esther; Adell, Albert; Castro, Elena; Díaz, Álvaro; Pazos, Ángel; Bortolozzi, Analı́a; Pilar-Cuéllar, Fuencisla

doi:10.3390/ijms22168671

Cited by 23 publications

(13 citation statements)

References 90 publications

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“…We indeed observed that the hippocampal HO-1/CO system is involved in the depressive-like state of the animals, and CO-RM-3 administration can reverse the depressive-like symptoms. CO is known for its neuroprotective effects in the cortical amygdala and hippocampal neurons ( Hettiarachchi et al, 2014 ; Wang et al, 2017 ; Riego et al, 2018 ); the brain regions are involved in depression ( Sheline et al, 2002 ; Whalen et al, 2002 ; Liu et al, 2017b ; Seo et al, 2017 ; Du Preez et al, 2021 ; Garro-Martinez et al, 2021 ; Li et al, 2021 ; Ouyang et al, 2021 ; Qin et al, 2021 ; Sindermann et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects

et al. 2021

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Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety.

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Section: Discussionmentioning

confidence: 99%

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects

et al. 2021

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“…Therefore, to overcome this limitation, it is desirable that further studies are performed on suitable animal models. Moreover, it would be interesting to evaluate the effect of irisin administration on the mammalian target of the rapamycin (mTOR)-signaling pathway that plays a key role in the preclinical tests of novel antidepressant drugs [ 67 ]. Finally, further studies on aged animal models will be needed to focus on the interplay among MDD, dementia, and neurodegenerative diseases, as depression is not only the most frequent noncognitive disorder associated with cognitive deficits but also a risk factor that contributes to worsening the neurodegeneration [ 68 ].…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Antidepressant Effect of Intermittent Long-Term Systemic Administration of Irisin in Mice

Pignataro

Dicarlo

Zerlotin

et al. 2022

IJMS

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Depression is a psychiatric disorder increasingly diffused worldwide. Evidence suggests that irisin, a myokine secreted by contracting muscle, mediates beneficial effects on several targets, including the brain. Here, the potential antidepressant properties of long-term intermittent systemic irisin administration (100 µg/kg/weekly for 1 month) were evaluated in mice by the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Furthermore, to deepen the molecular pathways underlying irisin treatment, the expression of irisin precursor, neurotrophic/growth factors, and cytokines was analyzed. Irisin treatment significantly decreased the immobility time in the TST and FST, suggesting an antidepressant effect. Additionally, irisin seemed to display an anxiolytic-like effect increasing the time spent in the OFT arena center. These findings were probably due to the modulation of endogenous brain factors as the gene expression of some neurotrophins, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1), was upregulated only in irisin-treated mouse brain. Moreover, irisin modulated the expression of some cytokines (IL-1β, IL-4, IL-6, and IL-10). To the best of our knowledge, this is the first study demonstrating that the irisin antidepressant effect may be observed even with a systemic administration in mice. This could pave the way toward intriguing preclinical research in humans.

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“…Developing animal models of human illnesses is a challenging task for translational research, but it is indispensable to understanding pathomechanism, searching for biomarkers, and engineering novel treatment [ 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 ]. Migraine research is no exception.…”

Section: Animal Models Of Neurogenic Inflammationmentioning

confidence: 99%

Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research

et al. 2021

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Migraine is a primary headache disorder characterized by a unilateral, throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors, and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses, including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This narrative review discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.

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mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Cited by 23 publications

References 90 publications

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects

Antidepressant Effect of Intermittent Long-Term Systemic Administration of Irisin in Mice

Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research

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