Novel insights into the mechanisms underlying depression-associated experimental autoimmune encephalomyelitis

Duarte-Silva, Eduardo; Macedo, Danielle; Maes, Michaël; Peixoto, Christina Alves

doi:10.1016/j.pnpbp.2019.03.001

Cited by 21 publications

(12 citation statements)

References 83 publications

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“…These differences may suggest that EAE behavioral symptoms, and more specifically depressive symptoms, are probably not associated with sickness behavior (Duarte-Silva et al, 2019). Similarly to depressed MS patients, depressive-like symptoms in EAE have been associated to increased TNF-α and IL-1β plasmatic levels, increased inflammatory activity mediated by CD4+ and CD8+ T-lymphocytes in both peripheral blood and CNS and inflammation-mediated hypothalamic release of CRH (Duarte-Silva et al, 2019). EAE exhibits a depressive behavioral phenotype linked also to increased levels of IL-1β and TNF-α in the brain.…”

Section: Cytokine Hypothesis In Ms Depressionmentioning

confidence: 97%

“…Differently from sickness behavior, EAE behavioral symptoms are associated to a chronic activation of HPA axis, increased inflammatory activity together with synaptic alterations (Duarte-Silva et al, 2019). These differences may suggest that EAE behavioral symptoms, and more specifically depressive symptoms, are probably not associated with sickness behavior (Duarte-Silva et al, 2019). Similarly to depressed MS patients, depressive-like symptoms in EAE have been associated to increased TNF-α and IL-1β plasmatic levels, increased inflammatory activity mediated by CD4+ and CD8+ T-lymphocytes in both peripheral blood and CNS and inflammation-mediated hypothalamic release of CRH (Duarte-Silva et al, 2019).…”

Section: Cytokine Hypothesis In Ms Depressionmentioning

confidence: 99%

“…Preclinical studies investigated the link between mood disturbances and cytokines (Il-1β and TNF-α) in EAE (Mandolesi et al, 2012;Gentile et al, 2015). Regarding EAE behavioral symptoms, it is still debated whether mood disturbances are due to chronic alterations of both immune system and CNS or to an acute response to active or passive immunization used to induce EAE, resembling the LPS induced sickness behavior (Duarte-Silva et al, 2019). Differently from sickness behavior, EAE behavioral symptoms are associated to a chronic activation of HPA axis, increased inflammatory activity together with synaptic alterations (Duarte-Silva et al, 2019).…”

Section: Cytokine Hypothesis In Ms Depressionmentioning

confidence: 99%

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Inflammation-Associated Synaptic Alterations as Shared Threads in Depression and Multiple Sclerosis

Bruno

Dolcetti

Rizzo

et al. 2020

Front. Cell. Neurosci.

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In the past years, several theories have been advanced to explain the pathogenesis of Major Depressive Disorder (MDD), a neuropsychiatric disease that causes disability in general population. Several theories have been proposed to define the MDD pathophysiology such as the classic “monoamine-theory” or the “glutamate hypothesis.” All these theories have been recently integrated by evidence highlighting inflammation as a pivotal player in developing depressive symptoms. Proinflammatory cytokines have been indeed claimed to contribute to stress-induced mood disturbances and to major depression, indicating a widespread role of classical mediators of inflammation in emotional control. Moreover, during systemic inflammatory diseases, peripherally released cytokines circulate in the blood, reach the brain and cause anxiety, anhedonia, social withdrawal, fatigue, and sleep disturbances. Accordingly, chronic inflammatory disorders, such as the inflammatory autoimmune disease multiple sclerosis (MS), have been associated to higher risk of MDD, in comparison with overall population. Importantly, in both MS patients and in its experimental mouse model, Experimental Autoimmune Encephalomyelitis (EAE), the notion that depressive symptoms are reactive epiphenomenon to the MS pathology has been recently challenged by the evidence of their early manifestation, even before the onset of the disease. Furthermore, in association to such mood disturbance, inflammatory-dependent synaptic dysfunctions in several areas of MS/EAE brain have been observed independently of brain lesions and demyelination. This evidence suggests that a fine interplay between the immune and nervous systems can have a huge impact on several neurological functions, including depressive symptoms, in different pathological conditions. The aim of the present review is to shed light on common traits between MDD and MS, by looking at inflammatory-dependent synaptic alterations associated with depression in both diseases.

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Section: Cytokine Hypothesis In Ms Depressionmentioning

confidence: 97%

Section: Cytokine Hypothesis In Ms Depressionmentioning

confidence: 99%

Section: Cytokine Hypothesis In Ms Depressionmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation-Associated Synaptic Alterations as Shared Threads in Depression and Multiple Sclerosis

Bruno

Dolcetti

Rizzo

et al. 2020

Front. Cell. Neurosci.

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“…Inflammatory cytokines have been proposed to regulate monoamine neurotransmitter metabolism by inhibiting neurotransmitter synthesis and promoting monoamine neurotransmitter hydrolysis ( 10 , 11 ). Therefore, inhibiting inflammation may be a potential therapeutic strategy for depression ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway

Wang

Guo

et al. 2020

Mol Med Rep

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asiaticoside is one of the triterpenoid components found in Centella asiatica that has promising neuroprotective properties. The present study aimed to evaluate the antidepressant-like properties of asiaticoside and to investigate the possible mechanisms underlying its mode of action using a mouse model of chronic unpredictable mild stress (cMS). Behavioral tests, including sucrose preference test, forced swimming test and tail suspension test, were performed to evaluate symptoms of depression. The expression levels of neurotransmitters, 5-hydroxytryptamine (5-HT) and norepinephrine (ne), in the hippocampus were measured by high-performance liquid chromatography. eliSa and western blotting were used to detect protein expression. it was demonstrated that asiaticoside treatment (20 and 40 mg/kg; intragastric) significantly reversed the decrease in sucrose consumption, and reduced the immobility time in tail suspension tests and forced swimming tests in cMS mice. Furthermore, asiaticoside treatment upregulated the expression of 5-HT and ne in the cMS mouse model. asiaticoside administration also downregulated the levels of interleukin (il)-1β, il-6 and tumor necrosis factor-α in the hippocampus, and reduced the phosphorylation of nuclear factor (nF)-κBp65 and the expression of nod-like receptor protein 3 (nlrP3), thus decreasing the expression of mature caspase-1. Furthermore, asiaticoside significantly increased the levels of cAMP and protein kinase a (PKa), and enhanced phosphorylation of the cAMP-related specific marker vasodilator-stimulated phosphoprotein at serine 157. Therefore, asiaticoside may activate the caMP/PKa signaling pathway to inhibit nF-κB-and NLRP3-related inflammation. Moreover, phosphorylation of the caMP-responsive element-binding protein at serine 133 and the expression of brain-derived neurotrophic factor were increased after asiaticoside administration. collectively, the present results suggested that asiaticoside may play a vital role as an antidepressant and anti-inflammatory agent in the CMS mouse model by regulating the caMP/PKa signaling pathway.

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“…EAE is the most commonly used experimental model for multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms [32] leads to an approximation of the key pathological features of MS: inflammation [33], demyelination [34], axonal loss, and gliosis. The most common EAE model is induced by myelin oligodendrocyte glycoprotein peptide 35–55 (MOG 35–55 ) [35, 36]; however, B cells are not effectively activated in MOG 35–55 EAE [35].…”

Section: Introductionmentioning

confidence: 99%

Treatment of the bone marrow stromal stem cell supernatant by nasal administration—a new approach to EAE therapy

et al. 2019

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IntroductionMultiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). CNS has its own unique structural and functional features, while the lack of precision regulatory element with high specificity as therapeutic targets makes the development of disease treatment in the bottleneck. Recently, the immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). However, the administration route and the safety evaluation limit the application of BMSC. In this study, we investigated the therapeutic effect of BMSC supernatant by nasal administration.MethodsIn the basis of the establishment of the EAE model, the BMSC supernatant were treated by nasal administration. The clinical score and weight were used to determine the therapeutic effect. The demyelination of the spinal cord was detected by LFB staining. ELISA was used to detect the expression of inflammatory factors in serum of peripheral blood. Flow cytometry was performed to detect pro-inflammatory cells in the spleen and draining lymph nodes.ResultsBMSC supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors. As a new, non-invasive treatment, there are no differences in the therapeutic effects between BMSC supernatant treated by nasal route and the conventional applications, i.e. intraperitoneal or intravenous injection.ConclusionsBMSC supernatant administered via the nasal cavity provide new sights and new ways for the EAE therapy.

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Novel insights into the mechanisms underlying depression-associated experimental autoimmune encephalomyelitis

Cited by 21 publications

References 83 publications

Inflammation-Associated Synaptic Alterations as Shared Threads in Depression and Multiple Sclerosis

Inflammation-Associated Synaptic Alterations as Shared Threads in Depression and Multiple Sclerosis

Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway

Treatment of the bone marrow stromal stem cell supernatant by nasal administration—a new approach to EAE therapy

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