The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity

Taene, Abdolghader; Khalili-Tanha, Ghazaleh; Esmaeili, Aliakbar; Mobasheri, Leila; Kooshkaki, Omid; Jafari, Somaieh; Shokouhifar, Alireza; Sarab, Gholamreza Anani

doi:10.1007/s12031-019-01401-0

Cited by 38 publications

(34 citation statements)

References 24 publications

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“…To date, we identified seven articles investigated NLRP3 inflammasome activation in neuropsychiatric patients suffering from mood disorders, including major depressive disorder (MDD) and bipolar disorder [24][25][26][27][28][29][30]. Across studies investigating these mood disorders, the techniques used to measure the NLRP3 inflammasome were real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme linked immunosorbent (ELISA), and Western blotting (Table 1).…”

Section: Overview Demonstrates the Relevance Of Nlrp3 Inflammasome In Mood Disordersmentioning

confidence: 99%

Characterizing the NLRP3 Inflammasome in Mood Disorders: Overview, Technical Development, and Measures of Peripheral Activation in Adolescent Patients

Zhou

Fernando

Pan

et al. 2021

IJMS

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The NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome is a node of intracellular stress pathways and a druggable target which integrates mitochondrial stress and inflammatory cascades. While a body of evidence suggests the involvement of the NLRP3 inflammasome in numerous diseases, a lack of reliable measurement techniques highlights the need for a robust assay using small quantities of biological samples. We present a literature overview on peripheral activation of the NLRP3 inflammasome in mood disorders, then outline a process to develop and validate a robust assay to measure baseline and activated intracellular levels of “apoptosis-associated speck-like protein containing a CARD” (ASC) as a key component of an inflammatory profile in peripheral blood mononuclear cells (PBMC). A consistent association between high NLRP3 mRNA levels and relevant cytokines was seen in the literature. Using our method to measure ASC, stimulation of PBMC with lipopolysaccharide and nigericin or adenosine triphosphate resulted in microscopic identification of intracellular ASC specks, as well as interleukin 1 (IL-1) beta and caspase-1 p10 in the periphery. This was abolished by dose-dependent pre-treatment with 100 nM MCC950. We also report the use of this technique in a small pilot sample from patients with bipolar disorder and depressive disorders. The results show that levels of intracellular ASC and IL-1 beta are sensitive to change upon activation and maintained over time, which may be used to improve the detection of NLRP3 activation and guide personalized therapeutic strategy in the treatment of patients.

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Section: Overview Demonstrates the Relevance Of Nlrp3 Inflammasome In Mood Disordersmentioning

confidence: 99%

Characterizing the NLRP3 Inflammasome in Mood Disorders: Overview, Technical Development, and Measures of Peripheral Activation in Adolescent Patients

Zhou

Fernando

Pan

et al. 2021

IJMS

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“…Compared to control, the NLRP3null mice had a reduced expression level and activation of IL-1β, indicating that NLRP3 plays a crucial role in the release of cytokines following stress stimuli [19]. Furthermore, this study suggests that the elevation of inflammasome activity as a result of stress is crucial in development of major depressive symptoms [11]. This study therefore suggests that stress and NLRP3 may be contributors to MDD pathology.…”

Section: Cytokinementioning

confidence: 69%

“…The studies determined that depressed individuals showed elevated levels of cytokines, specifically TNF-ɑ [10]. A study by Taene et al demonstrated that increased stress levels, and thus elevated NLRP3 inflammasome activity, increases the development of depressive symptoms [11]. These studies therefore supported the connection between the concentration of cytokines and MDD symptoms.…”

Section: Resultsmentioning

confidence: 90%

“…Anhedonia, the reduced ability to feel pleasure or motivation and a common symptom of MDD, has been shown to be as a result of a downregulation of the dopaminergic system [5]. Research on rodents has shown that dopamine is associated with reward anticipation and impacts motivation levels [11]. These findings implicate dopamine as an important player in contributing to depressive symptoms.…”

Section: Monoaminementioning

confidence: 99%

“…Upon the detection of stress, glial cells respond by releasing cytokines, playing an important role in the CNS immune response [17][18]. Inflammatorybased immune response and the detection of signals such as stress, is controlled by the nod-like receptor protein 3 (NLRP3), which releases cytokines upon stress detection [11]. In a study by Zhang et al, NLRP3-null mice were subjected to mild stress for 4 weeks, including cage tilting/shaking, damp bedding and exposure to cold water for several hours [19].…”

Section: Cytokinementioning

confidence: 99%

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What are the Recurring Theories Regarding the Pathogenesis of Major Depressive Disorder?

Alawie

McLeod

2021

URNCST Journal

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Introduction: Several theories regarding the etiology of Major Depressive Disorder (MDD) provoke challenges in defining the exact pathology of the disorder. Among these theories, the most recurring theories were the monoamine hypothesis, cytokine hypothesis, and endocrine factors. Each of these hypotheses are backed with neurobiological studies and provide unique insight on the etiology of MDD. The current state of the literature of MDD is confusing and complex. There are various theories that explain the pathogenesis of MDD, each supported with evidence from pre-clinical and clinical studies. In this review, we aim to explain the most common theories of MDD and identify connections to the pathological mechanisms of this disease. Methods: A literature search considering inclusion/exclusion criteria was conducted to determine the different theories on the pathology of MDD and their limitations. Results: Using the inclusion/exclusion criteria, 44 articles were analyzed to form the basis of our review. Three main theories were found to be the most recurring, the monoamine hypothesis, cytokine hypothesis, and endocrine factors. Discussion: The monoamine hypothesis suggests that MDD is due to a deficiency of monoamines, specifically the hormone 5-HT, or serotonin. In contrast, the cytokine hypothesis proposes that the abnormal regulation of proinflammatory cytokines is linked to MDD through multiple facets. Finally, dysfunction of the hypothalamic-pituitary-adrenal axis is currently being studied as several papers have reported increased cortisol levels in patients with MDD, suggesting a relation between the two. Conclusion: This paper investigates the recurring theories regarding the pathogenesis of Major Depressive Disorder. However, further analysis revealed that the theories contain several inconsistencies that weaken their respective arguments. This includes unanticipated latency of drug effects, contradictory reports, and failed replications. Many argue that these hypotheses are not the cause of Major Depressive Disorder, but rather a concomitant occurrence. Major Depressive Disorder includes diverse symptoms with various external causes, a matter which makes it difficult to accurately define its pathology. Advanced neurobiological research enables easier diagnosis and the development of effective treatments used by clinicians. Consequently, it is imperative to have a thorough understanding of the pathologic process.

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Acupuncture inhibits NLRP3 inflammasome activation in the prefrontal cortex of a chronic stress rat model of depression

Wang

et al. 2021

The Anatomical Record

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The Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomedriven inflammatory response plays a key role in the pathophysiology of depression. Mounting evidence suggests that acupuncture is an effective treatment for depression. In this study, we investigated the effects of acupuncture treatment at the acupoints Baihui (GV20) and Yintang (GV29) on NLRP3 inflammasome in the prefrontal cortex (PFC) of an animal model of depression. Rats that underwent chronic unpredictable mild stress (CUMS) for 6 weeks showed depressivelike behaviors, which were confirmed by sucrose preference and locomotor activity in the open field test. The protein levels of NLRP3, apoptotic speckcontaining protein with a card (ASC), and cysteinyl aspartate specific proteinase-1 (Caspase-1) in the PFC were detected by Western blot analysis. The mRNA and protein expressions of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the PFC were measured by the real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that the depressive-like behaviors in stressed rats were reversed by acupuncture treatment. Compared with control rats, the protein expression of NLRP3, ASC, and Caspase-1 and the mRNA and protein expressions of IL-1β and IL-18 in the PFC were markedly increased in CUMS rats. Acupuncture treatment significantly decreased the levels of NLRP3 inflammasome components and inflammatory cytokines in the PFC. Acupuncture treatment also reduced the number of TUNEL-positive cells in the PFC. These results suggested that acupuncture has antidepressant-like effects, and its mechanism appears to be involved in the inhibition of NLRP3 inflammasome activation and apoptosis in the PFC.

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The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity

Cited by 38 publications

References 24 publications

Characterizing the NLRP3 Inflammasome in Mood Disorders: Overview, Technical Development, and Measures of Peripheral Activation in Adolescent Patients

Characterizing the NLRP3 Inflammasome in Mood Disorders: Overview, Technical Development, and Measures of Peripheral Activation in Adolescent Patients

What are the Recurring Theories Regarding the Pathogenesis of Major Depressive Disorder?

Acupuncture inhibits NLRP3 inflammasome activation in the prefrontal cortex of a chronic stress rat model of depression

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