Conquering depression

Kato, Takeshi; Kanba, Shigenobu

doi:10.1111/pcn.12257

Cited by 3 publications

(2 citation statements)

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“…The World Health Organization (WHO) estimates that over 264 million individuals worldwide suffer from major depressive disorder (MDD) [ 1 ], which is forecast to impose one of the greatest disease-related economic burdens by 2030 [ 2 ]. Current treatments for depression are not satisfactory, with sustained remission and appropriate disease management only being achieved in half of patients, while 20% of patients fail to respond at all to therapeutic intervention [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Qiu

Guo

Wang

et al. 2022

Bosn J of Basic Med Sci

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Major depressive disorder (MDD) is a highly pervasive, severe psychological condition for which the precise underlying pathophysiology is incompletely understood, although microglial activation is known to play a role in this context. In this study we analyzed the association between neuroinflammation and depressive-like behaviors in a lipopolysaccharide (LPS)-induced mouse model system using 10-12-week-old male C57BL/6 mice. Microglial activation and associated neuroinflammatory activity were monitored via positron emission tomography (PET) imaging. Animals were assessed at three time points, including 24 h prior to LPS injection, 24 h post-LPS injection, and 72 h post-LPS injection. Analyses of microglial activation and hippocampal neuroinflammation were conducted through [18]F DPA-714 PET imaging and immunohistochemical staining for ionized calcium-binding adapter molecule 1 (Iba-1) and translocator protein (TSPO). Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome activity and interleukin-1β (IL-1β) levels were assessed at 24 h post-LPS injection. We found that LPS treatment was associated with a marked increase in depressive-like behavior at 24 h post-injection time point, and that it was less pronounced at the 72 h post-injection time point. These changes coincided with enhanced [18F] DPA-714 PET uptake in the whole brain, hippocampus, cortex and amygdala together with increased hippocampal microglial activation as evidenced by immunofluorescent staining. By 72 h post-injection, however, these PET and immunofluorescence phenotypes had returned to baseline levels. Furthermore, increased NLRP3 inflammasome activation and IL-1β expression were evident at 24 h post-LPS injection. These data demonstrate that dynamic microglial activation is associated with LPS-induced depressive-like behaviors and hippocampal neuroinflammation in a mouse model system.

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Section: Introductionmentioning

confidence: 99%

Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Qiu

Guo

Wang

et al. 2022

Bosn J of Basic Med Sci

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“…Based on the statistical analysis from the World Health Organization, over 450 million people suffer from depression and it will rise to the top financial burden among all the diseases in 2030 ( Ustun et al, 2004 ; Smith 2014 ; Kato and Kanba, 2015 ). Typical clinical symptoms of depression include significant and long-term depressive mood, insensitivity, anhedonia and vital exhaustion ( Ellis et al, 2004 ; Szatmari et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Salidroside Improves Chronic Stress Induced Depressive Symptoms Through Microglial Activation Suppression

Yang

Chen

2021

Front. Pharmacol.

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Depression is a severe neurological disorder highly associated with chronic mental stress stimulation, which involves chronic inflammation and microglial activation in the central nervous system (CNS). Salidroside (SLDS) has been reported to exhibit anti-neuroinflammatory and protective properties on neurological diseases. However, the mechanism underlying the effect of SLDS on depressive symptoms has not been well elaborated. In the present study, the effects of SLDS on depressive behaviors and microglia activation in mice CNS were investigated. Behavioral tests, including Forced swimming test (FST), Open field test (OFT) and Morris water maze (MWM) revealed that SLDS treatment attenuated the depressive behaviors in stress mice. SLDS treatment significantly reduced the microglial immunoreactivity for both Iba-1 and CD68, characteristic of deleterious M1 phenotype in hippocampus of stress mice. Additionally, SLDS inhibited microglial activation involving the suppression of ERK1/2, P38 MAPK and p65 NF-κB activation and thus reduced the expression and release of neuroinflammatory cytokines in stress mice as well as in lipopolysaccharide (LPS)-induced primary microglia. Also, SLDS changed microglial morphology, attachment and reduced the phagocytic ability in LPS-induced primary microglia. The results demonstrated that SLDS treatment could improve the depressive symptoms caused by unpredictable chronic stress, indicating a potential therapeutic application of SLDS in depression treatment by interfering microglia-mediated neuroinflammation.

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