Inhibition of Noncanonical Ca2+ Oscillation/Calcineurin/GSK-3β Pathway Contributes to Anti-Inflammatory Effect of Sigma-1 Receptor Activation

Gao, Tianyu; Gao, Ce; Liu, Zhidong; Wang, Yun; Jia, Xiaoxia; Tian, Hao; Lü, Qian; Guo, Lin

doi:10.1007/s11064-021-03439-2

Cited by 5 publications

(12 citation statements)

References 39 publications

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“…The whole operating process was referred to our published study. 25 In this study, the dilution of anti-total-GSK-3β antibody was 1:1,000, anti-p-GSK-3β, 1:800, and anti-GAPDH-, 1:3,000. The membranes were visualized using the Odyssey Infrared Imaging System (Odyssey SA, USA), and the band density was quantified using ImageJ software (National Institutes of Health, USA, Version 1.8).…”

Section: ■ Materials and Methodsmentioning

confidence: 82%

“…Recently, we identified a non-canonical inflammatory pathway in microglia, namely, the calcineurin/GSK-3β pathway. 25 Calcineurin dephosphorylates the phosphorylated GSK-3β and activates GSK-3β in LPS-activated microglia. PRE-084, a typical sigma-1 receptor agonist, inhibits the LPS-induced activation of microglia via inhibiting this non-canonical pathway.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The whole operating process was referred to our published study . In this study, the dilution of anti-total-GSK-3β antibody was 1:1,000, anti- p -GSK-3β, 1:800, and anti-GAPDH-, 1:3,000.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…The calcineurin activity was assayed using a colorimetric assay kit according to the manufacturer’s instruction. The operating process was referred to our published study . The calcineurin activity was defined as the produced amount of free phosphate in 1 mg protein per hour.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…The operating process was referred to our published study. 25 The calcineurin activity was defined as the produced amount of free phosphate in 1 mg protein per hour.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

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SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

Guo

Gao

Jia

et al. 2022

ACS Chem. Neurosci.

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Memory impairment and emotional disorder are two common clinical comorbidities in patients with epilepsy. It is imperative to develop a novel therapeutic agent or a strategy. 6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is a dopamine-1 receptor agonist and sigma-1 receptor allosteric modulator, which displays the neuron-protective and anti-neuroinflammation activity. We examined the effect of SKF83959 on the memory impairment and emotional disorder in the latent period of epilepsy using the mice post-status epilepticus model. We found that SKF83959 ameliorated memory impairment and depressive-like mood, alleviated the neuron damage and the formation of gliosis in hippocampus, suppressed the rise of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, and induced nitric oxide synthase in the latent period of epilepsy. Additionally, SKF83959 significantly inhibited the activity of calcineurin and glycogen synthase kinase-3β. All of these protective actions were reversed by BD1047 (a sigma-1 receptor antagonist). In addition, the intra-hippocampus injection of ketoconazole (a dehydroepiandrosterone synthesis inhibitor) also reversed the protective activity of SKF83959. Thus, we concluded that SKF83959 ameliorated the memory impairment and depressive-like mood in epilepsy via allosterically activating the sigma-1 receptor and subsequently inhibiting the calcineurin/glycogen synthase kinase-3β pathway.

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Section: ■ Materials and Methodsmentioning

confidence: 82%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Materials and Methodsmentioning

confidence: 99%

Section: Materials and Methodsmentioning

confidence: 99%

“…The operating process was referred to our published study. 25 The calcineurin activity was defined as the produced amount of free phosphate in 1 mg protein per hour.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

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SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

Guo

Gao

Jia

et al. 2022

ACS Chem. Neurosci.

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The sigma‐1 receptor‐TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis

Ji,

Gao,

Wang

et al. 2023

Anim Models and Exp Med

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BackgroundTherapy in the latent period is favorable for retarding the process of epileptogenesis. Recently, we have discovered that the activated sigma‐1 receptor (Sig‐1R) attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis. But the molecular mechanism needs further investigation.MethodsPRE‐084 was utilized as a research tool to highly selectively activate Sig‐1R in epileptic mice. After the treatment of PRE‐084, the pro‐inflammatory cytokines, neuropathological traits, and the level of mitochondrial translocator assembly and maintenance 41 homolog (TAMM41) in the hippocampus were examined. The mode in which the Sig‐1R interacts with TAMM41 was explored. The role of TAMM41 in the protecting effect of PRE‐084 was established.ResultsPRE‐084 inhibited the growth of pro‐inflammatory cytokines, reduced the formation of gliosis, alleviated neuronal damage in the hippocampus, and attenuated memory impairment in the latent period of epileptogenesis. The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE‐084‐treated mice. The Sig‐1R bound with TAMM41 directly, maintaining the stability of TAMM41. Knockdown of TAMM41 reversed the protective effect of PRE‐084, and overexpression of TAMM41 exhibited a similar protective action to that of PRE‐084.ConclusionWe presented the concept of the “sigma‐1 receptor–TAMM41 axis” and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.

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A Sigma₁ Receptor Agonist Alters Fluidity and Stability of Lipid Monolayers

Nakahara,

Hiranita,

Shibata

2024

Langmuir

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Interactions between the sigma 1 receptor agonist PRE-084 and various lipid monolayers, including dipalmitoylphosphatidylcholine (DPPC), DPP-ethanolamine (DPPE), DPP-glycerol (DPPG), DPP-serine (DPPS), palmitoylsphingomyelin (PSM), and cholesterol (Ch), were investigated to elucidate the effects of PRE-084 on membrane fluidity and stability. Their interactions with sigma 1 receptor agonists have potential implications for neuroprotection, antidepressant, analgesic, and cognitive enhancement effects. In this study, we observed that the presence of PRE-084 in the subphase led to increased fluidity in DPPC and DPPE monolayers, whereas decreasing fluidity was observed in DPPG, DPPS, and PSM monolayers. The interaction of PRE-084 with Ch monolayers was found to be distinct from its interaction with other lipids. Fluorescence microscopy images revealed changes in the size and shape of liquid-condensed domains in the presence of PRE-084, supporting the notion of altered membrane fluidity. Our findings provide new insights into the interaction of PRE-084 with lipid monolayers and its potential implications for biological and membrane science.

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Inhibition of Noncanonical Ca2+ Oscillation/Calcineurin/GSK-3β Pathway Contributes to Anti-Inflammatory Effect of Sigma-1 Receptor Activation

Cited by 5 publications

References 39 publications

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

The sigma‐1 receptor‐TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis

A Sigma₁ Receptor Agonist Alters Fluidity and Stability of Lipid Monolayers

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Inhibition of Noncanonical Ca2+ Oscillation/Calcineurin/GSK-3β Pathway Contributes to Anti-Inflammatory Effect of Sigma-1 Receptor Activation

Cited by 5 publications

References 39 publications

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

The sigma‐1 receptor‐TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis

A Sigma1 Receptor Agonist Alters Fluidity and Stability of Lipid Monolayers

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A Sigma₁ Receptor Agonist Alters Fluidity and Stability of Lipid Monolayers