Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function

Ghalibaf, Mohammad Hosein Eshaghi; Rajabian, Arezoo; Parviz, Mohsen; Akbarian, Mahsan; Amirahmadi, Sabiheh; Vafaee, Farzaneh; Hosseini, Mahmoud

doi:10.1016/j.heliyon.2023.e13452

Cited by 12 publications

(2 citation statements)

References 51 publications

(91 reference statements)

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“…Furthermore, the mechanism for the protective effect of surviving microglia that leads to good outcomes remains unknown. Following ischaemia/reperfusion or OGD/R in microglia, the production of free radicals leading to lipid peroxidation may overload the antioxidant defence system, which plays an important role in reversing the destructive effects of ROS [35][36]. However, whether the secretion of in ammatory factors from microglia or the cross-talk between microglia and neurons has an effect on the ferroptosis of microglia remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Minocycline alleviates microglial ferroptosis by inhibiting HO-1 during cerebral ischaemia reperfusion injury

Wang,

et al. 2024

Preprint

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Objective Ischaemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischaemia reperfusion injury (CIRI) usually leads to severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aimed to explore microglial death in CIRI and the effect and mechanism of minocycline treatment on microglia Methods A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h postoperation, 45 mg/kg minocycline was intraperitoneally injected into the rats. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, activated microglia and mitochondrial structure were observed and checked at 72 h after reperfusion. Moreover, an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with either various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and functioning, and labile Fe2+ and ferroptosis-associated gene/proteins levels were measured. Hemin was used for further validation after transcriptome analysis. Results In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglial ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe2+ levels, lipid peroxidation, and ferritin heavy chain (FTH) expression and improved mitochondrial structure and functioning in vitro. HO-1 overexpression counteracted the protective effect of minocycline. Conclusion Ferroptosis is a major form of microglial death in CIRI. The mechanism of the protective role of minocycline in CIRI is partly dependent on its ability to effectively ameliorate microglial ferroptosis by reducing HO-1 expression. Therefore, targeting microglial ferroptosis is a promising treatment for CIRI.

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Section: Discussionmentioning

confidence: 99%

Minocycline alleviates microglial ferroptosis by inhibiting HO-1 during cerebral ischaemia reperfusion injury

Wang,

et al. 2024

Preprint

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“…In brief, cortex homogenates were incubated with pyrogallol and MTT. The reaction was stopped by adding DMSO, and the absorbance was read at 420 nm (Eshaghi Ghalibaf et al, 2023).…”

Section: Biochemical Assessmentmentioning

confidence: 99%

Minocycline Mitigates Sepsis-Induced Neuroinflammation and Promotes Recovery in Mice: Insights into Neuroprotection and Inflammatory Modulation

Salmani,

Bardaghi,

Askarpour

et al. 2024

Preprint

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Aim: Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, particularly within the brain, was investigated in this study for its protective effects against sepsis-induced brain injury. Methods: Adult male C57 mice received pretreatment with varying doses of minocycline (12.5, 25, and 50 mg/kg) three days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Results: Septic mice exhibited significant weight loss and impaired spontaneous locomotor activity. Initially, minocycline did not attenuate the severity of weight loss (1 day) or locomotor activity impairment (4 hours post-sepsis), but it significantly accelerated the recovery of the mice in later days. Sepsis led to elevated mRNA expression of IL-1β and TNF-α, increased MDA levels, and decreased thiol content and SOD activity 24 hours after sepsis induction. Minocycline dose-dependently mitigated brain inflammation and oxidative stress damage. Conclusion: Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications.

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Minocycline alleviates microglia ferroptosis by inhibiting HO-1 during cerebral ischemia–reperfusion injury

Wang,

et al. 2024

Inflamm. Res.

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Objective Ischemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischemia–reperfusion injury (CIRI) typically results in severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aims to explore microglial death in CIRI and the effects and mechanism of minocycline treatment on microglia. Methods A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h post-operation, rats were intraperitoneally injected with 45 mg/kg minocycline. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, assessment of activated microglia and examination of mitochondrial structure were conducted and checked at 72 h after reperfusion. Additionally, an in vitro model of oxygen–glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and function, and labile Fe 2+ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis. Results In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglia ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe 2+ levels, lipid peroxidation, and expression of ferritin heavy chain (FTH) and it improved mitochondrial structure and function in vitro. Upregulation of HO-1 counteracted the protective effect of minocycline. Conclusion Ferroptosis is a major form of microglial death in CIRI. The protective mechanism of minocycline in CIRI partially hinges on its ability to effectively ameliorate microglia ferroptosis by downregulating HO-1 expression. Consequently, targeting microglia ferroptosis is a promising treatment for CIRI. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-024-01927-z.

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Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function

Cited by 12 publications

References 51 publications

Minocycline alleviates microglial ferroptosis by inhibiting HO-1 during cerebral ischaemia reperfusion injury

Minocycline alleviates microglial ferroptosis by inhibiting HO-1 during cerebral ischaemia reperfusion injury

Minocycline Mitigates Sepsis-Induced Neuroinflammation and Promotes Recovery in Mice: Insights into Neuroprotection and Inflammatory Modulation

Minocycline alleviates microglia ferroptosis by inhibiting HO-1 during cerebral ischemia–reperfusion injury

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