Neuroprotective effect of methyl lucidone against microglia-mediated neurotoxicity

Cui, Yanji; Wu, Jinji; Jung, Sung-Cherl; Kim, Gi-Ok; Ko, Ryeo Kyeong; Lee, Hye-Ja; Yoo, Eun-Sook; Kang, Hee‐Kyoung; Suk, Kyoungho; Eun, Su-Yong

doi:10.1016/j.ejphar.2012.05.041

Cited by 20 publications

(19 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To investigate the effects of LPS-stimulated BV2 microglia on PC12 cells, the PC12 cells were exposed to the microglia-conditioned media, according to a previously described protocol28. Cell viability was assessed using an MTT assay.…”

Section: Resultsmentioning

confidence: 99%

Interference with Protease-activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway

Yang

Quiñones‐Hinojosa

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Excessive microglial cells activation in response to inflammatory stimuli leads to synaptic loss, dysfunction, and neuronal cell death. Activated microglia are involved in the pathogenesis of neurological conditions and frequently contribute to several complications. Accumulating evidence suggests that signaling through PAR-1 is involved in inflammation, however, its function has yet to be fully elucidated. Here, we have demonstrated that the suppression of PAR-1 leads to down-regulation of inflammatory factors including IL-1β, IL-6, TNF-α, NO, as well as the prevention of activation of NF-κB in BV2 cells. In addition, we found that a PAR-1 antagonist, SCH, prevented LPS-induced excessive microglial activation in a dose-dependent manner. As a result of SCH treatment, neuronal cell death via up-regulation of Akt-mediated pathways was reduced. Our results demonstrate that the beneficial effects of SCH are linked to its ability to block an inflammatory response. Further, we found that SCH inhibited the death of PC12 neurons from the cytotoxicity of activated BV2 cells via activation of the PI3K/Akt pathway. These neuro-protective effects appear to be related to inhibition of PAR-1, and represents a novel neuroprotective strategy that could has potential for use in therapeutic interventions of neuroinflammatory disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Interference with Protease-activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway

Yang

Quiñones‐Hinojosa

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Systematic administration of minocycline has been shown to have an analgesic effect in various pain conditions . It is generally used as a selective glial inhibitor with no detectable direct effects on neurons .…”

Section: Discussionmentioning

confidence: 99%

Minocycline inhibits neurogenic inflammation by blocking the effects of tumor necrosis factor‐α

Gong

Zou

Fuchs

et al. 2015

Clin Exp Pharma Physio

View full text Add to dashboard Cite

It has been well established that neurogenic inflammation is one of the major pathological processes underlying inflammatory pain, but there are few effective anti-inflammatory drugs to alleviate such pain. The present study shows that minocycline, a widely used glial activation inhibitor, is effective in reducing neurogenic inflammation. Patch-clamp recordings showed that small sized dorsal root ganglion (DRG) neurons were dramatically excited following intradermal capsaicin injection in the rat hind paw, evidenced by decreased rheobase and membrane threshold. Pretreatment with minocycline (30 mg/kg for 1 day, intraperitoneal injection) blocked the increased neuronal excitability. Western blot and immunostaining of DRG revealed the activation of satellite glial cells (SGCs) following capsaicin injection. The up-regulation of glial fibrillary acidic protein (GFAP) was significantly inhibited by minocycline pre-administration. Measurement of tumor necrosis factor α (TNF-α) and its receptor, TNF-α receptor 1 (TNFR1), showed that minocycline mainly blocked the up-regulation of TNF-α in SGCs and TNFR1s in neurons following capsaicin injection. The pivotal role of TNF-α in neurogenic inflammation was further supported by the findings that incubation DRG with TNF-α mimicked the increased excitability of DRG neurons induced by capsaicin injection, and that TNF-α application enhanced cutaneous vasodilation in the hind paws induced by antidromic electrical stimulation of dorsal roots. Based on these results, we propose that minocycline is a potential therapeutic drug that can reduce neuronal excitability and neurogenic inflammation by working on SGCs to inhibit the expression of TNF-α.

show abstract

“…In healthy brain function, their immune ontogeny supports the likelihood that they are ardent phagocytes and cytokine producers. The fact that their ultimate resting place is juxtaneural suggests that they likely play key roles in neuronal maintenance and support; in the case of pathology, however, this intimate relationship with delicate neural cells allows microglia the ability to damage them via production of cytotoxic mediators [5–8]. Their infiltrative and expansive nature during embryogenesis indicates that they are motile cells, apt to respond to molecular gradients and proliferative signals.…”

Section: Origins Of Microgliamentioning

confidence: 99%

The role of microglia in brain maintenance: implications for Rett syndrome

Derecki

Cronk

Kipnis

2013

Trends in Immunology

View full text Add to dashboard Cite

The role of microglia in central nervous system pathology has been studied extensively, and more recently, examination of microglia in the healthy brain has yielded important insights into their many functions. It was long assumed that microglia were essentially “quiescent” cells, unless provoked into activation, which was considered a hallmark of disease. More recently, however, it has become increasingly clear that they are extraordinarily dynamic cells, constantly sampling their environment and adjusting to exquisitely delicate stimuli. Along these lines, our lab has identified a new and unexpected role for microglial phagocytosis—or lack thereof—in the pathophysiology of Rett syndrome, a neurodevelopmental disease caused by mutation of the gene encoding methyl-CpG binding protein (MECP)2. Namely, we showed that specific expression of wild-type Mecp2 in myeloid cells of Mecp2-null mice is sufficient to arrest major symptoms associated with this devastating disease. This beneficial effect, however, is abolished if phagocytic activity of microglia is inhibited. Here, we will discuss microglial origins, the role of microglia in brain development and maintenance, and the phenomenon of microglial augmentation by myeloid progenitor cells in the adult brain. Finally, we will address in some detail the beneficial roles of microglia as clinical targets in Rett syndrome and other neurological disorders.

show abstract

Neuroprotective effect of methyl lucidone against microglia-mediated neurotoxicity

Cited by 20 publications

References 31 publications

Interference with Protease-activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway

Interference with Protease-activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway

Minocycline inhibits neurogenic inflammation by blocking the effects of tumor necrosis factor‐α

The role of microglia in brain maintenance: implications for Rett syndrome

Contact Info

Product

Resources

About