Metformin Therapy Attenuates Pro-inflammatory Microglia by Inhibiting NF-κB in Cuprizone Demyelinating Mouse Model of Multiple Sclerosis

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model

“…Moreover, temporal regulation of microglia and macrophage activation is critical for efficient de- and remyelination ( Lampron et al., 2015 ; Miron et al., 2013 ). In a cuprizone mouse model, the levels of iNOS, TNF-α, and TSPO, which are expressed in pro-inflammatory microglia/macrophages, increase by weeks 5–6 of cuprizone treatment, whereas the levels of CD206, CD163, and Arg1, which are expressed in alternate microglia/macrophages, do not significantly change during or after cuprizone treatment ( Abdi et al, 2021 ; Klein et al., 2018 ). We therefore focused our analysis on CD16/32, which is expressed in pro-inflammatory microglia and macrophages ( de Almeida et al., 2020 ; Miron et al., 2013 ).…”

Microglia/macrophage polarization regulates spontaneous remyelination in intermittent cuprizone model of demyelination

“…In this regard, it is reported that 17b-estradiol and medroxyprogesterone acetate can alter microglial polarity through reduction of NLRP3 inflammasome [ 30 , 31 ]. In addition, methylprednisolone acetate and metformin can switch microglia/macrophage from M1 to M2 polarity [ 32 , 33 ]. In our study, intermittent demyelination resulted in alteration in microglia/macrophage phenotype, so that, CD86 and iNOS genes as the markers of M1 polarity were increased in the CPZ group while MRC-1 and TREM-2, which are related to M2 polarity, decreased in this group.…”

Microglial inflammation modulates opioid analgesic tolerance

“…Moreover, studies have shown that metformin is capable of attenuating NF-κB activation in microglia (Abdi et al, 2021), a process that enables the transcription of different proinflammatory molecules in different cell types including microglia (Shabab et al, 2017), indicating an important mechanism by which metformin can control microglia-mediated inflammation.…”

“…It has been revealed that systemic administration of metformin suppresses morphine‐induced activation of microglia in the spinal cord to attenuate the development of chronic morphine tolerance in mice (Pan et al, 2016). Moreover, studies have shown that metformin is capable of attenuating NF‐κB activation in microglia (Abdi et al, 2021), a process that enables the transcription of different proinflammatory molecules in different cell types including microglia (Shabab et al, 2017), indicating an important mechanism by which metformin can control microglia‐mediated inflammation. Minocycline: It is a second‐generation tetracycline, known to inhibit the production of proinflammatory molecules from activated microglia via suppression of NF‐κB activation (Kobayashi et al, 2013). In addition, minocycline treatment also blocks the effects of proinflammatory chemokine CCL2 on dorsal root‐evoked currents in spinal cord slices induced by MOR agonist [D‐Ala 2 , N‐Me‐Phe 4 , Gly 5 ‐ol]‐enkephalin (DAMGO) (Heles et al, 2021).…”