Minocycline Promotes BDNF Expression of N2a Cells via Inhibition of miR-155-Mediated Repression After Oxygen-Glucose Deprivation and Reoxygenation

Abstract

Minocycline, an anti-infective agent of a tetracycline derivative, is reported to improve behavioral functional recovery after cerebral ischemia via enhancing the levels of brain-derived neurotrophic factor (BDNF). However, the precise mechanisms that minocycline targets to enhance the expression of BDNF are not fully defined. In the present study, we observed the neuroprotective effect and its potential mechanisms of minocycline using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N2a cells. We found that 50 µM minocycline protected against neuronal apoptosis induced by OGD/R injury, with increased expression ratio of Bcl-2/Bax and reduced expression of caspase-3. Interestingly, minocycline resulted in the up-regulation of only BDNF protein, not BDNF mRNA in N2a cells treated with OGD/R. Furthermore, we found that minocycline inhibited OGD/R-induced up-regulation of miR-155 targeted BDNF transcripts. Moreover, miR-155 mimic could partially abolish the neuroprotective effects of minocycline via inhibiting the levels of BDNF protein. These findings suggest that minocycline is neuroprotective against ischemic brain injury through their modulation of miR-155-mediated BDNF repression.

Minocycline promotes functional recovery in ischemic stroke by modulating microglia polarization through STAT1/STAT6 pathways

“…Quantitative real-time polymerase chain reaction (qRT-PCR) was performed as previously described [24].…”

Demonstration by Infra-Red Imaging of a Temperature Control Defect in a Decompression Sickness Model Testing Minocycline

“…Minocycline inhibits caspase 1 (the proIL-1β-converting enzyme) (Sanchez Mejia et al, 2001), reduces cyclooxygenase-2 expression, prostaglandin E2 production (Yrjanheikki et al, 1999) and inducible nitric oxide synthase up-regulation (Yrjanheikki et al, 1998). Its use therefore inhibits immunological pathways including decreases in interleukin-1β and TNF-α (Afshari et al, 2018; Aparicio et al, 2018), or an increased expression ratio of Bcl-2/Bax and reduced expression of caspase-3 by the modulation of miR-155-mediated BDNF repression (Lu et al, 2018), an inflammatory and immune response regulator (Song and Lee, 2015). It was also suggested that it decreases the levels of toll-like receptor 2 (TLR2) content, and its adapter protein MyD88, as well as the levels of the protein NLRP3, which is indispensable in the composition of inflammasome (Garcez et al, 2018).…”

Applications of Acupuncture Therapy in Modulating the Plasticity of Neurodegenerative Disease and Depression: Do MicroRNA and Neurotrophin BDNF Shed Light on the Underlying Mechanism?

“…Other miRNAs are also potentially associated with stroke. For instance, miR-124, miR-210, miR-10b-5p, and miR-155 were shown to directly target BDNF [ 27 , 28 , 30 , 31 ]. Numerous studies have reported that the expression levels of BDNF in rat brain tissue surrounding the haematoma, the cerebral cortex, the peri-infract cortex, the subventricular zone, the striatum, the hippocampus, etc.…”

“…Similarly, in MCAO brain tissues, bioinformatic analysis showed that miR-10b-5p could bind directly to the 3′-UTR sites of BDNF and negatively regulate its expression [ 30 ]. In a recent study, miR-155 targeted BDNF, and downregulation of miR-155-targeted BDNF transcripts protected against ischaemic brain injury [ 31 ]. Another study reported a similar conclusion: miR-155, miR-1, miR-10b, and miR-191 directly repressed BDNF by binding to their predicted sites in the 3′-UTR of BDNF [ 32 ].…”