Neuroprotective Effects of Viral Overexpression of microRNA-22 in Rat and Cell Models of Cerebral Ischemia-Reperfusion Injury

Abstract

Several studies have reported that microRNA (MIR) is involved in the pathogenesis and progression of ischemic diseases, including cerebral ischemia, and that MIR-22 may inhibit the inflammatory response and cell apoptosis, which contribute to ischemia/reperfusion (I/R) injury. However, the specific function of MIR-22 in cerebral I/R injury remains far from clear. This study aimed to examine the potential protective effect of MIR-22 against cerebral I/R injury and its mechanism. As predicted, adenovirus-mediated MIR-22 overexpression markedly reduced the neurological score and infarct size (P < 0.05). We demonstrated that MIR-22 overexpression resulted in a reduction in inflammatory cytokines TNF-α, IL-6, COX-2, and iNOS, whereas the level of IL-10 was enhanced. MIR-22 overexpression significantly inhibited NF-κB activity by decreasing NF-κB coactivator NCOA1 expression. Furthermore, we found that MIR-22 could reduce the apoptotic rate of cortical neurons. Caspase-3 activity was inhibited by MIR-22, and the expression of the anti-apoptosis gene Bcl-2 in neurons was increased and that of the pro-apoptosis gene Bax decreased following MIR-22 overexpression. Our results suggest that MIR-22 could be used to treat cerebral I/R injury and that its neuroprotective effect may be attributed to a reduction in inflammation and apoptosis.

MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1

“…Within the nervous system, the miR-22 family has been reported to participate in neuroprotection (Yu et al, 2015; Jovicic et al, 2013), neurodegeneration (Lee et al, 2011), neuroinflammation (Parisi et al, 2013; Siegel et al, 2012), neurodevelopment (Volvert et al, 2014; Berenguer et al, 2013), and neuroplasticity (Chen et al, 2013). Thus, although this family appears to have multiple roles in the nervous system and disease, our current studies identify members of this family as specifically involved in the suppression of memory formation.…”

Genetic deletion of microRNA-22 blunts the inflammatory transcriptional response to status epilepticus and exacerbates epilepsy in mice

“…The finding that loss of miR-22 results in an accelerated epileptogenesis suggests delivery or over-expression of miR-22 might be a potential therapeutic strategy. This could be achieved using miRNA mimics, synthetic double-stranded molecules or other approaches [17,18]. Notably, intracerebral injection of mimics for miR-22 and other inflammationlinked miRNAs has been reported to reduce seizures in the present model [16,36].…”

Over-Expression of MicroRNA-22 Protects Cardiomyocytes from Ischemic Injury

“…Another study found that after myocardial ischemia, over-expression of microRNA-1 can promote cardiomyocyte apoptosis, with the mechanism of inhibiting anti-apoptotic gene Bcl-2, IGF-1 expression and inducing cells into the process of apoptosis. Over-expression of microRNA-21 can reduce cell apoptosis, and its mechanism is to interfere with the activity of PDCD4 and AP-1, inhibit the ac- [19].…”