miR-485 inhibits histone deacetylase HDAC5, HIF1α and PFKFB3 expression to alleviate epilepsy in cellular and rodent models

Abstract

We investigated the role of microRNA (miR)-485 and its downstream signaling molecules on mediating epilepsy in cellular and rat models. We established a cellular epilepsy model by exposing hippocampal neurons to magnesium and a rat model by treating ICR mice with lithium chloride (127 mg/kg) and pilocarpine (30 mg/kg). We confirmed that miR-485 could bind and inhibit histone deacetylase 5 (HDAC5) and then measured expression of miR-485 and in mice and cells. Cells were transfected with overexpression or knockdown of miR-485, HDAC5, hypoxia-inducible factor-1alpha (HIF1α), or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme (PFKFB3) to verify their roles in apoptosis, oxidative stress, and inflammation in epileptic hippocampal neurons. Binding relationship between miR-485, HDAC5, HIF1α, and PFKFB3 was verified. Oxidative stress and inflammation marker levels in epilepsy model mice were assessed. miR-485 was downregulated and HDAC5 was upregulated in cell and animal model of epilepsy. Seizure, neuronal apoptosis, oxidative stress (increased SOD and GSH-Px expression and decreased MDA and 8-OHdG expression) and inflammation (reduced IL-1β, TNF-α, and IL-6 expression) were reduced by miR-485 in epileptic cells. HIF1α and PFKFB3 expression was reduced by HDAC5 knockdown in cells, which was recapitulated in vivo . Thus, miR-485 alleviates neuronal damage and epilepsy by inhibiting HDAC5, HIF1α, and PFKFB3.

Semaglutide ameliorates lipopolysaccharide-induced acute lung injury through inhibiting HDAC5-mediated activation of NF-κB signaling pathway

“…To cite an instance, HDAC5 knockdown induced neuron apoptosis in an epilepsy model. 31 HDAC5 aggravated inflammation and cell apoptosis in acute pancreatitis. 32 Furthermore, HDAC5 activated the NF-κB pathway via Ghrelin and E2F1 inhibition, thereby exacerbating inflammatory response and apoptosis in LPS-challenged intestinal macrophages.…”

Altered miRNA Expression Profiles in the Serum of Beagle Dogs Experimentally Infected with Toxocara canis

“…The transcription level of miR-122 was not significantly different in dog livers infected with T. canis [16]; however, in this study, miR-122 was upregulated 5.69 times in the serum of Beagle dogs at 10 dpi, suggesting that miR-122 may have potential to act as a circulating biomarker in the serum of Beagle dogs at the middle stage of the T. canis infection. miR-485 participates in multiple biological processes, such as regulating antiviral immunity and restricting viral replication [33], inhibiting metastasis of lung adenocarcinoma by targeting Flot2 [34], and alleviating epilepsy in cellular and rodent models [35], suggesting that miR-485 plays a positive role in maintaining the body homeostasis, but this phenomenon does not seem to appear in the lung and liver of Beagle dogs infected with T. canis, where the expression of miR-485 was not significantly different [11,16]. However, it is worth noting that, in this study, the transcription level of miR-485 was downregulated 2.76 times in dog serum at 10 dpi.…”

Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus

“…Ion channel-related miRNAs include downregulated miR-324-5p (DG) [ 47 ]. Oxidative stress-related miRNAs include upregulated miR-221 (DG) [ 48 ] and downregulated miR-153 [ 49 ], miR-221 (CA) [ 50 ], and miR-485 [ 51 ]. P2X7 related miRNAs include upregulated miR-22 [ 52 ], and some unclassed miRNAs such as downregulated miR-145-5p (DG) [ 53 ], miR-204 (DG), and miR-218 [ 17 ].…”