MicroRNAs Expression Mechanisms References
MicroRNA-15a Downregulation (pilocarpine, Mg2+ -free medium) MicroRNA-15a targets GFAP to inhibit inflammation and apoptosis of hippocampal neurons by downregulating GFAP in pilocarpine-induced epilepsy rat model and Mg2+-free medium treated TLE cell model. Propofol regulates microRNA-15a-5p/GluN2B/ERK1/2 pathway to suppress apoptosis hippocampal neuronal apoptosis in Mg2+ -free medium treated epilepsy cell model. (Fan et al., 2020; Liu et al., 2020)
MicroRNA-20a-5p
Upregulation (PTZ)
MicroRNA-20a-5p is involved in synaptic plasticity and silencing microRNA-20a-5p inhibits neuronal branching and axonal growth and prevents epileptogenesis by regulating RGMa-RhoA-mediated synaptic plasticity in the PTZ-induced epilepsy model.
(Feng et al., 2020)
MicroRNA-21-5p Upregulation (electrical kindling, KA, pilocarpine) MicroRNA-21-5p reduces IL-6 levels, loss of hippocampal neurons and apoptosis by inhibiting STAT3 expression, which suggesting protective effects of microRNA-21-5p in hippocampal neurons of epileptic rats. In KA-induced SE models, targeting of microRNA-21-5p also protects against seizure-induced injury by PTEN-mTOR. (Tang et al., 2018; Zhang et al., 2020)
MicroRNA-22 Downregulation (KA, pilocarpine) MicroRNA-22 inhibit neuroinflammatory signaling to protect against the development of epileptogenic brain networks. MicroRNA-22 prevents inflammation and development of epileptogenic focus by targeting P2X7R in the brain and microRNA-22 regulates aberrant neurogenesis and changes in neuronal morphology after SE in KA-induced epilepsy mice model. (Jimenez-Mateos et al., 2015; Beamer et al., 2018; Almeida Silva et al., 2020)
MicroRNA-23a Upregulation (KA, pilocarpine) MicroRNA-23a is involved in hippocampal neuron injury, hippocampal oxidative damage and impairment of spatial memory in KA-induced TLE mice. MicroRNA-23a can also regulate ADAM10, which contributes to epileptogenesis in pilocarpine-induced SE mice. (Zhu et al., 2019a; Zhu et al., 2019b)
MicroRNA-25-3p Downregulation (KA, Mg2+ -free medium) MicroRNA-25-3p targets OXSR1 to suppress oxidative stress and apoptosis of neurons, thereby suppressing epileptiform discharges in KA-induced epilepsy mice model and Mg2+ -free medium treated epilepsy cell model. (Li et al., 2020)
MicroRNA-27a-3p Upregulation (KA) MicroRNA-27a-3p regulates ion channel-related DEGs in multiple mTLE and downregulation of microRNA-27a-3p inhibits apoptosis of hippocampal neurons and inflammatory response by upregulating MAP2K4 in KA-induced epilepsy models. (Lu et al., 2019; Su et al., 2022b)
MicroRNA-29a Downregulation (Mg2+-free medium) MicroRNA-29a regulates seizure-induced cell death and inflammation in Mg2+-free medium treated epilepsy cell model. (Wu et al., 2021)
MicroRNA-34 Downregulation (KA, PTZ, Mg2+-free medium, epilepsy patients, TSC) Activated microRNA-34a may lead to impaired corticogenesis in TSC during early brain development and inhibition of microRNA-34a can regulate apoptosis and Notch signaling to inhibit epileptiform discharges in Mg2+-free medium treated epilepsy cell model. MicroRNA-34c plays a negative role in seizure and cognitive function by regulating NMDARs and AMPARs in PTZ-induced epilepsy rat model. Decreased microRNA-34c-5p enhances neuroinflammation to increase loss of hippocampal neuron in DRE from KA-induced epilepsy mice model and in children with DRE. (Huang et al., 2018; Wang et al., 2019a; Fu et al., 2020; Korotkov et al., 2021)
MicroRNA-101a-3p Downregulation (pilocarpine, Mg2+ -free medium) MicroRNA-101a-3p inhibits apoptosis and autophagy by downregulating c-FOS in pilocarpine-induced epilepsy rat model and Mg2+-free medium treated TLE cell model. (Geng et al., 2021)
MicroRNA-103a Upregulation (pilocarpine) Inhibition of microRNA-103a regulates BDNF to improve neuron injury and inhibit activated astrocytes in pilocarpine-induced epilepsy rat model. (Zheng et al., 2019)
MicroRNA-124 Downregulation (pilocarpine, PTZ) MicroRNA-124 inhibits some target genes to prevent upregulation of hippocampal NRSF, which participates in epilepsy and promotes the activation of hippocampal microglia and inflammatory cytokines. MicroRNA-124 suppresses seizure, regulates CREB1 activity, and inhibits neuronal firing with decreased expression of NMDAR in pilocarpine and PTZ-induced epilepsy rat model. (McClelland et al., 2014; Brennan et al., 2016; Wang et al., 2016c)
MicroRNA-125a-5p Downregulation (PTZ) MicroRNA-125a-5p targets CaMK4 to alleviate dysfunction and inflammation in PTZ-induced epilepsy rat model. (Liu et al., 2019b)
MicroRNA-128 Downregulation (epilepsy patients, glioma-associated epilepsy) / Upregulation (KA, pilocarpine) microRNA-128 is upregulated in KA-induced epilepsy rat model and promotes apoptosis by the SIRT1 cascade in PC12 cells. MicroRNA-128 can inhibit the expression of various ion channels and the signaling of ERK2 network that regulate neuronal excitability. MicroRNA-128 also inhibits SNAP-25 and SYT1 expression to regulate epilepsy sensitivity in KA-induced epilepsy mice model. (Tan et al., 2013; Alsharafi and Xiao, 2015; Chen et al., 2019; Wang et al., 2021b).
MicroRNA-129 Downregulation (KA, epilepsy patients) Inhibition of microRNA-129-2-3p regulates GABRA1 to protect against refractory TLE in KA-treated primary hippocampal neurons and KA-induced epilepsy rat model. MicroRNA-129-5p also targets HMGB1 to inhibit the development of autoimmune encephalomyelitis-related epilepsy by TLR4/NF-kB pathway. (Liu et al., 2017a; Wang et al., 2021a)
MicroRNA-132 Upregulation (KA, Mg2+-free medium) Depletion of microRNA-132 can reduce seizure-induced neuronal death in KA-induced epilepsy mice models and microRNA-132 can suppress BDNF/TrkB signaling to aggravate epileptiform discharges in the Mg2+-free treated hippocampal neuronal model of SE. MicroRNA-132 also reduces the expression of pro-epileptogenic factors (COX-2, IL-1β, TGF-β2, CCL2 and MMP3) in human cultured astrocytes of TLE. (Jimenez-Mateos et al., 2011; Xiang et al., 2015; Korotkov et al., 2020)
MicroRNA-134 Upregulation (KA, pilocarpine, Mg2+-free medium, epilepsy patients) Inhibition of microRNA-134 can effectively reduce the occurrence of spontaneous recurrent seizures and silencing microRNA-134 can produce neuroprotective, reducing the severity of seizures in KA-induced epilepsy mice model. MicroRNA-134 inhibits the expression of CREB and p-CREB to regulate synaptic plasticity in pilocarpine-induced epilepsy rat model. (Jimenez-Mateos et al., 2012; Zhu et al., 2015; Morris et al., 2019)
MicroRNA-135a Upregulation (KA, epilepsy patients) Antagonizing microRNA-135a can reduce spontaneous recurrent seizures to affect synaptic function and plasticity by targeting Mef2a in KA-induced epilepsy mice model. Inhibition of microRNA-135a protects glial cells against apoptosis by regulating SIRT1-related signaling pathway in KA-induced BV2 microglia epilepsy model. (Vangoor et al., 2019; Wang et al., 2021c)
MicroRNA-136 Downregulation (pilocarpine) MicroRNA-136 inhibits WNT/-Catenin signaling pathway to play a neuroprotective effect on pilocarpine-induced TLE rats. (Cui and Zhang, 2022)
MicroRNA-137 Downregulation (PTZ, pilocarpine, Mg2+-free medium) Overexpression of microRNA-137 inhibits seizure activity in two different epilepsy mouse models (PTZ and pilocarpine) and suppresses neuronal excitability in Mg2+-free-induced brain slice model of epileptiform activity. (Wang et al., 2018b)
MicroRNA-139-5P
Downregulation (pilocarpine, electrical kindling, epilepsy patients)
MicroRNA-139-5p negatively regulates GluN2A-NMDAR in pilocarpine-induced epilepsy rat model and TLE patients and upregulated microRNA-139-5p also regulates the Notch pathway to reduce spontaneous recurrent epileptiform discharge-induced apoptosis and oxidative stress in rat primary hippocampal neurons.
(Alsharafi et al., 2016; Zhao et al., 2021)
MicroRNA-141 Upregulation (KA) Inhibition of microRNA-141 can inhibit P53 to protect against apoptosis by SIRT1 expression in KA-induced epilepsy rat model. (Liu et al., 2019a)
MicroRNA-142 Upregulation (pilocarpine, epilepsy patients) MicroRNA-142 performs well in differentiating between drug-resistant and drug-sensitive TLE. Inhibition of microRNA-142 promotes mitochondrial autophagy and reduces hippocampal neuron damage by targeting PINK1 in pilocarpine-induced epilepsy rat model. (De Benedittis et al., 2021; Xiao et al., 2021)
MicroRNA-145 Upregulation (pilocarpine, epilepsy patients) Downregulation of microRNA-145 improves the abilities of learning and memory by reducing apoptosis of hippocampal neurons in pilocarpine-induced epilepsy rat model. (Zhao et al., 2019a)
MicroRNA-146a
Upregulation (KA, pilocarpine, epilepsy patients, TSC)
MicroRNA-146a is a powerful regulator of microglia-mediated inflammation in the chronic TLE. MicroRNA-146a-CFH-IL-1β loop circuit mediates the perpetuate inflammation of chronic TLE in KA-induced epilepsy rat model and antagonists targeting microRNA-146a can protect against SE by regulating NF-κB pathway in pilocarpine-induced epilepsy rat model. MicroRNA-146a can ameliorate dysregulation of the MMP/TIMP proteolytic system in TSC.
(Aronica et al., 2010; Su et al., 2016; Li et al., 2018c; Zhang et al., 2018a; Broekaart et al., 2020)
MicroRNA-148a-3p Upregulation (Mg2+ -free medium) FS-related microRNA-148a-3p plays neuroprotective roles by increasing the proliferation of hippocampal neurons in Mg2+ -free medium treated epilepsy cell model. (Yu et al., 2021)
MicroRNA-153 Downregulation (epilepsy patients) MicroRNA-153 is downregulated in plasma and temporal cortex of mTLE patients and overexpression of microRNA-153 reduces HIF-1α expression in rat astrocytes of refractory epilepsy. (Li et al., 2016)
MicroRNA-155
Upregulation (KA, pilocarpine)
MicroRNA-155 contributes to epileptogenesis through the PI3K/Akt/mTOR signaling pathway. Inhibition of microRNA-155 attenuates MMP3 expression in cultured human astrocytes, increases the expression of BDNF and alleviates seizure severity in the pilocarpine-induced epilepsy, and attenuates KA-induced seizure by inhibiting microglia activation.
(Cai et al., 2016; Duan et al., 2018; Korotkov et al., 2018; Fu et al., 2019)
MicroRNA-181
Upregulation (KA, pilocarpine)
MicroRNA-181b can inhibit P38/JNK signaling pathway by targeting TLR4, thereby reducing apoptosis and autophagy in KA-induced epilepsy rat model. Inhibition of microRNA-181a-5p also activates SIRT1 to reduce neuronal apoptosis, neuroinflammation, oxidative stress, cognitive dysfunction and activation of astrocyte and microglia in pilocarpine-induced epilepsy rat model.
(Wang et al., 2019b; Kong et al., 2020)
MicroRNA-183
Upregulation (pilocarpine)
Downregulated microRNA-183 results in an inactivation of JAK/STAT signaling pathway by targeting Foxp1 to promote neuron proliferation and inhibit apoptosis of hippocampal neurons, thereby attenuating hippocampal neuron injury in pilocarpine-induced epilepsy rat model.
(Feng et al., 2019)
McroiRNA-187-3p
Upregulation (electrical kindling)
MicroRNA-187-3p is upregulated and regulates KCNK10/TREK-2 potassium channel in electrical stimulation-induced SE.
(Haenisch et al., 2016)
MicroRNA-194-5p Upregulation (Mg2+ -free medium, epilepsy patients) MicroRNA-194-5p regulates the proliferation and apoptosis of hippocampus neuron in children with TLE and Mg2+ -free medium treated TLE cell model. (Niu et al., 2021)
MicroRNA-199a-5p
Upregulation (pilocarpine)
Targeting of microRNA-199a-5p protects against neuron damage by SIRT1-p53 cascade in pilocarpine-induced epilepsy rat model.
(Wang et al., 2016a)
MicroRNA-200c-3p
Upregulation (pilocarpine)
Downregulation of microRNA-200c-3p upregulates RECK and inactivates the AKT signaling to decrease apoptosis of hippocampal neuron in pilocarpine-induced epilepsy rat model.
(Du et al., 2019)
MicroRNA-203
Upregulation (KA, pilocarpine, epilepsy patients)
MicroRNA-203 is targeted to Ppp2ca in both humans and mice, which can target Ppp2ca to increase seizure activity in the KA-induced SE model. And microRNA-203 antagomirs can targets GLRB to decrease the frequency of spontaneous seizures in pilocarpine-induced mice epilepsy.
(Lee et al., 2017; Zhang et al., 2018b)
MicroRNA-204
Downregulation (Mg2+-free medium)
MicroRNA-204 regulates TrkB-ERK1/2-CREB signaling to inhibit epileptiform discharges in Mg2+-free medium cultured hippocampal neurons.
(Xiang et al., 2016)
MicroRNA-211 Downregulation Dynamic changes of microRNA-211 expression is associated with epileptiform activity and cholinergic imbalances in murine forebrain. (Bekenstein et al., 2017)
MicroRNA-219
Upregulation (KA, epilepsy patients)
MicroRNA-219 regulates NMDARs in the amygdala and hippocampus of patients with mTLE and also suppresses seizure formation by regulating the CaMKII/NMDAR pathway in KA-induced epilepsy mice model.
(Zheng et al., 2016; Hamamoto et al., 2020)
MicroRNA-221-3p
Downregulation (KA)
MicroRNA-221-3p inhibits HIF-1α to suppress seizures and microglia activation in the VPA-resistant epilepsy of KA-induced epilepsy mice model.
(Fu et al., 2021)
MicroRNA-223
Upregulation (KA, epilepsy patients)
MicroRNA-223 also have the good performance in distinguishing drug-sensitive and drug-resistant TLE and microRNA-223 affects microglial autophagy by targeting ATG16L1 in KA-induced epilepsy mice model.
(De Benedittis et al., 2021; He et al., 2021b)
MicroRNA-322-5p
Downregulation (pilocarpine)
MicroRNA-322-5p regulates the TLR4/TRAF6/NF-κB axis to reduce neuronal inflammation in pilocarpine-induced epilepsy rat model.
(Zhou et al., 2022)
MicroRNA-344a
Downregulation (PTZ)
MicroRNA-344a regulates seizure-induced apoptosis signaling pathways in PTZ-induced chronic epilepsy rat model.
(Liu et al., 2017b)
MicroRNA-451
Upregulation (KA)
MicroRNA-451 regulates GDNF expression to aggravate hippocampal neuronal apoptosis and seizure in KA-induced epilepsy mice model
(Weng et al., 2020)
MicroRNA-494
Downregulation (pilocarpine)
Overexpressed microRNA-494 inactivates the NF-κB signaling pathway to reduce hippocampal neuron injury by inhibiting RIPK1 in pilocarpine-induced epilepsy rat model.
(Qi et al., 2020)
MicroRNA-542-3p
Downregulation (KA)
MicroRNA-542-3p suppresses TLR4/NF-κB signaling pathway to reduce seizure-induced brain injury and the expression of P-gp in KA-treated primary hippocampal neurons and KA-induced epilepsy rat model.
(Yan et al., 2019)