Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

Liu, Xijin; Yang, Zhiyong; Yin, Yaping; Deng, Xuejun

doi:10.4103/1673-5374.130083

Cited by 16 publications

(6 citation statements)

References 65 publications

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“…Notch signalling plays an important role in the neuroinflammation and neuronal damage in TLE [27]. Numerous studies have demonstrated that Notch signalling is activated in both TLE model rats and humans with TLE [18, 19]. Consistent with previous studies, we found that the expression of Notch-1 and its downstream target gene Hes-1 were significantly higher in the model group than in the control group.…”

Section: Discussionsupporting

confidence: 90%

“…It has been shown that Notch signalling is up-regulated in TLE mice and activation of Notch signalling further promotes the excitation of CA1 pyramidal neurons in acute seizures [18]. Notch-1 and hairy and enhancer of split 1 (Hes 1) are up-regulated in the temporal neocortex of patients with intractable TLE [19]. However, the regulatory mechanisms underlying the effects of miRNA-146a in Notch signalling remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1

et al. 2019

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This study aimed to evaluate the specific regulatory roles of microRNA-146a (miRNA-146a) in temporal lobe epilepsy (TLE) and explore the related regulatory mechanisms. A rat model of TLE was established by intraperitoneal injection of lithium chloride-pilocarpine. These model rats were injected intracerebroventricularly with an miRNA-146a inhibitor and Notch-1 siRNA. Then, neuronal damage and cell apoptosis in the cornu ammonis (CA) 1 and 3 regions of the hippocampus were assessed. SOD and MDA levels in the hippocampus were detected by chromatometry, and IL-1β, IL-6, and IL-18 levels were detected by ELISA. Then, we evaluated the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus. The interaction between Notch-1 and miRNA-146a was assessed by a dual luciferase reporter gene assay. A rat model of TLE was successfully established, which exhibited significantly increased miRNA-146a expression in the hippocampus. Silencing of miRNA-146a significantly alleviated the neuronal damage and cell apoptosis in the CA1 and CA3 regions of the hippocampus in TLE rats and decreased MDA, IL-1β, IL-6, and IL-18 levels and increased SOD levels in the hippocampus of TLE rats. In addition, silencing of miRNA-146a significantly decreased the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus of TLE rats. Notch-1 was identified as a target of miRNA-146a and silencing of Notch-1 aggravated the neuronal damage in the CA1 and CA3 regions. Silencing of miRNA-146a alleviated the neuronal damage in the hippocampus of TLE rats by down-regulating Notch-1.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1

et al. 2019

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“…Similarly, zileuton was shown to decrease spike-wave discharges in pilocarpine epileptic rats [168], strongly suggesting that leukotrienes play a role in epilepsy.…”

Section: Cerebral Localization Of Cyslt Receptorsmentioning

confidence: 99%

“…Pharmacological inhibition of LOX using dual inhibitors of LOX/COX pathway phenidone [ 160 , 166 ], which decreased the production of CysLTs, or BW755C [ 167 ] attenuated the seizure activity. Similarly, zileuton was shown to decrease spike-wave discharges in pilocarpine epileptic rats [ 168 ], strongly suggesting that leukotrienes play a role in epilepsy.…”

Section: Cerebral Localization Of Cyslt Receptorsmentioning

confidence: 99%

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

Gelosa

Colazzo

Tremoli

et al. 2017

Mediators of Inflammation

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Cysteinyl leukotrienes (CysLTs) are potent lipid mediators widely known for their actions in asthma and in allergic rhinitis. Accumulating data highlights their involvement in a broader range of inflammation-associated diseases such as cancer, atopic dermatitis, rheumatoid arthritis, and cardiovascular diseases. The reported elevated levels of CysLTs in acute and chronic brain lesions, the association between the genetic polymorphisms in the LTs biosynthesis pathways and the risk of cerebral pathological events, and the evidence from animal models link also CysLTs and brain diseases. This review will give an overview of how far research has gone into the evaluation of the role of CysLTs in the most prevalent neurodegenerative disorders (ischemia, Alzheimer's and Parkinson's diseases, multiple sclerosis/experimental autoimmune encephalomyelitis, and epilepsy) in order to understand the underlying mechanism by which they might be central in the disease progression.

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“…Changes of Notch 1 receptor have been shown in the animal model of temporal lobe epilepsy as well as absence epilepsy in the WAG/Rij rats. (X. Liu, Yang, Yin, & Deng, ; Sha et al, ).…”

Section: Introductionmentioning

confidence: 99%

Discrepancies of Notch 1 receptor during development of chronic seizures

Saffarzadeh

Mousavi

Lotfinia

et al. 2019

Journal Cellular Physiology

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The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer’s disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end‐stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end‐stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures.

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Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

Cited by 16 publications

References 65 publications

Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1

Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

Discrepancies of Notch 1 receptor during development of chronic seizures

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