Effect of lamotrigine on epilepsy‐induced cognitive impairment and hippocampal neuronal apoptosis in pentylenetetrazole‐kindled animal model

Zhang, Bing; Zhang, Jiawei; Wang, Weiping; Dong, Rui‐Fang; Shuang, Tian; Zhang, Chao

doi:10.1002/syn.21945

Cited by 21 publications

(11 citation statements)

References 24 publications

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“…Neural cell death after epilepsy includes necrosis and apoptosis [18]. A previous study shows that number of apoptotic cells has increased at 1 day after seizure and is significantly larger than that in the control group until the seventh week, suggesting that apoptosis runs through the course of epilepsy in rats [19]. Another study shows that neuronal apoptosis partially participates in the formation of hippocampal sclerosis in epileptic patients [19].…”

Section: Discussionmentioning

confidence: 99%

Fyn gene silencing reduces oligodendrocytes apoptosis through inhibiting ERK1/2 phosphorylation in epilepsy

Luo

Zhao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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This study aimed to investigate the effect of Fyn gene silencing on the apoptosis of oligodendrocytes (OLs) in epileptic model in vitro and the involved mechanism. Primary oligodendrocyte pro-genitor cells (OPCs) were separated from rats and differentiated to OLs. Immunofluorescent labeling showed positive expression of A2B5 in OPCs and Olig2 in OLs, suggesting the successful separation of OPCs and OLs. Three Fyn siRNAs (si-Fyn) and Fyn siRNA negative control (NC) were transfected into OLs. Western blot showed that among three si-Fyn groups, si-Fyn3 caused the lowest Fyn expression, so si-Fyn3 was chosen for following experiment. Cells were divided into four groups: Control, Model, NC and si-Fyn. In the Model group, cells were cultured in Mg-free extracellular fluid for 3 h. The morphology of control cells was normal. However, the migration of neurons, the aggregation of cell bodies and the "grid-like" changes of neural networks were observed in the model cells. OLs apoptosis in various groups was assessed by flow cytometry. Expression of Fyn, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in OLs of various groups was evaluated by western blot. Compared with the Control group, the apoptotic rates, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the Model and NC groups increased significantly (p < .05). However, the apoptotic rate, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the si-Fyn group were remarkably smaller than those in the Model group (p < .05). In conclusion, Fyn gene silencing reduced the apoptosis of OLs through inhibiting the phosphorylation of ERK1/2 in epileptic model.

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Section: Discussionmentioning

confidence: 99%

Fyn gene silencing reduces oligodendrocytes apoptosis through inhibiting ERK1/2 phosphorylation in epilepsy

Luo

Zhao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Epilepsy is mainly characterized by the occurrence of spontaneous recurrent seizures (SRS) and high prevalence of comorbidities, such as cognitive impairments, depression, and anxiety, affecting the lives of individuals (Keezer et al., 2016). Chronic epilepsy is characterized by repeated unpredictable seizures, impairing memory in 30–40% of patients under long-term anti-epileptic drugs (AEDs) treatment, so epilepsy and AEDs both are responsible for memory problems (Helmstaedter, 2002; Canevini et al., 2010; Zhang et al., 2017). Despite there being more than 20 mainstream AEDs, they only provide symptomatic treatment rather than interfering with the disease’s mechanism, and 30% of patients do not respond to current AEDs (Remy and Beck, 2005; Chen et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

et al. 2019

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Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.

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“…Pentetrazol, as a central stimulant, can cause neuronal apoptosis in the central nervous system (CNS), especially in the hippocampus area. 5,6 Aer intraperitoneal injection of pentetrazol, rats show a series of behavioral abnormalities and neurological decits. Researches have shown that the concentrations of hydrogen peroxide and nitric oxide are increased while the activities of antioxidant enzymes are decreased following pentetrazol administration in the cultured neurocytes and in a pentetrazol-exposed rat model.…”

Section: Introductionmentioning

confidence: 99%

α-Lipoic acid alleviates pentetrazol-induced neurological deficits and behavioral dysfunction in rats with seizures via an Nrf2 pathway

et al. 2018

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Effect of lamotrigine on epilepsy‐induced cognitive impairment and hippocampal neuronal apoptosis in pentylenetetrazole‐kindled animal model

Cited by 21 publications

References 24 publications

Fyn gene silencing reduces oligodendrocytes apoptosis through inhibiting ERK1/2 phosphorylation in epilepsy

Fyn gene silencing reduces oligodendrocytes apoptosis through inhibiting ERK1/2 phosphorylation in epilepsy

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

α-Lipoic acid alleviates pentetrazol-induced neurological deficits and behavioral dysfunction in rats with seizures via an Nrf2 pathway

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