The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats

Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad

doi:10.4103/0253-7613.174394

Cited by 32 publications

(5 citation statements)

References 25 publications

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“…In this study, we found that injection of miRNA-146a siRNA significantly reduced MDA levels and increased SOD levels in the hippocampus of TLE rats. Our findings are consistent with a previous study on vitamin E. It has been reported that vitamin E pre-treatment significantly decreased MDA levels and increased SOD levels in the hippocampus of TLE rats, and this reduction in hippocampal oxidative stress decreased the severity and incidence of seizures and improved retrieval and recall in passive avoidance [34]. We suspect that silencing of miRNA-146a may alleviate the neural damage in the hippocampus of TLE rats by promoting ROS scavenging.…”

Section: Discussionsupporting

confidence: 93%

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: 93%

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 finding might be explained by affliction of common neuron groups (possibly located in the hippocampus) involved in both spatial memory and seizure induction. This argument is supported by the observation that intra-hippocampal kainate injection impairs both spatial memory and induces seizures in parallel in an animal model of epilepsy ( 26 ).…”

Section: Discussionmentioning

confidence: 85%

Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis

Pişkin,

Korkmaz,

Ulusoy

et al. 2023

Front. Immunol.

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ObjectiveAutoimmune encephalitis (AE) is a distinct neuro-immunological disorder associated with the production of autoantibodies against neuronal proteins responsible for pharmacoresistant seizures, cognitive decline and behavioral problems. To establish the causal link between leucine-rich glioma inactivated 1 (LGI1) antibody and seizures, we developed an in-vivo antibody-mediated AE rat model in which serum antibodies (IgG) obtained from blood samples of leucine-rich glioma inactivated 1 (LGI1) protein antibody (IgG) positive encephalitis patients were passively transferred into non-epileptic Wistar rats. Serum IgG of N-methyl-d-aspartate receptor (NMDAR) antibody positive patients were used as positive control since the pathogenicity of this antibody has been previously shown in animal models.MethodsTotal IgG obtained from the pooled sera of NMDAR and LGI1-IgG positive patients with epileptic seizures and healthy subjects was applied chronically every other day for 11 days into the cerebral lateral ventricle. Spontaneous seizure development was followed by electroencephalography. Behavioral tests for memory and locomotor activity were applied before and after the antibody infusions. Then, pentylenetetrazol (PTZ) was administered intraperitoneally to evaluate seizure susceptibility. Immunohistochemistry processed for assessment of hippocampal astrocyte proliferation and expression intensity of target NMDAR and LGI1 antigens.ResultsNo spontaneous activity was observed during the antibody infusions. PTZ-induced seizure stage was significantly higher in the NMDAR-IgG and LGI1-IgG groups compared to control. Besides, memory deficits were observed in the NMDAR and LGI1-IgG groups. We observed enhanced astrocyte proliferation in NMDAR- and LGI1-IgG groups and reduced hippocampal NMDAR expression in NMDAR-IgG group.SignificanceThese findings suggest that neuronal surface auto-antibody administration induces seizure susceptibility and disturbed cognitive performance in the passive transfer rat model of LGI1 AE, which could be a potential in-vivo model for understanding immune-mediated mechanisms underlying epileptogenesis and highlight the potential targets for immune-mediated seizures in AE patients.

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“…This vitamin has been shown to exert a neuroprotective action on ferroptosis-dependent pentilenetetrazole-kindled model of epilepsy (Alzoubi et al, 2019;Zhang et al, 2022). Moreover, Vitamin E treatment was reported to attenuate the severity and incidence of seizures and to improve passive avoidance learning and memory in kainateinduced temporal lobe epilepsy in rats (Kiasalari et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The ferroptosis inducer RSL3 triggers interictal epileptiform activity in mice cortical neurons

Giustizieri

Petrillo

D’Amico

et al. 2023

Front. Cell. Neurosci.

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Epilepsy is a neurological disorder characterized by recurrent seizures, which result from excessive, synchronous discharges of neurons in different brain areas. In about 30% of cases, epileptic discharges, which vary in their etiology and symptomatology, are difficult to treat with conventional drugs. Ferroptosis is a newly defined iron-dependent programmed cell death, characterized by excessive accumulation of lipid peroxides and reactive oxygen species. Evidence has been provided that ferroptosis is involved in epilepsy, and in particular in those forms resistant to drugs. Here, whole cell patch clamp recordings, in current and voltage clamp configurations, were performed from layer IV principal neurons in cortical slices obtained from adult mouse brain. Application of the ferroptosis inducer RAS-selective lethal 3 (RSL3) induced interictal epileptiform discharges which started at RSL3 concentrations of 2 μM and reached a plateau at 10 μM. This effect was not due to changes in active or passive membrane properties of the cells, but relied on alterations in synaptic transmission. In particular, interictal discharges were dependent on the excessive excitatory drive to layer IV principal cells, as suggested by the increase in frequency and amplitude of spontaneously occurring excitatory glutamatergic currents, possibly dependent on the reduction of inhibitory GABAergic ones. This led to an excitatory/inhibitory unbalance in cortical circuits. Interictal bursts could be prevented or reduced in frequency by the lipophilic antioxidant Vitamin E (30 μM). This study allows identifying new targets of ferroptosis-mediated epileptic discharges opening new avenues for the treatment of drug-resistant forms of epilepsy.

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The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats

Cited by 32 publications

References 25 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

Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis

The ferroptosis inducer RSL3 triggers interictal epileptiform activity in mice cortical neurons

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