The anticonvulsant activity and cerebral protection of chronic lithium chloride via NMDA receptor/nitric oxide and phospho-ERK

Jafari, Razieh Mohammad; Ghahremani, Mohammad Hossein; Rahimi, Nastaran; Shadboorestan, Amir; Rashidian, Amir; Esmaeili, Jamileh; Mehr, Shahram Ejtemaei; Dehpour, Ahmad Reza

doi:10.1016/j.brainresbull.2017.10.015

Cited by 21 publications

(10 citation statements)

References 47 publications

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“…Similar to what is reported for PILO, the autophagy inducer lithium produces anticonvulsive and neuroprotective effects in murine models of PTZ-induced seizures [135]. While acute lithium administration (30 mg/kg) enhances the proconvulsive properties of PTZ, chronic pretreatment with lithium (7 days, 10 mg/kg) significantly increases the seizure threshold.…”

Section: Pentylenetetrazole (Ptz)-induced Seizuressupporting

confidence: 75%

“…At the same time, lithium confers neuroprotection in primary cerebellar cultured neurons by counteracting glutamate-induced excitotoxicity. In fact, both anti-epileptogenic and neuroprotective effects of lithium are reversed by the coadministration of an NMDA receptor antagonist [135]. It is remarkable that similar to the protective effects of mTOR inhibitors against the neurotoxic convulsant quinolinic acid [58], lithium protects against glutamate-induced neurotoxicity, and such an effect is associated with autophagy activation, mostly related to GSK3β inhibition [119][120][121][122][123].…”

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 99%

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mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

Limanaqi

Biagioni

Busceti

et al. 2020

IJMS

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Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure-induced neuronal damage. The implication of autophagy in epileptogenesis and maturation phenomena related to seizure activity is supported by evidence indicating that autophagy is involved in the molecular mechanisms which are implicated in epilepsy. In general, mTOR-dependent autophagy regulates the proliferation and migration of inter-/neuronal cortical progenitors, synapse development, vesicular release, synaptic plasticity, and importantly, synaptic clustering of GABAA receptors and subsequent excitatory/inhibitory balance in the brain. Similar to autophagy, the ubiquitin–proteasome system is regulated downstream of mTOR, and it is implicated in epileptogenesis. Thus, mTOR-dependent cell-clearing systems are now taking center stage in the field of epilepsy. In the present review, we discuss such evidence in a variety of seizure-related disorders and models. This is expected to provide a deeper insight into the molecular mechanisms underlying seizure activity.

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Section: Pentylenetetrazole (Ptz)-induced Seizuressupporting

confidence: 75%

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 99%

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

Limanaqi

Biagioni

Busceti

et al. 2020

IJMS

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“…NO enhances the expression of cAMP response element binding protein (CREB) to mediate the response to BDNF (Riccio et al, 2006). NO also mediates glutamate-NMDA receptor (NMDAr) signaling in neurons (Jafari et al, 2018;Wu and Tymianski, 2018).…”

Section: Phosphatase Activitymentioning

confidence: 99%

Soluble Epoxide Hydrolase and Brain Cholesterol Metabolism

Domingues

Callai-Silva

Piovesan

et al. 2020

Front. Mol. Neurosci.

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“…It has been reported that the activity of ERK is related to seizure development (Curia et al, 2013; Mohammad Jafari et al, 2018). Because the phosphorylation of ERK is closely related to the expression of SR in the hippocampus, we next tested whether ERK activity was required for the effects of SR manipulation on seizure development.…”

Section: Resultsmentioning

confidence: 99%

D-Serine Contributes to Seizure Development via ERK Signaling

Chen

et al. 2019

Front. Neurosci.

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A seizure is one of the leading neurological disorders. NMDA receptor-mediated neuronal excitation has been thought to be essential for epileptogenesis. As an endogenous co-agonist of the NMDA receptor, D-serine has been suggested to play a role in epileptogenesis. However, the underlying mechanisms remain unclear. In the current study, we investigated the effects of antagonizing two key enzymes in D-serine metabolism on the development of seizures and the downstream signaling. Our results showed that serine racemase (SR), a key enzyme in regulating the L-to-D-serine conversion, was significantly up-regulated in hippocampal astrocytes in rats and patients who experienced seizure, in comparison with control rats and patients. L-aspartic acid β-hydroxamate (LaaβH), an inhibitor of SR, significantly prolonged the latencies of seizures, shortened the durations of seizures, and decreased the total EEG power in rats. In contrast, D-amino acid oxidase inhibitor 5-chlorobenzo[d]isoxazol-3-ol (CBIO), which can increase D-serine levels, showed the opposite effects. Furthermore, our data showed that LaaβH and CBIO significantly affected the phosphorylation of Extracellular Signal-regulated Kinase (ERK). Antagonizing or activating ERK could significantly block the effects of LaaβH/CBIO on the occurrence of seizures. In summary, our study revealed that D-serine is involved in the development of epileptic seizures, partially through ERK signaling, indicating that the metabolism of D-serine may be targeted for the treatment of epilepsy.

show abstract

The anticonvulsant activity and cerebral protection of chronic lithium chloride via NMDA receptor/nitric oxide and phospho-ERK

Cited by 21 publications

References 47 publications

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

Soluble Epoxide Hydrolase and Brain Cholesterol Metabolism

D-Serine Contributes to Seizure Development via ERK Signaling

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