Targeting NMDA Receptors in Epilepsy

Ghasemi, Mehdi; Dehpour, Ahmad Reza

doi:10.1007/978-3-642-40282-1_32

Cited by 2 publications

(2 citation statements)

References 187 publications

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“…38,39 So far, massive efforts in basic and clinical research of NMDARs have been made during the past three decades, and they are emerging as promising new targets for epilepsy therapy. [40][41][42] Therefore, STK24 overexpression may promote excitatory synaptic transmission in epileptic neurons through a certain interaction with the NMDAR complex.…”

Section: Discussionmentioning

confidence: 99%

STK24 modulates excitatory synaptic transmission in epileptic hippocampal neurons

Yang

Jiang

et al. 2020

CNS Neurosci Ther

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Introduction A large amount of literature has indicated that excitatory synaptic transmission plays a crucial role in epilepsy, but the detailed pathogenesis still needs to be clarified. Methods In the present study, we used samples from patients with temporal lobe epilepsy, pentylenetetrazole‐kindled mice, and Mg 2+ ‐free‐induced epileptic cultured hippocampal neurons to detect the expression pattern of STK24. Then, the whole‐cell recording was carried out after STK24 overexpression in the Mg 2+ ‐free‐induced epileptic cultured hippocampal neurons. In addition, coimmunoprecipitation was performed to detect the association between endogenous STK24 and main subunits of NMDARs and AMPARs in the hippocampus of PTZ‐kindled mice. Results Here, we reported that STK24 was specifically located in epileptic neurons of human and pentylenetetrazole‐kindled mice. Meanwhile, the expression of STK24 was significantly down‐regulated in these samples which are mentioned above. Besides, we found that the amplitude of miniature excitatory postsynaptic currents was increased in STK24 overexpressed epileptic hippocampal cultured neurons, which means the excitatory synaptic transmission was changed. Moreover, the coimmunoprecipitation, which further supported the previous experiment, indicated an association between STK24 and the subunits of the NMDA receptor. Conclusion These findings expand our understanding of how STK24 involved in the excitatory synaptic transmission in epilepsy and lay a foundation for exploring the possibility of STK24 as a drug target.

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Section: Discussionmentioning

confidence: 99%

STK24 modulates excitatory synaptic transmission in epileptic hippocampal neurons

Yang

Jiang

et al. 2020

CNS Neurosci Ther

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“…On the other hand, it is well known that the overactivation of the glutamatergic system plays a fundamental role in epilepsy (Urbań ska et al 1992). The NMDA receptor activity contributes to neuronal excitation and is linked to the pathophysiology of epilepsy (Ghasemi and Dehpour 2014). It is well determined that NMDA receptor blockers possess antiepileptic activity (Sato et al 1988;Cotton et al 1993;Freitas et al 2006;Vataev et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide andN-methyl-d-aspartate receptor

Amini-Khoei

Kordjazy

Haj-Mirzaian

et al. 2018

Can. J. Physiol. Pharmacol.

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Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-d-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor N-l-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, l-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDA receptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

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Targeting NMDA Receptors in Epilepsy

Cited by 2 publications

References 187 publications

STK24 modulates excitatory synaptic transmission in epileptic hippocampal neurons

STK24 modulates excitatory synaptic transmission in epileptic hippocampal neurons

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide andN-methyl-d-aspartate receptor

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