The NMDAR Subunit NR2B Expression is Modified in Hippocampus after Repetitive Seizures

Abstract

NMDA receptor is involved in synaptic plasticity, learning, memory and neurological diseases like epilepsia and it is the major mediator of excitotoxicity. NR2B-containing NMDA receptors may be playing a crucial role in epileptic disorders. In the present study the effect of the convulsant drug 3-mercaptopropionic acid (MP) repetitive administration (4-7 days) on the hippocampal NR2B subunit was studied. A significant decrease in NR2B in the whole hippocampus was observed after MP4 with a tendency to recover to normal values in MP7 by western blot assay. Immunohistochemical studies showed a decrease in several CA1 and CA2/3 strata (21-73%). MP7 showed a reversion of the drop observed at 4 days in stratum oriens, pyramidal cell layer in CA1, CA2/3 and CA1 stratum radiatum. A significant fall in the lacunosum molecular layer of both areas and stratum radiatum of CA2/3 was observed. The immunostaining in MP4 showed a decrease in the granulare layer from dentate gyrus (20%), in hillus (71%) and subicullum (63%) as compared with control and these decreases were similar at MP7 values. Results showed decreases in NR2B subunit expression in different areas following repeated MP-induce seizures, suggesting that NR2B expression is altered depending on the diverse hippocampal input and output signals of each region that could be differently involved in modulating MP-induced hyperactivity.

3-Mercaptopropionic Acid-Induced Seizures Decrease NR2B Expression in Purkinje Cells: Cyclopentyladenosine Effect

“…The decreased NR2B expression in the cerebellum (present finding) and in certain hippocampal areas and strata (Auzmendi et al 2009) may indicate an injury or cognitive inhibition considering that NR2B subunit overexpression in mice have been observed with cognitive enhancement (Cull-Candy et al 2001).…”

Neuroimaging of frontal–limbic dysfunction in schizophrenia and epilepsy-related psychosis: Toward a convergent neurobiology

“…To our knowledge, this explanation for schizophrenia has not yet been applied to epilepsy-related psychosis, despite many relevant parallels, such as the fact that antibodies directed against the NMDA receptor cause a syndrome of epilepsy and psychosis [128]; NMDA-r antagonists not only cause psychosis, they prevent seizures and are antiepileptogenic [129]; and there are significant alterations in NMDA receptors in excised epileptogenic lesions [130]. Based on these findings, we wonder whether SLPE could relate to down-regulation of NMDA receptors [131–133] in response to chronic seizure-induced excess glutamate. Similarly, the controversial entity of forced normalization could be transient NMDA hypofunction during a period of relatively diminished glutamate release.…”

Down-Regulation of Synaptic GluN2B Subunit-Containing N-methyl-d-aspartate Receptors: A Physiological Brake on CA1 Neuron α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Hyperexcitability during Benzodiazepine Withdrawal

“…Ionotropic glutamate receptors have been implicated in neuronal development, synaptic plasticity (Dingledine et al, 1999), excitotoxicity (Auzmendi et al, 2009), and addiction (Lau and Zukin, 2007;Tan et al, 2010). AMPAR and NMDAR, the two major subtypes of ionotropic glutamate receptors in the central nervous system, undergo bidirectional modulation during FZP withdrawal (Van Sickle et al, 2004).…”