Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus

Tang, Feng Ru; Chia, Shwn Chin; Chen, P.M; Gao, Hong; Lee, W.L; Yeo, Tianrong; Burgunder, Jean‐Marc; Probst, A.; Sim, Melvyn; Ling, Eng‐Ang

doi:10.1016/j.eplepsyres.2004.04.002

Cited by 59 publications

(58 citation statements)

References 31 publications

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“…2) including the hilus of the dentate gyrus, hippocampal subfields CA1 and CA3, different layers of the entorhinal cortex, and the amygdale. Extensive gliosis and atrophy were also noticed in the hippocampus as previously reported (Borges et al, 2003;Liu et al, 1994;Tang et al, 2004). In marked contrast with control rats, chronically epileptic rats exhibited a highly significant reduction in the BK channel immunoreactivity intensity in the hilus of dentate gyrus and CA3 stratum lucidum (Fig.…”

Section: Down-regulation Of Bk Channels In Axons and Terminal Fields supporting

confidence: 80%

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Otalora¹,

Hernandez²,

Arshadmansab³

et al. 2008

Brain Research

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In the hippocampus, BK channels are preferentially localized in presynaptic glutamatergic terminals including mossy fibers where they are thought to play an important role regulating excessive glutamate release during hyperactive states. Large conductance calcium-activated potassium channels (BK, MaxiK, Slo) have recently been implicated in the pathogenesis of genetic epilepsy. However, the role of BK channels in acquired mesial temporal lobe epilepsy (MTLE) remains unknown. Here we used immunohistochemistry, laser scanning confocal microscopy (LSCM), western immunoblotting and RT-PCR to investigate the expression pattern of the alpha-pore forming subunit of BK channels in the hippocampus and cortex of chronically epileptic rats obtained by the pilocarpine model of MTLE. All epileptic rats experiencing recurrent spontaneous seizures exhibited a significant down-regulation of BK channel immunostaining in the mossy fibers at the hilus and stratum lucidum of the CA3 area. Quantitative analysis of immunofluorescence signals by LSCM revealed a significant 47% reduction in BK channel in epileptic rats when compared to age-matched non-epileptic control rats. These data correlate with a similar reduction in BK channel protein levels and transcripts in the cortex and hippocampus. Our data indicate a seizure-related down-regulation of BK channels in chronically epileptic rats. Further functional assays are necessary to determine whether altered BK channel expression is an acquired channelopathy or a compensatory mechanism affecting the network excitability in MTLE. Moreover, seizure-mediated BK down-regulation may disturb neuronal excitability and presynaptic control at glutamatergic terminals triggering exaggerated glutamate release and seizures.

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Section: Down-regulation Of Bk Channels In Axons and Terminal Fields supporting

confidence: 80%

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Otalora¹,

Hernandez²,

Arshadmansab³

et al. 2008

Brain Research

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“…It was supported by our study in the rat pilocarpine model showing drastic reduction of mGluR8 in the outer one-third of the molecular layer of the dentate gyrus [68]. This model also showed up regulation of mGluR1 in the stratum oriens [69], mGluR2/3 in the stratum lacunosum molecular [64] and mGluR8 in the entire molecular layer of the dentate gyrus [68] 24 h after pilocarpine induced status epilepticus. However, in the mouse pilocarpine model, Chen et al [21], showed an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR 1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6, but not in the FVB/N strain, suggesting differential expression of group I and III mGluR in different species and strains of animals.…”

Section: Changes Of Mglurs In Animal Model Of Seizures Status Epilepsupporting

confidence: 63%

“…Similar to the kindling model, mGluR5 and mGluR2/3 were also increased in astrocytes in kainate-induced epileptic seizures, [25,75]. However, in the pilocarpine model, no upregulation of mGluR2/3 and mGluR5 in astrocytes was demonstrated [64]. In the hippocampi of epileptic patients, Glazier et al [32] reported decrease in levels of mGluR1 and mGluR2.…”

Section: Changes Of Mglurs In Animal Model Of Seizures Status Epilepmentioning

confidence: 83%

“…Up regulation of mGluR3 and 5 in reactive astrocytes in kindling model suggests that glialneuronal communication may play a role in the course of epileptogenesis [5]. However, in neuronal elements of the basolateral amygdala in kindling model, and in the hippocampus of the rat and mouse pilocarpine models and of patients with mesial temporal lobe epilepsy, group II mGluRs were down regulated [34,64]. Decreased sensitivity to group III mGluR agonists in the lateral perforant path in kindling [24,29,37,40] and pilocarpine [13] models indicates the loss of feedback inhibition mediated by group III mGluRs, particularly that of subtype mGluR8 or mGluR7 respectively.…”

Section: Changes Of Mglurs In Animal Model Of Seizures Status Epilepmentioning

confidence: 90%

“…Parallel in vivo studies showed anticonvulsive effect of agonists and antagonists of mGluRs in different animal models ( Tables 1-4 or group II mGluR agonist 2R, 4R-APDC [64] were administered systemically during pilocarpine induced status epilepticus, no anticonvulsive effect was observed; it suggests that further studies have to be done before the conclusion that agonists and antagonists of mGluRs are antiepileptic is drawn.…”

Section: Anticonvulsive But Not Antiepileptic Effect Of Agonists Andmentioning

confidence: 99%

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Agonists and Antagonists of Metabotropic Glutamate Receptors: Anticonvulsants and Antiepileptogenic Agents?

Tang

2005

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Anticonvulsant and neuroprotective effects of agonist and antagonist of metabotropic glutamate receptors (mGluRs) have been known for more than 10 years from multiple studies. However, it is not certain whether these candidate drugs are also antiepileptic and antiepileptogenic, as few studies included the chronic stages to determine whether spontaneous recurrent seizures could be prevented or stopped. Even in the acute stage, differences in experimental design such as timing and route of administration of candidate drugs, age, species and strain of experimental animal and experimental model make it difficult to determine the anticonvulsant and neuroprotective effects of each candidate drug. This paper, reviews in vivo neuropharmacological studies on agonsists and antagonists of mGluRs in different seizure and epilepsy models in last more than ten years. By combining with our neuropharmacological studies on the effect of mGluR agonists and antagonists in the mouse pilocarpine model of temporal lobe epilepsy, an ideal model for future development of mGluR agonists and antagonists as antiepileptogenic drugs will be proposed.

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Ca_v1.2, Ca_v1.3, and Ca_v2.1 in the mouse hippocampus during and after pilocarpine‐induced status epilepticus

Long

Tang

et al. 2007

Hippocampus

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Calcium binding proteins are well known to be expressed by different groups of hippocampal interneurons; however, whether voltage-dependent calcium channels (Ca(v)) are also localized in these neurons, changed during and after status epilepticus (SE), and involved in epileptic activity have not been reported. In the present study, we showed the colocalization of three subtypes of voltage-gated calcium channels (Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1) with different calcium binding proteins such as calbindin (CB), calretinin (CR), and parvalbumin (PV). At early stages during and after pilocarpine-induced status epilepticus (PISE), significant changes of expression of Ca(v)1.2, Ca(v)1.3 (L-type), and Ca(v)2.1 (P/Q-type) were found in different groups of hippocampal neurons. Induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes was shown at 1 week and 2 months after PISE. At the latter time point, higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunoposivie neurons were observed in gliotic CA1 area. We therefore conclude that voltage-gated calcium channels are expressed by different groups of hippocampal interneurons in the mouse. At acute stages during and after PISE, up- or down-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in functionally different groups of interneurons in CA1 area may be related to the changes of their plasticity. Up-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in granule cells may be directly related to the occurrence of SE. The induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes at 1 week and 2 months after PISE suggests that Ca(v)1.3 or Ca(v)2.1-related calcium signaling in reactive astrocytes may be involved in initiation, maintenance or spread of seizure activity. In gliotic CA1 area at chronic stage (i.e., 2 months after PISE), the occurrence of higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunopositive neurons may suggest that such colocalizations may be linked to the survival or loss of particular group of hippocampal neurons.

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Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus

Cited by 59 publications

References 31 publications

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Agonists and Antagonists of Metabotropic Glutamate Receptors: Anticonvulsants and Antiepileptogenic Agents?

Ca_v1.2, Ca_v1.3, and Ca_v2.1 in the mouse hippocampus during and after pilocarpine‐induced status epilepticus

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Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus

Cited by 59 publications

References 31 publications

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Agonists and Antagonists of Metabotropic Glutamate Receptors: Anticonvulsants and Antiepileptogenic Agents?

Cav1.2, Cav1.3, and Cav2.1 in the mouse hippocampus during and after pilocarpine‐induced status epilepticus

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Ca_v1.2, Ca_v1.3, and Ca_v2.1 in the mouse hippocampus during and after pilocarpine‐induced status epilepticus