Non-competitive antagonists of NMDA and AMPA receptors decrease seizure-induced c-fos protein expression in the cerebellum and protect against seizure symptoms in adult rats

Tóth, Zoltán; Mihály, András; Mátyás, Adrienne; Krisztin-Péva, Beáta

doi:10.1016/j.acthis.2018.02.004

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…Brain microdialysis detected a significant increase of tissue glutamate during 4-aminopyridine (4-AP)-induced seizures [41]. The non-competitive antagonist of the AMPA receptor, GYKI 52466, reduced the seizure symptoms and increased the seizure latency [42,43], but it did not prevent the swelling of the hippocampal astrocytes in 4-AP seizures [42]. The pharmacological antagonists of KARs prevented the acute pilocarpine seizure [44].…”

Section: Functional Alterations Expression and Distribution Of Imentioning

confidence: 99%

“…The combination of NBQX (an AMPAR antagonist) and ifenprodil (an NMDAR antagonist) exerted promising antiepileptic actions in kainate-induced murine epilepsy [45]. Antagonists of NMDAR inhibited the Glu release [46] and seizure symptoms [43,46], as well as prevented the post-ictal neuronal damage [47] and the long-term reactive plasticity of the dentate granule cells [45].…”

Section: Functional Alterations Expression and Distribution Of Imentioning

confidence: 99%

“…The endogenous downregulation of the iGluRs may protect the neurons and the synapses against the toxic effects of Glu [48]. Neuroprotection in acute epileptic fits against the neurotoxicity of Glu can be achieved by blocking the iGluRs with pharmacological antagonists [42,43,44,45,46,47,48,49]. However, the neuronal damage and degeneration, which develop in the chronic seizure, rearrange the wiring of the brain [45,50].…”

Section: Functional Alterations Expression and Distribution Of Imentioning

confidence: 99%

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The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

Mihály

2019

IJMS

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Ionotropic glutamate receptors (iGluRs) mediate the synaptic and metabolic actions of glutamate. These iGluRs are classified within the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type, kainate-type, and N-methyl-d-aspartate (NMDA)-type functional receptor families. The iGluR assemblies are regulated by transcription, alternative splicing, and cytoplasmic post-translational modifications. The iGluR subunit proteins are transported from the endoplasmic reticulum, inserted into the synaptic membranes, and anchored at their action site by different scaffolding and interacting proteins. The functional properties of iGluRs depend on their subunit composition, the amino acid sequence of the protein domains, and the scaffolding proteins in the synaptic membranes. The iGluRs are removed from the membranes by enzymatic action and endocytosis. Hippocampal iGluRs are rearranged through the upregulation and downregulation of the subunits following deafferentation and epileptic seizures. The rearrangement of iGluRs and the alteration of their subunit composition transform neurons into “pathological” cells, determining the further plasticity or pathology of the hippocampal formation. In the present review, we summarize the expression of AMPA, kainate, and NMDA receptor subunits following deafferentation, repeated mild seizures, and status epilepticus. We compare our results to literature descriptions, and draw conclusions as to the reactive plasticity of iGluRs in the hippocampus.

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Section: Functional Alterations Expression and Distribution Of Imentioning

confidence: 99%

Section: Functional Alterations Expression and Distribution Of Imentioning

confidence: 99%

Section: Functional Alterations Expression and Distribution Of Imentioning

confidence: 99%

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The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

Mihály

2019

IJMS

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“…Following post-fixation, the brains were cryoprotected overnight in 30% sucrose in PBS, pH 7.4, and 24 μm thick sagittal plane sections were cut from the vermis using a freezing microtome (Reichert-Jung Cryocut 1800). Sagittal plane sections of the vermis were used to investigate seizure-induced activation of the vermal cerebellar lobules (Tóth et al, 2015;2018). Free-floating tissue sections were processed for c-fos immunohistochemistry.…”

Section: Animals and Treatmentmentioning

confidence: 99%

“…4-AP works by blocking K + channels in different neuronal populations, thereby increasing transmitter release and inducing epileptic neuronal activity (Thesleff 1980;Kovács et al, 2003). Given that the major cerebellar afferents operate with glutamic acid transmitters, the postsynaptic effects of 4-AP elicited convulsions can be long-lasting and can be detected with immunohistochemistry (Tóth et al, 2015;2018). C-fos protein immunohistochemistry can be used as marker of neuronal activity, and for semiquantitative mapping of activated neurons (Willoughby et al, 1995;Mihály et al, 1997;Herdegen and Leah, 1998;Tóth et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of the c-fos protein and synaptophysin in zebrin II positive and zebrin II negative cerebellar cortical areas in 4-aminopyridine seizures

Krisztin-Péva¹,

Mihály²,

Tóth³

2019

Acta Neurobiologiae Experimentalis

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The present study examined temporal activation patterns of rat cerebellar cortical neurons in 4-aminopyridine induced seizures, using c-fos protein as a marker of neuronal activity. C-fos-containing cells were counted in each cerebellar cortical layer, and cell count was compared between zebrin II positive and zebrin II negative bands of the lobules of the vermis and cerebellar hemispheres. We found significant activation of granule cells and interneurons of the molecular layer in zebrin II positive bands. The Purkinje cells, in contrast, exhibited non-significant, scattered c-fos immunoreactivity across all bands.Fluctuation of synaptophysin expression in the mossy fibre rosettes of the granular layer was determined via light microscopic immunohistochemistry. We detected a transient, significant decrease in synaptophysin staining density following 4-aminopyridine seizures, which may indicate short-term synaptic depression. We also identified different timing of increased c-fos expression in the neurons of the cerebellar cortex in different cortical zones. In particular, the activation pattern of the interneurons of the molecular layer reflected the climbing fibre distribution, reflecting the zonal olivo-cortico-nuclear organization. Seizure-induced activation of the granule cells corresponded with the zebrin II positive zones. This observation raises the possibility that zebrin II positive compartments may be more susceptible to cerebellar convulsions.

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Comparative Assessment of the Effectiveness of Noncompetitive NMDA Receptor Antagonists Amantadine and Hemantane in Morphine Withdrawal Syndrome Model

Колик

Konstantinopolsky

2019

Bull Exp Biol Med

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Non-competitive antagonists of NMDA and AMPA receptors decrease seizure-induced c-fos protein expression in the cerebellum and protect against seizure symptoms in adult rats

Cited by 12 publications

References 43 publications

The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

Differential expression of the c-fos protein and synaptophysin in zebrin II positive and zebrin II negative cerebellar cortical areas in 4-aminopyridine seizures

Comparative Assessment of the Effectiveness of Noncompetitive NMDA Receptor Antagonists Amantadine and Hemantane in Morphine Withdrawal Syndrome Model

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