Regional expression of Fos-like immunoreactivity following seizures in Noda epileptic rat (NER)

Ohno, Yukihiro; Shimizu, Saki; Harada, Yuya; Morishita, Maho; Ishihara, Shizuka; Kumafuji, Kenta; Sasa, Masashi; Serikawa, Tadao

doi:10.1016/j.eplepsyres.2009.07.012

Cited by 20 publications

(10 citation statements)

References 26 publications

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“…Although the cause of the seizures in NER is not clear, tonic-clonic seizures are primarily evoked by activation of forebrain cortico-limbic circuits. No information is available thus far on the role of the hippocampal GABA circuit in NER, whereas the hippocampus has been suggested to play a role in epileptogenesis (Hanaya et al 2002;Ohno et al 2009).…”

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confidence: 99%

Dual mechanisms diminishing tonic GABA_A inhibition of dentate gyrus granule cells in Noda epileptic rats

Pandit

Jeong

et al. 2013

Journal of Neurophysiology

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The Noda epileptic rat (NER), a Wistar colony mutant, spontaneously has tonic-clonic convulsions with paroxysmal discharges. In the present study, we measured phasic and tonic γ-aminobutyric acid A (GABAA) current (I tonic) in NER hippocampal dentate gyrus granule cells and compared the results with those of normal parent strain Wistar rats (WIS). I tonic, revealed by a bicuculline-induced outward shift in holding current, was significantly smaller in NER than in WIS (P < 0.01). The frequency of inhibitory postsynaptic currents (IPSCs) was also significantly lower in NER than in WIS (P < 0.05), without significant differences in the IPSC amplitude or decay time between WIS and NER. I tonic attenuation in NER was further confirmed in the presence of GABA transporter blockers, NO-711 and nipecotic acid, with no difference in neuronal GABA transporter expression between WIS and NER. I tonic responses to extrasynaptic GABAA receptor agonists (THIP and DS-2) were significantly reduced in NER compared with WIS (P < 0.05). Allopregnanolone caused less I tonic increase in NER than in WIS, while it prolonged the IPSC decay time to a similar rate in the two groups. Expression of the GABAA receptor δ-subunit was decreased in the dentate gyrus of NER relative to that of WIS. Taken together, our results showed that a combination of attenuated presynaptic GABA release and extrasynaptic GABAA receptor expression reduced I tonic amplitude and its sensitivity to neurosteroids, which likely diminishes the gating function of dentate gyrus granule cells and renders NER more susceptible to seizure propagation.

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confidence: 99%

Dual mechanisms diminishing tonic GABA_A inhibition of dentate gyrus granule cells in Noda epileptic rats

Pandit

Jeong

et al. 2013

Journal of Neurophysiology

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“…As previously reported (Eells et al ., 2004; Bastlund et al ., 2005), PTZ‐induced GTC seizures enhanced Fos expression in many cerebral regions including the cerebral cortex, amygdala and hippocampus, and the highest Fos expression was observed in the hippocampal DG. Magnolol specifically inhibited Fos expression in certain cortico‐limbic areas, such as the hippocampus and piriform cortical areas, all of which have been implicated in the generation of convulsive seizures and/or epileptogenesis (Ohno et al ., 2009). The hippocampus and piriform cortex are often considered to play major roles in the pathophysiology of temporal lobe seizures (de Guzman et al ., 2004; Gavrilovici et al ., 2006), and the hallmarks of temporal lobe seizures are hippocampal sclerosis and synaptic reorganization in the DG (Magloczky et al ., 2000).…”

Section: Discussionmentioning

confidence: 99%

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice

Chen¹,

Tan

et al. 2011

British Journal of Pharmacology

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BACKGROUND AND PURPOSEThe aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6′, 7, 12-tetramethoxy-2, 2′-dimethyl-1-b-berbaman, C18H18O2) and the mechanisms involved. EXPERIMENTAL APPROACHMice were treated with magnolol (20, 40 and 80 mg·kg -1 ) 30 min before injection with pentylenetetrazol (PTZ, 60 mg·kg -1 , i.p.). The anti-seizure effects of magnolol were analysed using seizure models of behaviour, EEG and in vitro electrophysiology and c-Fos expression in the hippocampus and cortex. KEY RESULTS Magnolol at doses of 40 and 80 mg·kg-1 significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with those of the vehicle-treated animals. EEG recordings showed that magnolol (40 and 80 mg·kg -free model of epileptiform activity, using multi-electrode array recordings in mouse hippocampal slices, magnolol decreased spontaneous epileptiform discharges. Magnolol also significantly decreased seizure-induced Fos immunoreactivity in the piriform cortex, dentate gyrus and hippocampal area CA1. These effects were attenuated by pretreatment with flumazenil. CONCLUSIONS AND IMPLICATIONSThese findings indicate that the inhibitory effects of magnolol on epileptiform activity were mediated by the GABAA/benzodiazepine receptor complex.

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“…The brain was removed from the skull and placed in 4% paraformaldehyde solution for 24 h. After postfixation, the brain was dehydrated and embedded in paraffin. Formalin-fixed and paraffin-embedded hippocampal tissues were cut into 4 μm thick sections and immunohistochemically stained with a goat anti-rat SV2A (dilution 1:100, Santa Cruz Biotechnology) using the ABC method reported previously 14 25 26 27 . SV2A-immunoreactivity was visualized by the diaminobenzidine (DAB)-nickel staining.…”

Section: Methodsmentioning

confidence: 99%

Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission

Tokudome

Okumura

Shimizu

et al. 2016

Sci Rep

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Synaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2aL174Q rat) carrying a Sv2a-targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2aL174Q mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures. In addition, development of kindling associated with repeated PTZ treatments or focal stimulation of the amygdala was markedly facilitated by the Sv2aL174Q mutation. Neurochemical studies revealed that the Sv2aL174Q mutation specifically reduced depolarization-induced GABA, but not glutamate, release in the hippocampus without affecting basal release or the SV2A expression level in GABAergic neurons. In addition, the Sv2aL174Q mutation selectively reduced the synaptotagmin1 (Syt1) level among the exocytosis-related proteins examined. The present results demonstrate that dysfunction of SV2A due to the Sv2aL174Q mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development, illustrating the crucial role of SV2A-GABA system in modulating kindling epileptogenesis.

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Regional expression of Fos-like immunoreactivity following seizures in Noda epileptic rat (NER)

Cited by 20 publications

References 26 publications

Dual mechanisms diminishing tonic GABA_A inhibition of dentate gyrus granule cells in Noda epileptic rats

Dual mechanisms diminishing tonic GABA_A inhibition of dentate gyrus granule cells in Noda epileptic rats

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice

Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission

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Regional expression of Fos-like immunoreactivity following seizures in Noda epileptic rat (NER)

Cited by 20 publications

References 26 publications

Dual mechanisms diminishing tonic GABAA inhibition of dentate gyrus granule cells in Noda epileptic rats

Dual mechanisms diminishing tonic GABAA inhibition of dentate gyrus granule cells in Noda epileptic rats

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice

Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission

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Dual mechanisms diminishing tonic GABA_A inhibition of dentate gyrus granule cells in Noda epileptic rats

Dual mechanisms diminishing tonic GABA_A inhibition of dentate gyrus granule cells in Noda epileptic rats