The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy

Ozlem Akman, Medine I. Gulcebi, Nihan Carcak, Sema Ketenci Ozatman, Tugba Eryigit, Solomon L. Moshe, Aristea S. Galanopoulou, Filiz Yilmaz Onat

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of γ-aminobutyric acid γ-aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. Methods Adult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). Results Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. Significance The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.

Original languageEnglish (US)
Pages (from-to)1793-1802
Number of pages10
JournalEpilepsia
Volume56
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Absence Epilepsy
Lidocaine
Seizures
Aminobutyrates
GABAergic Neurons
Pars Reticulata
Parvalbumins
Injections
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Amygdala
gamma-Aminobutyric Acid
Wistar Rats

Keywords

  • GAERS
  • Kindling resistance
  • Parvalbumin
  • Substantia nigra pars reticulata
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Akman, O., Gulcebi, M. I., Carcak, N., Ketenci Ozatman, S., Eryigit, T., Moshe, S. L., ... Yilmaz Onat, F. (2015). The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy. Epilepsia, 56(11), 1793-1802. https://doi.org/10.1111/epi.13204

The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy. / Akman, Ozlem; Gulcebi, Medine I.; Carcak, Nihan; Ketenci Ozatman, Sema; Eryigit, Tugba; Moshe, Solomon L.; Galanopoulou, Aristea S.; Yilmaz Onat, Filiz.

In: Epilepsia, Vol. 56, No. 11, 01.11.2015, p. 1793-1802.

Research output: Contribution to journalArticle

Akman, O, Gulcebi, MI, Carcak, N, Ketenci Ozatman, S, Eryigit, T, Moshe, SL, Galanopoulou, AS & Yilmaz Onat, F 2015, 'The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy', Epilepsia, vol. 56, no. 11, pp. 1793-1802. https://doi.org/10.1111/epi.13204
Akman, Ozlem ; Gulcebi, Medine I. ; Carcak, Nihan ; Ketenci Ozatman, Sema ; Eryigit, Tugba ; Moshe, Solomon L. ; Galanopoulou, Aristea S. ; Yilmaz Onat, Filiz. / The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy. In: Epilepsia. 2015 ; Vol. 56, No. 11. pp. 1793-1802.
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abstract = "Objective Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of γ-aminobutyric acid γ-aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. Methods Adult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). Results Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. Significance The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.",
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AU - Ketenci Ozatman, Sema

AU - Eryigit, Tugba

AU - Moshe, Solomon L.

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AU - Yilmaz Onat, Filiz

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N2 - Objective Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of γ-aminobutyric acid γ-aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. Methods Adult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). Results Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. Significance The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.

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KW - GAERS

KW - Kindling resistance

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