Irradiation exacerbates cortical cytopathology in the Eker rat model of tuberous sclerosis complex, but does not induce hyperexcitability

Naranzogt Tschuluun, H. Jürgen Wenzel, Philip A Schwartzkroin

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multi-organ pathologies. Most TSC patients exhibit seizures, usually starting in early childhood. The neuropathological hallmarks of the disease - cortical tubers, containing cytopathological neuronal and glial cell types - appear to be the source of seizure initiation. However, the contribution of these aberrant cell populations to TSC-associated epilepsies is not fully understood. To gain further insight, investigators have attempted to generate animal models with TSC-like brain abnormalities. In the current study, we focused on the Eker rat, in which there is a spontaneous mutation of the TSC2 gene (TSC2+/-). We attempted to exacerbate TSC-like brain pathologies with a "second-hit" strategy-exposing young pups to ionizing irradiation of different intensities, and at different developmental timepoints (between E18 and P6). We found that the frequency of occurrence of dysmorphic neurons and giant astrocytes was strongly dependent on irradiation dose, and weakly dependent on timing of irradiation in Eker rats, but not in irradiated normal controls. The frequency of TSC-like pathology was progressive; there were many more abnormal cells at 3 months compared to 1 month post-irradiation. Measures of seizure propensity (flurothyl seizure latency) and brain excitability (paired-pulse and post-tetanic stimulation studies in vitro), however, showed no functional changes associated with the appearance of TSC-like cellular abnormalities in irradiated Eker rats.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalEpilepsy Research
Volume73
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Tuberous Sclerosis
Seizures
Pathology
Brain
Flurothyl
Neuroglia
Astrocytes
Epilepsy
Animal Models
Research Personnel
Neurons
Mutation
Population
Genes

Keywords

  • Brain pathology
  • Dysmorphic neurons
  • Eker rat
  • Hyperexcitability
  • Seizures
  • Tuberous sclerosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Neurology

Cite this

Irradiation exacerbates cortical cytopathology in the Eker rat model of tuberous sclerosis complex, but does not induce hyperexcitability. / Tschuluun, Naranzogt; Wenzel, H. Jürgen; Schwartzkroin, Philip A.

In: Epilepsy Research, Vol. 73, No. 1, 01.2007, p. 53-64.

Research output: Contribution to journalArticle

@article{8090fdff018e433fb8d8d68cf5b36398,
title = "Irradiation exacerbates cortical cytopathology in the Eker rat model of tuberous sclerosis complex, but does not induce hyperexcitability",
abstract = "Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multi-organ pathologies. Most TSC patients exhibit seizures, usually starting in early childhood. The neuropathological hallmarks of the disease - cortical tubers, containing cytopathological neuronal and glial cell types - appear to be the source of seizure initiation. However, the contribution of these aberrant cell populations to TSC-associated epilepsies is not fully understood. To gain further insight, investigators have attempted to generate animal models with TSC-like brain abnormalities. In the current study, we focused on the Eker rat, in which there is a spontaneous mutation of the TSC2 gene (TSC2+/-). We attempted to exacerbate TSC-like brain pathologies with a {"}second-hit{"} strategy-exposing young pups to ionizing irradiation of different intensities, and at different developmental timepoints (between E18 and P6). We found that the frequency of occurrence of dysmorphic neurons and giant astrocytes was strongly dependent on irradiation dose, and weakly dependent on timing of irradiation in Eker rats, but not in irradiated normal controls. The frequency of TSC-like pathology was progressive; there were many more abnormal cells at 3 months compared to 1 month post-irradiation. Measures of seizure propensity (flurothyl seizure latency) and brain excitability (paired-pulse and post-tetanic stimulation studies in vitro), however, showed no functional changes associated with the appearance of TSC-like cellular abnormalities in irradiated Eker rats.",
keywords = "Brain pathology, Dysmorphic neurons, Eker rat, Hyperexcitability, Seizures, Tuberous sclerosis",
author = "Naranzogt Tschuluun and Wenzel, {H. J{\"u}rgen} and Schwartzkroin, {Philip A}",
year = "2007",
month = "1",
doi = "10.1016/j.eplepsyres.2006.08.003",
language = "English (US)",
volume = "73",
pages = "53--64",
journal = "Epilepsy Research",
issn = "0920-1211",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Irradiation exacerbates cortical cytopathology in the Eker rat model of tuberous sclerosis complex, but does not induce hyperexcitability

AU - Tschuluun, Naranzogt

AU - Wenzel, H. Jürgen

AU - Schwartzkroin, Philip A

PY - 2007/1

Y1 - 2007/1

N2 - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multi-organ pathologies. Most TSC patients exhibit seizures, usually starting in early childhood. The neuropathological hallmarks of the disease - cortical tubers, containing cytopathological neuronal and glial cell types - appear to be the source of seizure initiation. However, the contribution of these aberrant cell populations to TSC-associated epilepsies is not fully understood. To gain further insight, investigators have attempted to generate animal models with TSC-like brain abnormalities. In the current study, we focused on the Eker rat, in which there is a spontaneous mutation of the TSC2 gene (TSC2+/-). We attempted to exacerbate TSC-like brain pathologies with a "second-hit" strategy-exposing young pups to ionizing irradiation of different intensities, and at different developmental timepoints (between E18 and P6). We found that the frequency of occurrence of dysmorphic neurons and giant astrocytes was strongly dependent on irradiation dose, and weakly dependent on timing of irradiation in Eker rats, but not in irradiated normal controls. The frequency of TSC-like pathology was progressive; there were many more abnormal cells at 3 months compared to 1 month post-irradiation. Measures of seizure propensity (flurothyl seizure latency) and brain excitability (paired-pulse and post-tetanic stimulation studies in vitro), however, showed no functional changes associated with the appearance of TSC-like cellular abnormalities in irradiated Eker rats.

AB - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multi-organ pathologies. Most TSC patients exhibit seizures, usually starting in early childhood. The neuropathological hallmarks of the disease - cortical tubers, containing cytopathological neuronal and glial cell types - appear to be the source of seizure initiation. However, the contribution of these aberrant cell populations to TSC-associated epilepsies is not fully understood. To gain further insight, investigators have attempted to generate animal models with TSC-like brain abnormalities. In the current study, we focused on the Eker rat, in which there is a spontaneous mutation of the TSC2 gene (TSC2+/-). We attempted to exacerbate TSC-like brain pathologies with a "second-hit" strategy-exposing young pups to ionizing irradiation of different intensities, and at different developmental timepoints (between E18 and P6). We found that the frequency of occurrence of dysmorphic neurons and giant astrocytes was strongly dependent on irradiation dose, and weakly dependent on timing of irradiation in Eker rats, but not in irradiated normal controls. The frequency of TSC-like pathology was progressive; there were many more abnormal cells at 3 months compared to 1 month post-irradiation. Measures of seizure propensity (flurothyl seizure latency) and brain excitability (paired-pulse and post-tetanic stimulation studies in vitro), however, showed no functional changes associated with the appearance of TSC-like cellular abnormalities in irradiated Eker rats.

KW - Brain pathology

KW - Dysmorphic neurons

KW - Eker rat

KW - Hyperexcitability

KW - Seizures

KW - Tuberous sclerosis

UR - http://www.scopus.com/inward/record.url?scp=33846109991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846109991&partnerID=8YFLogxK

U2 - 10.1016/j.eplepsyres.2006.08.003

DO - 10.1016/j.eplepsyres.2006.08.003

M3 - Article

C2 - 17011168

AN - SCOPUS:33846109991

VL - 73

SP - 53

EP - 64

JO - Epilepsy Research

JF - Epilepsy Research

SN - 0920-1211

IS - 1

ER -