Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy

Jack M. Parent, Robert C. Elliott, Samuel J. Pleasure, Nicholas Barbaro, Daniel H. Lowenstein

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalAnnals of Neurology
Volume59
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

Temporal Lobe Epilepsy
Neurogenesis
Seizures
Dentate Gyrus
Bromodeoxyuridine
Immunohistochemistry
Parahippocampal Gyrus
Naproxen
Pilocarpine
In Situ Hybridization
Hippocampus
Stem Cells
Neurons
Wounds and Injuries

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Parent, J. M., Elliott, R. C., Pleasure, S. J., Barbaro, N., & Lowenstein, D. H. (2006). Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Annals of Neurology, 59(1), 81-91. https://doi.org/10.1002/ana.20699

Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. / Parent, Jack M.; Elliott, Robert C.; Pleasure, Samuel J.; Barbaro, Nicholas; Lowenstein, Daniel H.

In: Annals of Neurology, Vol. 59, No. 1, 01.2006, p. 81-91.

Research output: Contribution to journalArticle

Parent, JM, Elliott, RC, Pleasure, SJ, Barbaro, N & Lowenstein, DH 2006, 'Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy', Annals of Neurology, vol. 59, no. 1, pp. 81-91. https://doi.org/10.1002/ana.20699
Parent JM, Elliott RC, Pleasure SJ, Barbaro N, Lowenstein DH. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Annals of Neurology. 2006 Jan;59(1):81-91. https://doi.org/10.1002/ana.20699
Parent, Jack M. ; Elliott, Robert C. ; Pleasure, Samuel J. ; Barbaro, Nicholas ; Lowenstein, Daniel H. / Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. In: Annals of Neurology. 2006 ; Vol. 59, No. 1. pp. 81-91.
@article{f351fb8184204992b60d37a7886bf587,
title = "Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy",
abstract = "Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures.",
author = "Parent, {Jack M.} and Elliott, {Robert C.} and Pleasure, {Samuel J.} and Nicholas Barbaro and Lowenstein, {Daniel H.}",
year = "2006",
month = "1",
doi = "10.1002/ana.20699",
language = "English (US)",
volume = "59",
pages = "81--91",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy

AU - Parent, Jack M.

AU - Elliott, Robert C.

AU - Pleasure, Samuel J.

AU - Barbaro, Nicholas

AU - Lowenstein, Daniel H.

PY - 2006/1

Y1 - 2006/1

N2 - Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures.

AB - Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures.

UR - http://www.scopus.com/inward/record.url?scp=29944442275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29944442275&partnerID=8YFLogxK

U2 - 10.1002/ana.20699

DO - 10.1002/ana.20699

M3 - Article

VL - 59

SP - 81

EP - 91

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 1

ER -