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Dentate gyrus progenitor cell proliferation after the onset of spontaneous seizures in the tetanus toxin model of temporal lobe epilepsy

Dentate gyrus progenitor cell proliferation after the onset of spontaneous seizures in the tetanus toxin model of temporal lobe epilepsy
Dentate gyrus progenitor cell proliferation after the onset of spontaneous seizures in the tetanus toxin model of temporal lobe epilepsy
Temporal lobe epilepsy alters adult neurogenesis. Existing experimental evidence is mainly from chronic models induced by an initial prolonged status epilepticus associated with substantial cell death. In these models, neurogenesis increases after status epilepticus. To test whether status epilepticus is necessary for this increase, we examined precursor cell proliferation and neurogenesis after the onset of spontaneous seizures in a model of temporal lobe epilepsy induced by unilateral intrahippocampal injection of tetanus toxin, which does not cause status or, in most cases, detectable neuronal loss. We found a 4.5 times increase in BrdU labeling (estimating precursor cells proliferating during the 2nd week after injection of toxin and surviving at least up to 7 days) in dentate gyri of both injected and contralateral hippocampi of epileptic rats. Radiotelemetry revealed that the rats experienced 112 ± 24 seizures, lasting 88 ± 11 s each, over a period of 8.6 ± 1.3 days from the first electrographic seizure. On the first day of seizures, their duration was a median of 103 s, and the median interictal period was 23 min, confirming the absence of experimentally defined status epilepticus. The total increase in cell proliferation/survival was due to significant population expansions of: radial glial-like precursor cells (type I; 7.2 ×), non-radial type II/III neural precursors in the dentate gyrus stem cell niche (5.6 ×), and doublecortin-expressing neuroblasts (5.1 ×). We conclude that repeated spontaneous brief temporal lobe seizures are sufficient to promote increased hippocampal neurogenesis in the absence of status epilepticus.
spontaneous seizures, temporal lobe epilepsy, neurogenesis, Tetanus toxin, apoptosis
0969-9961
492-498
Jiruska, Premysl
8f2d7496-eecd-46f2-b15b-e554e91b7186
Shtaya, Anan B.Y.
5ac06a0f-408d-4b16-b2f2-713e219a5a5e
Bodansky, David M.S.
1368e40d-5b75-4532-84f7-133872c47c0d
Chang, Wei-Chih
e3a54343-dbdb-4f98-a37a-7e5ff760e35e
Gray, William P.
f34a0e23-3cba-4b0a-8676-a1b2c3e4c095
Jefferys, John G.R.
b6d41497-9b42-4e50-92c4-ecf8aef6c997
Jiruska, Premysl
8f2d7496-eecd-46f2-b15b-e554e91b7186
Shtaya, Anan B.Y.
5ac06a0f-408d-4b16-b2f2-713e219a5a5e
Bodansky, David M.S.
1368e40d-5b75-4532-84f7-133872c47c0d
Chang, Wei-Chih
e3a54343-dbdb-4f98-a37a-7e5ff760e35e
Gray, William P.
f34a0e23-3cba-4b0a-8676-a1b2c3e4c095
Jefferys, John G.R.
b6d41497-9b42-4e50-92c4-ecf8aef6c997

Jiruska, Premysl, Shtaya, Anan B.Y., Bodansky, David M.S., Chang, Wei-Chih, Gray, William P. and Jefferys, John G.R. (2013) Dentate gyrus progenitor cell proliferation after the onset of spontaneous seizures in the tetanus toxin model of temporal lobe epilepsy. Neurobiology of Disease, 54, 492-498. (doi:10.1016/j.nbd.2013.02.001).

Record type: Article

Abstract

Temporal lobe epilepsy alters adult neurogenesis. Existing experimental evidence is mainly from chronic models induced by an initial prolonged status epilepticus associated with substantial cell death. In these models, neurogenesis increases after status epilepticus. To test whether status epilepticus is necessary for this increase, we examined precursor cell proliferation and neurogenesis after the onset of spontaneous seizures in a model of temporal lobe epilepsy induced by unilateral intrahippocampal injection of tetanus toxin, which does not cause status or, in most cases, detectable neuronal loss. We found a 4.5 times increase in BrdU labeling (estimating precursor cells proliferating during the 2nd week after injection of toxin and surviving at least up to 7 days) in dentate gyri of both injected and contralateral hippocampi of epileptic rats. Radiotelemetry revealed that the rats experienced 112 ± 24 seizures, lasting 88 ± 11 s each, over a period of 8.6 ± 1.3 days from the first electrographic seizure. On the first day of seizures, their duration was a median of 103 s, and the median interictal period was 23 min, confirming the absence of experimentally defined status epilepticus. The total increase in cell proliferation/survival was due to significant population expansions of: radial glial-like precursor cells (type I; 7.2 ×), non-radial type II/III neural precursors in the dentate gyrus stem cell niche (5.6 ×), and doublecortin-expressing neuroblasts (5.1 ×). We conclude that repeated spontaneous brief temporal lobe seizures are sufficient to promote increased hippocampal neurogenesis in the absence of status epilepticus.

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Published date: June 2013
Keywords: spontaneous seizures, temporal lobe epilepsy, neurogenesis, Tetanus toxin, apoptosis
Organisations: Faculty of Medicine

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Local EPrints ID: 369404
URI: http://eprints.soton.ac.uk/id/eprint/369404
ISSN: 0969-9961
PURE UUID: aad44587-7960-44ca-9e3d-2b9420e22d00

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Date deposited: 25 Sep 2014 12:13
Last modified: 25 Nov 2019 20:39

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Contributors

Author: Premysl Jiruska
Author: Anan B.Y. Shtaya
Author: David M.S. Bodansky
Author: Wei-Chih Chang
Author: William P. Gray
Author: John G.R. Jefferys

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