Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid

Sloka S. Iyengar, John J. LaFrancois, Daniel Friedman, Liam J. Drew, Christine A. Denny, Nesha S. Burghardt, Melody V. Wu, Jenny Hsieh, René Hen, Helen E. Scharfman

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4. hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21. hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30. min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA.

Original languageEnglish (US)
Pages (from-to)135-149
Number of pages15
JournalExperimental Neurology
Volume264
DOIs
StatePublished - Feb 1 2015

Fingerprint

Kainic Acid
Neurogenesis
Seizures
Dentate Gyrus
Neurons
Ethosuximide
Convulsants
Parahippocampal Gyrus
Olfactory Bulb
Pharmacogenetics
Brain
Prosencephalon
Neuroglia
Anticonvulsants
Brain Stem
Mammals
Injections

Keywords

  • Convulsive seizures
  • Dentate gyrus
  • Electroencephalography (EEG)
  • Epilepsy
  • Hippocampus
  • Inhibition
  • Interictal spikes (IIS)
  • Subgranular zone (SGZ)

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Iyengar, S. S., LaFrancois, J. J., Friedman, D., Drew, L. J., Denny, C. A., Burghardt, N. S., ... Scharfman, H. E. (2015). Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid. Experimental Neurology, 264, 135-149. https://doi.org/10.1016/j.expneurol.2014.11.009

Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid. / Iyengar, Sloka S.; LaFrancois, John J.; Friedman, Daniel; Drew, Liam J.; Denny, Christine A.; Burghardt, Nesha S.; Wu, Melody V.; Hsieh, Jenny; Hen, René; Scharfman, Helen E.

In: Experimental Neurology, Vol. 264, 01.02.2015, p. 135-149.

Research output: Contribution to journalArticle

Iyengar, SS, LaFrancois, JJ, Friedman, D, Drew, LJ, Denny, CA, Burghardt, NS, Wu, MV, Hsieh, J, Hen, R & Scharfman, HE 2015, 'Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid', Experimental Neurology, vol. 264, pp. 135-149. https://doi.org/10.1016/j.expneurol.2014.11.009
Iyengar SS, LaFrancois JJ, Friedman D, Drew LJ, Denny CA, Burghardt NS et al. Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid. Experimental Neurology. 2015 Feb 1;264:135-149. https://doi.org/10.1016/j.expneurol.2014.11.009
Iyengar, Sloka S. ; LaFrancois, John J. ; Friedman, Daniel ; Drew, Liam J. ; Denny, Christine A. ; Burghardt, Nesha S. ; Wu, Melody V. ; Hsieh, Jenny ; Hen, René ; Scharfman, Helen E. / Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid. In: Experimental Neurology. 2015 ; Vol. 264. pp. 135-149.
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