Skip to Main content Skip to Navigation
Journal articles

Increased cyclin D1 in vulnerable neurons in the hippocampus after ischaemia and epilepsy: a modulator of in vivo programmed cell death?

Abstract : Several observations suggest that delayed neuronal death in ischaemia, epilepsy and other brain disorders includes an apoptotic component, involving programmed cell death (PCD). PCD is hypothesized to result, in part, from aberrant control of the cell cycle. Because they are instrumental in mitosis, cyclins D are key markers to evaluate whether neurons indeed progress into the cell cycle in situations of pathology. Therefore, we investigated in rat brains, the expression of cyclins D in the delayed neuronal death that occurs following transient global ischaemia and kainate-induced seizures. Following a four-vessel occlusion insult, quantitative in situ hybridization revealed a highly significant and persistent 100% increase of cyclin D1 mRNA in the vulnerable pyramidal neurons of the CA1 hippocampal region. Ischaemia also induced a smaller and transient cyclin D1 mRNA increase in the resistant CA3 area and dentate gyrus. In contrast, the cyclin D2 and D3 mRNAs, expressed constitutively in the adult rat hippocampus, were not upregulated. Following kainate-induced seizures, cyclin D1 mRNA was induced in the vulnerable CA3 region, and to a lesser extent, in non-vulnerable regions. Cyclin D1 immunohistochemistry revealed increased protein levels in the cytoplasm and nucleus of neurons commited to die after ischaemia. Double labelling experiments indicate that cyclin D1 is also expressed in reactive astrocytes but not in microglial cells. Finally, we report that in neurons, cyclin D1 expression peaks before nuclear condensation and the appearance of DNA fragmentation. We propose that cyclin D1, when expressed at high levels in lesioned neurons, may act as a modulator of apoptosis.
Document type :
Journal articles
Complete list of metadatas

Cited literature [67 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00486281
Contributor : Roman Tyzio <>
Submitted on : Tuesday, May 25, 2010 - 2:46:01 PM
Last modification on : Friday, March 27, 2020 - 2:20:29 AM
Long-term archiving on: : Wednesday, November 30, 2016 - 10:12:05 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

  • HAL Id : inserm-00486281, version 1
  • PUBMED : 9987030

Collections

Citation

Serge Timsit, Santiago Rivera, Philippe Ouaghi, Frédérique Guischard, Evelyne Tremblay, et al.. Increased cyclin D1 in vulnerable neurons in the hippocampus after ischaemia and epilepsy: a modulator of in vivo programmed cell death?. European Journal of Neuroscience, Wiley, 1999, 11 (1), pp.263-78. ⟨inserm-00486281⟩

Share

Metrics

Record views

268