Thalamic neuron apoptosis emerges rapidly after cortical damage in immature mice

JoAnne E Natale, Y. Cheng, L. J. Martin

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

In adults and children, head trauma can have long-term neuropathological and functional consequences. The thalamus is a major site of remote neurodegeneration after cortical damage in adult humans and experimental animals, but less is known about thalamic responses to cortical injury in the immature brain. This study introduces an in vivo model of axotomy/target deprivation-induced neuronal apoptosis in the dorsal lateral geniculate nucleus of the thalamus produced by unilateral ablation of the occipital cortex in the immature mouse. We specifically examined whether occipital cortex ablation in the immature brain causes apoptotic death of projection neurons in the dorsal lateral geniculate nucleus. After unilateral occipital cortex aspiration, 10-day-old C57BL/6 mice were recovered for up to 28 days. Fluorogold-prelabeled thalamocortical projection neurons were apoptotic at 36-48 h after ablation. The structural progression of apoptosis in the immature lateral geniculate nucleus reveals typical chromatolytic morphology by 18-24 h, followed by cytoplasmic shrinkage and chromatin condensation characteristic of end-stage apoptosis after 36-48 h. Electron microscopy confirmed the presence of apoptosis. This study shows internucleosomal DNA fragmentation and expression of cleaved caspase-3 occurs rapidly, being noted first at 18 h, well before the peak of apoptotic cell death occurring at 36 h after cortical damage in the immature brain. From these data we suggest that axotomy/target deprivation-induced cell death in the immature brain may: (1) differ from that previously reported in adult mice with respect to the time required for progression to cell death; (2) be mediated by caspase-3 activation.

Original languageEnglish (US)
Pages (from-to)665-676
Number of pages12
JournalNeuroscience
Volume112
Issue number3
DOIs
StatePublished - Jul 5 2002
Externally publishedYes

Keywords

  • Axotomy
  • Brain injury
  • Caspase-3
  • DNA damage
  • Neuronal cell death
  • Retrograde neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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