Fimbria-fornix transection and excitotoxicity produce similar neurodegeneration in the septum

S. D. Ginsberg, C. Portera-Cailliau, Lee J Martin

Research output: Contribution to journalArticle

Abstract

Fimbria-fornix transection produces neuronal injury in the septum. This cellular pathology is characterized by somatodendritic vacuolar abnormalities in neurons. Because these cellular changes are reminiscent of some of the morphological abnormalities seen with glutamate receptor-mediated excitoxicity, we tested whether excitotoxic injury to the septal complex of adult rats mimics the degeneration observed within the dorsolateral septal nucleus and medial septal nucleus following fimbria-fornix transection. The septal complex was evaluated at various time-points (6 h to 14 days) by light and electron microscopy following unilateral injection of the N-methyl-D- aspartate receptor agonist quinolinate or the non-N-methyl-D-aspartate receptor agonist kainate, and the morphological changes observed were compared to those abnormalities in the medial septal nucleus and dorsolateral septal nucleus at three to 14 days after fimbria-fornix transection. The patterns of cytoplasmic abnormalities and vacuolar injury were morphologically similar in the somatodendritic compartment of neurons following excitotoxicity and axotomy paradigms. These similarities were most evident when comparing the persistently injured neurons in the penumbral regions of the excitotoxic lesions at one to 14 days recovery to neurons in the medial septal nucleus and dorsolateral septal nucleus at seven and 14 days after fimbria-fornix transection. Pretreatment with the N-methyl-D- aspartate receptor antagonist dizocilpine maleate prior to unilateral fimbria-fornix transection attenuated the somatodentritic vacuolar damage found within the ipsilateral dorsolateral and medial septal nuclei at 14 days recovery. Because glutamate is the principal transmitter of hippocampal efferents within the fimbria-fornix, we conclude that postsynaptic glutamate receptor activation participates in the evolution of septal neuron injury following fimbria-fornix transection. Thus, excitotoxicity is a possible mechanism for transneuronal degeneration following central nervous system axotomy.

Original languageEnglish (US)
Pages (from-to)1059-1071
Number of pages13
JournalNeuroscience
Volume88
Issue number4
DOIs
StatePublished - Feb 1999

Fingerprint

Brain Fornix
Septal Nuclei
Neurons
Axotomy
Wounds and Injuries
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Quinolinic Acid
D-Aspartic Acid
Dizocilpine Maleate
Kainic Acid
Glutamic Acid
Electron Microscopy
Central Nervous System
Pathology
Light
Injections

Keywords

  • Axotomy
  • Cell death
  • Glutamate receptors
  • Hippocamposeptal pathway
  • NMDA receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fimbria-fornix transection and excitotoxicity produce similar neurodegeneration in the septum. / Ginsberg, S. D.; Portera-Cailliau, C.; Martin, Lee J.

In: Neuroscience, Vol. 88, No. 4, 02.1999, p. 1059-1071.

Research output: Contribution to journalArticle

Ginsberg, S. D. ; Portera-Cailliau, C. ; Martin, Lee J. / Fimbria-fornix transection and excitotoxicity produce similar neurodegeneration in the septum. In: Neuroscience. 1999 ; Vol. 88, No. 4. pp. 1059-1071.
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