Fimbria-fornix transection and excitotoxicity produce similar neurodegeneration in the septum.
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.
Ginsberg
S D
SD
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Portera-Cailliau
C
C
Martin
L J
LJ
D000818:Animals; D003714:Denervation; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012688:Septum Pellucidum / Q000187:drug effects* / Q000473:pathology*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D017378:Quinolinic Acid; D007608:Kainic Acid