Ultrastructural analysis of the progression of neurodegeneration in the septum following fimbria-fornix transection.
The fimbria-fornix transection paradigm has been used as a model of retrograde neurodegeneration within the medial septal nucleus and anterograde degeneration of axon terminals within the lateral septal nucleus. Because the maintenance and survival of neurons may depend on the integrity of both efferents and afferents, the ultrastructure of neurons in the medial septal nucleus and dorsolateral septal nucleus was analysed at three, seven, 14, 30 days, and six months following unilateral transection of the fimbria-fornix in adult rats. Degeneration of axonal and somatodendritic compartments occurred in both nuclei on the side ipsilateral to fimbria-fornix transection. Degeneration of axons and terminals was present by three days and dissipated thereafter, although degenerating axodendritic and axosomatic terminals were still detected at 14-30 days postlesion. Dendrosomal alterations in both septal nuclei manifested as redistribution of organelles, dispersion and loss of rough endoplasmic reticulum, formation of membrane-bound vacuolar cisternae and membranous inclusions, loss of cytoplasmic matrix, and dispersion of chromatin throughout the nucleoplasmic matrix. These changes occurred in the absence of apparent ultrastructural damage to mitochondria and condensation of the nucleus. Dendritic pathology in both the medial and dorsolateral septal nuclei was most prominent at 14-30 days postlesion, but the neuropil recovered to control appearance by six months postlesion. In contrast, the cytoplasmic rarefaction and vacuolation of neuronal cell bodies were persistent in both the medial septal nucleus and the dorsolateral septal nucleus. We conclude that, following disconnection from the hippocampus, ultrastructural abnormalities occur within neurons in both the medial and lateral septal nuclei. The characteristics and time-course for these changes are similar in both nuclei. The neuropilar degeneration was transient, in contrast to the neuronal cell body injury which was persistent and was morphologically consistent with long-term neuronal atrophy.
Ginsberg
S D
SD
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Martin
L J
LJ
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D019771:Axotomy; D001921:Brain / Q000033:anatomy & histology / Q000648:ultrastructure; D016923:Cell Death / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000473:pathology*; D009457:Neuroglia / Q000502:physiology / Q000648:ultrastructure; D019581:Neuropil / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley