Effects of target deprivation on the morphology and survival of adult dorsal column nuclei neurons.
During development, interaction with target cells plays a critical role in the regulation of survival of afferent neurons. In an attempt to define the role of target cells in the adult central nervous system, the somatodendritic morphology and survival of adult cuneate neurons deprived of their targets by in situ injection of kainic acid in the rat thalamus were studied. In neuron-specific, enolase-immunostained sections, a 20% decrease in the mean longest diameter of the labeled cells was detected at 4 months postlesion. This somatic atrophy was accompanied by a loss of distal dendritic arborizations as observed after labeling by intracellular diffusion of horseradish peroxidase. Cytochrome oxidase staining did not reveal detectable alterations of the metabolic activity of these neurons, and an ultrastructural study also failed to demonstrate major changes in the neuronal somata. Cell counts indicated a much delayed death of 25% of the neurons at 10 months postlesion, whereas no neuronal death was detected at 7 months. The glial cells appeared unaltered both in number and in immunolabeling when using OX-42 antibodies or antiglial fibrillary acidic protein (anti-GFAP) antibodies. Results obtained in this time-course study indicate that neuronal death and alteration of the somatodendritic morphology are much delayed events after excitotoxic loss of targets. Somatodendritic atrophy occurs several months postlesion, and neuronal death occurs close to 1 year after lesion. These results suggest that the hypothesis of a necessary continuous trophic support by target cells does not hold as firmly for the adult central nervous system as during development.
Marty
S
S
INSERM Unité 421, Faculté de Médecine, Créteil, France.
Peschanski
M
M
D000818:Animals; D001284:Atrophy; D001933:Brain Stem / Q000166:cytology* / Q000648:ultrastructure; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D048429:Cell Size; D003712:Dendrites / Q000502:physiology; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007608:Kainic Acid; D008854:Microscopy, Electron; D009457:Neuroglia / Q000166:cytology; D009475:Neurons, Afferent / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D009562:Nissl Bodies / Q000473:pathology; D015388:Organelles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000166:cytology* / Q000648:ultrastructure; D013997:Time Factors
D003576:Electron Transport Complex IV; D007608:Kainic Acid