Interneuronal survival and calbindin-D28k expression following motoneuron degeneration.
Degeneration of both motoneurons and interneurons has been previously observed in amyotrophic lateral sclerosis. It is unclear whether interneuronal loss is due to an intrinsic neuronal defect or if it occurs secondary to loss of their target motoneurons. We have examined the target dependence of interneurons, their survival and alterations in the expression of the calcium binding protein, calbindin-D28k (CB), in the ventral horn of the rat lumbar cord after extensive motoneuron degeneration was induced by unilateral rhizotomy of spinal nerves L2-L6 at postnatal day 3 (P3). Counts of Nissl-stained cells at P21 revealed no significant interneuronal death despite loss of 80% of their target motoneurons. At P6, some motoneurons transiently expressed CB on the operated side compared to the control side. Since most of these cells are destined to die, this transiently increased CB expression may represent an abortive attempt by the axotomised motoneurons to buffer the neurotoxic consequences of high intracellular calcium. In contrast, there was a time-dependent decrease in CB expression in ventral horn interneurons, with only 35% of putative Renshaw cells expressing CB by P21. These results indicate that neonatal interneurons are capable of surviving the loss of their motoneuron targets, but alter their phenotype as indicated by functional alterations in calcium-binding proteins.
Lim
S M
SM
Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Fulham Palace Road, London W6 8RF, UK.
Guiloff
R J
RJ
Navarrete
R
R
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D064092:Calbindin 1; D064026:Calbindins; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D012183:Retrograde Degeneration / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G