Interneuronal survival and calbindin-D28K expression following motoneuron degeneration

Degeneration of both motoneurons and interneurons has been previously obser ved in amyotrophic lateral sclerosis, It is unclear whether interneuronal l oss is due to an intrinsic neuronal defect or if it occurs secondary to los s of their target motoneurons. We have examined the target dependence of in terneurons, their survival and alterations in the expression of the calcium binding protein, calbindin-D28k (CB), in the ventral horn of the rat lumba r cord after extensive motoneuron degeneration was induced by unilateral rh izotomy of spinal nerves L2-L6 at postnatal day 3 (P3). Counts of Nissl-sta ined cells at pll revealed no significant interneuronal death despite loss of 80% of their target motoneurons. At P6, some motoneurons transiently exp ressed CB on the operated side compared to the control side. Since most of these cells an destined to die, this transiently increased CB expression ma y 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 resul ts indicate that neonatal interneurons are capable of surviving the loss of their motoneuron targets, but alter their phenotype as indicated by functi onal alterations in calcium-binding proteins. (C) 2000 Elsevier Science B.V . All rights reserved.