Calbindin-D28K is increased in the ventral horn of spinal cord by neuroprotective factors for motor neurons.

Abstract

Slow glutamate-mediated neuronal degeneration is implicated in the pathophysiology of motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The calcium-binding proteins calbindin-D28K and parvalbumin have been reported to protect neurons against excitotoxic insults. Expression of calbindin-D28K is low in adult human motor neurons, and vulnerable motor neurons additionally may lack parvalbumin. Thus, it has been speculated that the lack of calcium-binding proteins may, in part, be responsible for early degeneration of the population of motor neurons most vulnerable in ALS. Using a rat organotypic spinal cord slice system, we examined whether the most potent neuroprotective factors for motor neurons can increase the expression of calbindin-D28K or parvalbumin proteins in the postnatal spinal cord. After 4 weeks of incubation of spinal cord slices with 1) glial cell line-derived neurotrophic factor (GDNF), 2) neurturin, 3) insulin-like growth factor I (IGF-I), or 4) pigment epithelium-derived factor (PEDF), the number of calbindin-D28K -immunopositive large neurons (>20 μm) in the ventral horn was higher under the first three conditions, but not after PEDF, compared with untreated controls. Under the same conditions, parvalbumin was not upregulated by any neuroprotective factor. The same calbindin increase was true of IGF-I and GDNF in a parallel glutamate toxicity model of motor neuron degeneration. Taken together with our previous reports from the same model, which showed that all these neurotrophic factors can potently protect motor neurons from slow glutamate injury, the data here suggest that upregulation of calbindin-D28K by some of these factors may be one mechanism by which motor neurons can be protected from glutamate-induced, calcium-mediated excitotoxicity.