NERVE GROWTH-FACTOR INCREASES CALCIUM-BINDING PROTEIN (CALBINDIN-D28K) IN RAT OLFACTORY-BULB

Calbindin-D28K (CaBP28K) is a soluble intracellular protein capable of sequestering micromolar concentrations of calcium. The in vivo regulation of CaBP28K by recombinant human nerve growth factor (rhNGF) was studied in adult, male rats. Via Alzet 2002 pumps, each rat received, for 14 days, a lateral ventricle infusion (i.c.v.; n = 5-6/group) of 12-mu-l PBS/day containing 1.0-mu-g cytochrome C (control) or an equal amount of rhNGF. Six other animals received a vehicle or rhNGF infusion into the central neostriatum. CaBP28K was elevated by 75% (P < 0.01) in the olfactory bulb following i.c.v. rhNGF in each of two experiments and was not altered in the temporal cortex, hippocampus, olfactory tubercle, cerebellum, or neostriatum. Direct striatal injections of rhNGF did not alter CaBP28K in the neostriatum or other regions (including the olfactory bulb). The increases in olfactory bulb CaBP28K Protein levels were verified via Western blot analysis. CaBP28K immunocytochemistry revealed that 33% of olfactory bulb neurons are immunoreactive for CaBP28K and that the number or proportion of immunoreactive neurons did not change with i.c.v. infusions of rhNGF, suggesting that exogenously delivered rhNGF augments the content of CaBP28K in olfactory bulb neurons that normally express the protein. Endogenous NGF may function as a neuroprotective factor by enhancing the ability of these cells to sequester cytoplasmic calcium and retard calcium-mediated neurodegeneration.