Expression of bone morphogenetic proteins in the brain during normal aging and in 6-hydroxydopamine-lesioned animals.

Bone morphogenetic proteins (BMPs), BMP receptors (BMPRs), and endogenous BMP antagonists have been found to be critically important for the development of the central nervous system (CNS) and peripheral organs in mammals. There is also increasing evidence that this system has significant activity in the adult CNS. Accordingly, we studied the regional distribution of endogenous BMP ligand proteins, receptors, and antagonists during aging and after lesion of the midbrain dopamine pathways produced by 6-hydroxydopamine (6-OHDA). We found that there were only small changes in the levels of these molecules as a function of age. Interestingly, levels of BMP 7 and noggin, a BMP antagonist, were uniquely elevated in substantia nigra. Moreover, after lesions of the midbrain dopamine system by 6-hydroxydopamine, there was a marked reduction in levels of all BMP ligands, receptors and antagonists bilaterally in both substantia nigra and hippocampus. There were also differential changes in BMP ligands, receptors, and antagonists in the cortex and striatum after such lesions. Taken together, our results indicate significant expression of BMP-related molecules in the adult and aging brain, and suggest a dynamic and differential regulation of these molecules after perturbations.