Thus, in theory, BMP9 by increasing both NGF protein synthesis and, concurrently, upregulating NGF receptor expression in septal neurons, could rescue their cholinergic phenotype upon delayed administration following fimbria-fornix lesions. Although we did not explore this possibility, this could have direct translational implications in the search for treatments of disease states affecting basal forebrain cholinergic neurons with dysfunction of NGF and its receptors, such as Alzheimer��s disease. BMP signaling plays an important role in both neurogenesis and gliogenesis. The interaction between BMP and other growth factors, such as FGF2, is central in the maturation of the nervous NS 11021 system and could also, play a significant role during neuronal cell repair following brain injury. We found that BMP9 significantly reduced FGF2 levels in both lesioned and unlesioned hippocampi, whereas the levels of this growth factor remained unchanged in vehicle treated mice regardless of the lesion. FGF2 promotes the proliferation of progenitor cells, preventing their exit from the cell cycle. BMPs, in contrast, tend to reduce cell proliferation, promoting cell differentiation and cell lineage restriction. During development, these apparently opposing effects may contribute to a specific cell fate. Our data suggest that, following fimbria-fornix transection, BMP9 may indirectly support and maintain the cholinergic phenotype by an alternative mechanism, namely, by reducing FGF levels and maintaining the state of cholinergic differentiation. In spite of an apparently complete, microscopically verified, transection of fimbria fornix, detectable levels of ACh still persisted 6-days post-lesion in the hippocampus, albeit drastically reduced, and treatment with BMP9 partially blocked this loss of hippocampal ACh content. The most likely explanation for this is apparent upregulation of ACh synthesis and/or sprouting of the nerve SDZ 205-557 hydrochloride terminals of the septal cholinergic neurons that project to the hippocampus using the supracallosal pathway and a ventral pathway. In addition, early studies have pointed out the possible presence of intrinsic cholinergic neurons in the hippocampus and we and others have observed CHT-immunoreactive cells in the rat hilus. Note that in the current study we found a significant increase in CHT protein content evoked by BMP9 in the lesioned hippocampus, but not the unlesioned side.