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The ROI were analyzed for cell number in at least three non-consecutive sections per animal. As expected, multiple CHATimmunoreactive cells within the medial septum and the diagonal band were observed. Mice subjected to the fimbria-fornix transection and infused with PBS alone, were characterized by a 50% loss in the number of the CHAT-positive cells in the medial septum ipsilateral to the lesion. Sparing of the cholinergic neurons was evident with increasing doses of BMP9, and there was little or no loss of these neurons in animals receiving 15 and 38 ng/h of BMP9, indicating that BMP9 was highly effective in preventing the loss of CHAT-positive neurons whose axons had been transected. It is well established that basal forebrain cholinergic neurons benefit from hippocampal NGF as a trophic factor for survival and maintenance of their cholinergic phenotype. We have recently shown that BMP9 can induce NGF as an autocrine/ paracrine cholinergic trophic factor in developing basal forebrain neurons. To determine whether BMP9 had an effect on NGF content in the hippocampus of fimbria-fornix lesioned mice and, perhaps, explain some of our data described above, we analyzed the levels of NGF protein in the hippocampus of these mice by ELISA. NGF levels were increased in the hippocampus of BMP9 treated mice by 47% and 61% on the lesioned and unlesioned side, respectively, compared to the corresponding levels in the hippocampus of PBS infused control animals. These data show that BMP9 administered at the time of a septohippocampal transection prevents the loss of septal cholinergic neurons normally observed with this type of injury. They also show that BMP9 partially prevents the loss of ACh and other cholinergic markers in the lesioned hippocampus, and that BMP9 induces hippocampal NGF that could in part be responsible in mediating the above effects. Unilateral fimbria-fornix transection has been one of the most successful models in the study of the effects of growth factors on Carcinine dihydrochloride injured septal cholinergic neurons. Following this procedure, the ipsilateral septal neurons show downregulated expression of CHAT and of another cholinergic marker the vesicular ACh transporter. It is generally thought that following fimbria fornix axotomy the cholinergic septal neurons tend not to degenerate and die, instead, devoid of contact with their targets these neurons lose their cholinergic phenotype without dying. Whether the actions of BMP9 observed here result from a direct effect of BMP9 on the cholinergic neurons subjected to the lesion, or indirectly mediated by other factors, or both, remains uncertain. It has been shown that, following-fimbria fornix transection, NGF can rescue septal neurons from the loss of their cholinergic phenotype when administered at the time of the lesion, as is the case for BMP9 in the present study. Thus, our data from this and previous studies suggest that BMP9 bears similarity to the actions of NGF in a variety of ways including increased ACh production and CHAT expression. As noted above we found that BMP9 can induce the synthesis and release of NGF in septal cultures, and that NGF can partially mediate some of the effects of BMP9. Moreover, like NGF, BMP9 can increase gene expression of NGF receptor NGFR-p75. NGFR-p75 would be expected to potentiate NGF signaling via the NGF signaling receptor, TrkA whose hippocampal expression is also increased in BMP9-infused mice. 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 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 terminals of the septal cholinergic neurons that project to the hippocampus using the supracallosal pathway and a ventral pathway.