CHT is responsible for the high affinity transport of choline into synaptic nerve terminals and can be the rate limiting step in ACh synthesis. Previous mouse model studies have shown that upregulation of CHT expression can provide functional compensation in states of cholinergic dysfunction. In our lesion experiments, the loss of septohippocampal input to the lesioned hippocampus could render intrahippocampal cholinergic neurons more susceptible to BMP9, and upregulate CHT protein content to compensate for the loss of extrinsic cholinergic innervation. In addition, our results show that BMP9 significantly increased CHAT protein content in the unlesioned hippocampi indicating that it increases CHAT expression in adult basal forebrain cholinergic neurons as it does during development. In the lesioned hippocampi treated with BMP9 CHAT protein levels were not statistically different than those in PBS-treated intact and lesioned controls, suggesting that BMP9 treatment tended to reduce the lesion-evoked loss of the hippocampal CHAT. In conclusion our data show that intracerebral administration of BMP9 protects the axotomized septal cholinergic neurons from the loss of their neurotransmitter phenotype and increases hippocampal expression of NGF, a critical growth factor for these neurons. Together the results indicate that BMP9 may be further explored as a therapeutic factor for these neurons in conditions characterized by their malfunction. CD-1 male mice were used between 40 and 60 days of age. Mice were deeply anesthetized with a mixture of ketamine and xylazine and administered a single injection of prophylactic antibiotic therapy. Their heads were shaved, and the mice were placed in a stereotaxic apparatus. All interventions were performed aseptically on a sterile field. A midsagittal incision was performed on the scalp, and a subcutaneous tunnel was JW 642 opened between the shoulder blades, where the pumps were implanted. The periosteum on the surface of the skull was removed by gently rubbing with a sterile Q-tip. Once the bregma had been identified, the tip of the ICV cannula device held in the stereotaxic apparatus was positioned at coordinates bregma 20.5 mm, right-lateral 1 mm. A hole was then opened in the skull and the cannula device was lowered and fixed in place with Loctite-454 adhesive. The tip of the cannula was located in the right lateral SB 205384 ventricle at a depth of 2 mm from the surface of the skull.