title: BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype.
abstract: BACKGROUND
  Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP) 9 is a cholinergic differentiating factor during development both in vivo and in vitro.
  
  
  RESULTS
  To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT)-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75) and TrkA (NTRK1), and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2) protein.
  
  
  CONCLUSIONS
  These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells.
authors.affiliation: Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lopez-Coviella
authors.forename: Tiffany J
authors.initials: TJ
authors.lastname: Mellott
authors.forename: Aletta C
authors.initials: AC
authors.lastname: Schnitzler
authors.forename: Jan K
authors.initials: JK
authors.lastname: Blusztajn
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D019771:Axotomy; D015415:Biomarkers / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D020712:Fornix, Brain / Q000601:surgery; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020665:Septum of Brain / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA; D000109:Acetylcholine