title: NGF rescues hippocampal cholinergic neuronal markers, restores neurogenesis, and improves the spatial working memory in a mouse model of Huntington's Disease.
abstract: BACKGROUND
  Recent studies in Huntington's disease (HD) mouse models and patients suggest that hippocampal neurons and their cholinergic afferents are involved in the cognitive deficits seen in the disease. Nerve growth factor (NGF) is an essential regulator of cholinergic neuronal survival and neurotransmission.
  
  
  OBJECTIVE
  We asked whether NGF might be involved in HD and if intra-cerebroventricular infusion of NGF can rescue hippocampal cholinergic neuronal markers, restore neurogenesis, and improve the spatial working memory in R6/1 mouse model of HD.
  
  
  METHODS
  We quantified NGF protein level by enzyme-linked immunosorbent assay (ELISA), intracerebroventricularly infused NGF, assessed cholinergic neuronal markers by Western blotting and quantitative RT-PCR, evaluated neurogenesis by immunohistochemistry, and studied spatial working memory using radial maze.
  
  
  RESULTS
  By quantifying NGF protein in the hippocampus of the R6/1 mice at different ages, we found progressive decreases in NGF protein levels. We then increased NGF levels in the R6/1 mice through intra-cerebroventricular infusion. We observed elevations of the cholinergic neurochemical markers vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) in the hippocampus and in the septal region, which contain the cell bodies of basal forebrain cholinergic neurons (BFCNs), but not in the striatum that harbors cholinergic interneurons. Finally, we found that NGF infusion also restored hippocampal neurogenesis and improved spatial working memory.
  
  
  CONCLUSIONS
  Our results suggest that intracerebral injections of NGF might be a valuable therapy against cognitive symptoms in HD and should be further studied in HD animal models and patients.
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Hongyu
authors: H
authors: Zhang
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Géraldine H
authors: GH
authors: Petit
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Philip M
authors: PM
authors: Gaughwin
authors: Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Christian
authors: C
authors: Hansen
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Srikanth
authors: S
authors: Ranganathan
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Xiaoyi
authors: X
authors: Zuo
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Ruben
authors: R
authors: Smith
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Laurent
authors: L
authors: Roybon
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Patrik
authors: P
authors: Brundin
authors: Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors: William C
authors: WC
authors: Mobley
authors: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Jia-Yi
authors: JY
authors: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006816:Huntington Disease / Q000378:metabolism; D007150:Immunohistochemistry; D057967:Infusions, Intraventricular; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D055495:Neurogenesis / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020932:Nerve Growth Factor
keywords: Nerve growth factor; R6/1 mice; cholinergic function; huntington's disease; neurogenesis