title: Transduced PTD-BDNF fusion protein protects against beta amyloid peptide-induced learning and memory deficits in mice.
abstract: Brain-derived neurotrophic factor (BDNF) promotes the survival and differentiation of hippocampal, cortical, and basal forebrain cholinergic neurons. However, the efficacy of BDNF via peripheral (i.v.) administration is limited by the lack of transport of the neurotrophin through the blood-brain barrier (BBB) in vivo. The present study describes that the i.v. administered recombinant human BDNF (rhBDNF) conjugated with a protein transduction domain (PTD ) is able to survive and promote the growth of hippocampal neurons impaired by Abeta25-35 (10 microM) in vitro and transport through the BBB in vivo. The Morris water maze test indicated that the i.v. PTD-rhBDNF improved the spatial learning and memory of mice impaired by the aggregated Abeta25-35. The peripherally administered PTD-rhBDNF exhibited neuroprotective effects in brain and raise the possibility of delivery of the exogenous rhBDNF in treatment of the brain diseases.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Zhou
authors.forename: Ze Guo
authors.initials: ZG
authors.lastname: Feng
authors.forename: Ben Li
authors.initials: BL
authors.lastname: Yuan
authors.forename: Shou Zhong
authors.initials: SZ
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Hen Yan
authors.initials: HY
authors.lastname: Qu
authors.forename: Man Ji
authors.initials: MJ
authors.lastname: Sun
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D010446:Peptide Fragments; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C074636:amyloid beta-protein (25-35)