title: Induction of brain-derived neurotrophic factor in plaque-associated glial cells of aged APP23 transgenic mice.
abstract: Brain-derived neurotrophic factor (BDNF) is a versatile neurotrophic factor that has been implicated in cell survival, cell differentiation, axonal growth, and activity-dependent synaptic plasticity. Changes in BDNF expression have also been reported during the course of several neurological disorders, including Alzheimer's disease (AD). The role of BDNF in AD, however, has remained elusive. To learn more about this neurotrophic factor, we investigated BDNF expression in brain of amyloid precursor protein overexpressing mice (APP23 transgenic mice). In situ hybridization revealed BDNF mRNA signals associated with amyloid plaques. Laser microdissection in combination with quantitative RT-PCR demonstrated a sixfold increase of BDNF mRNA in the immediate plaque vicinity, a threefold increase in a tissue ring surrounding the plaque, and control levels in interplaque areas comparable with those measured in age-matched nontransgenic mice. Double immunofluorescence localized BDNF to microglial cells and astrocytes surrounding the plaque. Cortical BDNF protein levels were quantified by ELISA demonstrating a >10-fold increase compared with age-matched controls. This upregulation of BDNF protein significantly correlated with the beta-amyloid load in the transgenic animals. Taken together, our data demonstrate a plaque-associated upregulation of BDNF in APP23 transgenic mice and implicate this neurotrophin in the regulation of inflammatory and axonal growth processes in the plaque vicinity.
authors.affiliation: Institute of Clinical Neuroanatomy, J. W. Goethe University, D-60590 Frankfurt, Germany.
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Burbach
authors.forename: Rainer
authors.initials: R
authors.lastname: Hellweg
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
authors.forename: Domenico
authors.initials: D
authors.lastname: Del Turco
authors.forename: Uwe
authors.initials: U
authors.lastname: Deicke
authors.forename: Dorothee
authors.initials: D
authors.lastname: Abramowski
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)