title: Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis.
abstract: Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus. When tested in the Water Maze task, lesioned animals exhibited no reference memory deficit, whereas working memory abilities were seen significantly impaired, as compared with intact or sham-lesioned controls. Stereological analyses confirmed a dramatic noradrenergic neuron loss associated to reduced proliferation, but not survival or differentiation, of 5-bromo-2'deoxyuridine-positive progenitors in the dentate gyrus. Thus, ascending noradrenergic afferents may be involved in more complex aspects of cognitive performance (i.e., working memory) possibly via newly generated progenitors in the hippocampus.
authors.affiliation: B.R.A.I.N. Laboratory for Neurogenesis and Repair, Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Marino
authors.initials: M
authors.lastname: Coradazzi
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, Catania, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Gulino
authors.affiliation: B.R.A.I.N. Laboratory for Neurogenesis and Repair, Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fieramosca
authors.affiliation: B.R.A.I.N. Laboratory for Neurogenesis and Repair, Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Lucia Verga
authors.initials: LV
authors.lastname: Falzacappa
authors.affiliation: B.R.A.I.N. Laboratory for Neurogenesis and Repair, Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Riggi
authors.affiliation: B.R.A.I.N. Laboratory for Neurogenesis and Repair, Department of Life Sciences, University of Trieste, Trieste, Italy. Electronic address: gleanza@units.it.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Leanza
mesh_terms: D059331:Adrenergic Neurons / Q000473:pathology* / Q000502:physiology*; D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology*; D055495:Neurogenesis; D009638:Norepinephrine / Q000172:deficiency* / Q000502:physiology*; D017207:Rats, Sprague-Dawley
chemical_list: D009638:Norepinephrine
keywords: Adult neural progenitor cells; Alzheimer's disease; Immunotoxin; Noradrenaline; Rat; Working memory