title: Nerve growth factor and autophagy: effect of nasal anti-NGF-antibodies administration on Ambra1 and Beclin-1 expression in rat brain.
abstract: Nerve growth factor (NGF) exerts protective actions in the healthy and diseased nervous system. Intranasal administration is a suitable and safe strategy to deliver NGF to CNS neurons. We investigated whether nasal anti-NGF-antibody (ANA) administration affects neuronal autophagy, in view of its putative regulatory role in this process. We focused on olfactory bulbs (OB), neocortex (Cx), hippocampus (HF) and septal complex (SC), known to be NGF-responsive and autophagically active. Our combined molecular/morphological results demonstrate that intranasally administered ANA reaches brain NGF-target neurons and lowers the levels of endogenous NGF and its receptors. Treatment also affects - in a brain region-dependent manner - the expression of the autophagic proteins Beclin-1 and Ambra1, as well as that of proteins belonging to the Bcl2 family, namely Bax and Bcl-2, reflecting apoptotic dysregulation. This study provides a nongenetically modified, NGF-defective animal model, representing a suitable tool to investigate novel properties of the neurotrophin, especially in relation to autophagy.
authors.affiliation: a National Research Council (CNR), Institute of Cell Biology & Neurobiology , Rome , Italy and.|b Department of Science , LIME, University Roma Tre , Rome , Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Rosso
authors.affiliation: b Department of Science , LIME, University Roma Tre , Rome , Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moreno
authors.affiliation: b Department of Science , LIME, University Roma Tre , Rome , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Fracassi
authors.affiliation: a National Research Council (CNR), Institute of Cell Biology & Neurobiology , Rome , Italy and.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Rocco
authors.affiliation: a National Research Council (CNR), Institute of Cell Biology & Neurobiology , Rome , Italy and.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D045744:Cell Line, Tumor; D006624:Hippocampus / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism; D020932:Nerve Growth Factor / Q000276:immunology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000595495:Ambra1 protein, rat; D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; C494828:Bax protein, rat; D000071186:Beclin-1; C512829:Becn1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D017475:Receptors, Nerve Growth Factor; D051028:bcl-2-Associated X Protein; D020932:Nerve Growth Factor
keywords: Ambra1; Beclin-1; Nerve growth factor (NGF); anti-NGF-antibodies (ANA); autophagy; nasal administration