title: Age-related changes of hippocampal synaptic plasticity in AβPP-null mice are restored by NGF through p75NTR.
abstract: Amyloid-β protein precursor (AβPP) is a ubiquitous protein found in all cell types, suggesting basic and yet important roles, which still remain to be fully elucidated. Loss of function of AβPP has been linked to abnormal neuronal morphology and synaptic function within the hippocampus and alterations in spatial learning, suggesting a neurotrophic role for this protein. Besides AβPP, nerve growth factor (NGF) and other neurotrophins have also been shown to finely modulate neuronal excitability, synaptic plasticity, and cognitive functions. In addition, recent data support the hypothesis of a functional interconnection between AβPP and NGF pathway. Here, we demonstrated that loss of AβPP function, leading to progressive decrease of choline acetyltransferase expression in the septum, correlates with age-related impairment of long-term potentiation (LTP) in the dentate gyrus. We next addressed whether impaired hippocampal plasticity in AβPP-null mice can be restored upon NGF treatment. Notably, NGF, as well as Pro-NGF, can fully revert LTP deficits in AβPP-null mice through p75NTR and JNK pathway activation. Overall the present study may unveil a new mechanism by which, in the absence of AβPP, NGF treatment may preferentially direct p75-neurotrophin-dependent JNK activation toward regeneration and plasticity in functionally relevant brain circuits.
authors.affiliation: Institute of Cellular Biology and Neurobiology, National Council of Research of Rome, Rome, Italy.
authors.forename: Luca Rosario
authors.initials: LR
authors.lastname: La Rosa
authors.forename: Carmela
authors.initials: C
authors.lastname: Matrone
authors.forename: Caterina
authors.initials: C
authors.lastname: Ferraina
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Panico
authors.forename: Silvia
authors.initials: S
authors.lastname: Piccirilli
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Di Certo
authors.forename: Georgios
authors.initials: G
authors.lastname: Strimpakos
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.forename: Pietro
authors.initials: P
authors.lastname: Calissano
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics*; D020917:Receptor, trkA / Q000172:deficiency / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020932:Nerve Growth Factor; D020917:Receptor, trkA