Age-related changes of hippocampal synaptic plasticity in aβPP-null mice are restored by ngf through p75NTR

Luca Rosario La Rosa, Carmela Matrone, Caterina Ferraina, Maria Beatrice Panico, Silvia Piccirilli, Maria Grazia Di Certo, Georgios Strimpakos, Nicola Biagio Mercuri, Pietro Calissano, Marcello D'amelio, Robert Nistic̀o

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)265-272
Number of pages8
JournalJournal of Alzheimer's Disease
Volume33
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Amyloid-β protein precursor
  • c-jun N-terminal kinase
  • dentate gyrus
  • long-term potentiation
  • nerve growth factor
  • p75

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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