Age-Related Changes of Hippocampal Synaptic Plasticity in A beta PP-Null Mice are Restored by NGF Through p75(NTR)

作者：La Rosa Luca Rosario; Matrone Carmela; Ferraina Caterina; Panico Maria Beatrice; Piccirilli Silvia; Di Certo Maria Grazia; Strimpakos Georgios; Mercuri Nicola Biagio; Calissano Pietro; D' Amelio Marcello; Nistico Robert^*

来源：Journal of Alzheimer's Disease, 2013, 33(1): 265-272.

DOI：10.3233/JAD-2012-112108

• Amyloid-beta protein precursor
• c-jun N-terminal kinase
• dentate gyrus
• long-term potentiation
• nerve growth factor
• p75(NTR)

Amyloid-beta protein precursor (A beta PP) 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 A beta PP 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 A beta PP, 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 A beta PP and NGF pathway. Here, we demonstrated that loss of A beta PP 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 A beta PP-null mice can be restored upon NGF treatment. Notably, NGF, as well as Pro-NGF, can fully revert LTP deficits in A beta PP-null mice through p75(NTR) and JNK pathway activation. Overall the present study may unveil a new mechanism by which, in the absence of A beta PP, NGF treatment may preferentially direct p75-neurotrophin-dependent JNK activation toward regeneration and plasticity in functionally relevant brain circuits.

• 出版日期2013