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.

La Rosa, L., Matrone, C., Ferraina, C., Panico, M., Piccirilli, S., Di Certo, M., et al. (2013). Age-related changes of hippocampal synaptic plasticity in AβPP-null mice are restored by NGF through p75NTR. JOURNAL OF ALZHEIMER'S DISEASE, 33(1), 265-272 [10.3233/JAD-2012-112108].

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

PICCIRILLI, SILVIA;MERCURI, NICOLA BIAGIO;CALISSANO, PIETRO;NISTICO', ROBERT GIOVANNI
2013-01-01

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.
2013
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
English
Animals; Synapses; Hippocampus; Aging; Mice; Nerve Growth Factor; Mice, Knockout; Mice, 129 Strain; MAP Kinase Signaling System; Excitatory Postsynaptic Potentials; Receptor, trkA; Mice, Inbred C57BL; Neuronal Plasticity; Receptors, Nerve Growth Factor; Long-Term Potentiation; Signal Transduction; Amyloid beta-Protein Precursor; Male
La Rosa, L., Matrone, C., Ferraina, C., Panico, M., Piccirilli, S., Di Certo, M., et al. (2013). Age-related changes of hippocampal synaptic plasticity in AβPP-null mice are restored by NGF through p75NTR. JOURNAL OF ALZHEIMER'S DISEASE, 33(1), 265-272 [10.3233/JAD-2012-112108].
La Rosa, L; Matrone, C; Ferraina, C; Panico, M; Piccirilli, S; Di Certo, M; Strimpakos, G; Mercuri, Nb; Calissano, P; D'Amelio, M; Nistico', Rg...espandi
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Descrizione: Age-related changes of hippocampal synaptic plasticity in AβPP-null mice are restored by NGF through p75NTR
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/101305
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