title: Subtle alterations of excitatory transmission are linked to presynaptic changes in the hippocampus of PINK1-deficient mice.
abstract: Homozygous or heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene have been linked to early-onset Parkinson's disease (PD). Several neurophysiological studies have demonstrated alterations in striatal synaptic plasticity along with impaired dopamine release in PINK1-deficient mice. Using electrophysiological methods, here we show that PINK1 loss of function causes a progressive increase of spontaneous glutamate-mediated synaptic events in the hippocampus, without influencing long-term potentiation. Moreover, fluorescence analysis reveals increased neurotrasmitter release although our biochemical results failed to detect which presynaptic proteins might be engaged. This study provides a novel role for PINK1 beyond the physiology of nigrostriatal dopaminergic circuit. Specifically, PINK1 might contribute to preserve synaptic function and glutamatergic homeostasis in the hippocampus, a brain region underlying cognition. The subtle changes in excitatory transmission here observed might be a pathogenic precursor to excitotoxic neurodegeneration and cognitive decline often observed in PD. Using electrophysiological and fluorescence techniques, we demonstrate that lack of PINK1 causes increased excitatory transmission and neurotransmitter release in the hippocampus, which might lead to the cognitive decline often observed in Parkinson's disease.
authors: EBRI-European Brain Research Institute, Rome, Italy.|Casa Cura Policlinico, Milan, Italy.
authors: Marco
authors: M
authors: Feligioni
authors: EBRI-European Brain Research Institute, Rome, Italy.
authors: Dalila
authors: D
authors: Mango
authors: EBRI-European Brain Research Institute, Rome, Italy.
authors: Sonia
authors: S
authors: Piccinin
authors: University of Rome "Tor Vergata", Rome, Italy.
authors: Paola
authors: P
authors: Imbriani
authors: EBRI-European Brain Research Institute, Rome, Italy.
authors: Filomena
authors: F
authors: Iannuzzi
authors: Sapienza University of Rome, Rome, Italy.
authors: Alessandra
authors: A
authors: Caruso
authors: Sapienza University of Rome, Rome, Italy.
authors: Francesca
authors: F
authors: De Angelis
authors: IRCSS "C. Mondino", National Neurological Institute, Pavia, Italy.
authors: Fabio
authors: F
authors: Blandini
authors: University of Rome "Tor Vergata", Rome, Italy.|IRCSS Santa Lucia Foundation, Rome, Italy.
authors: Nicola B
authors: NB
authors: Mercuri
authors: University of Rome "Tor Vergata", Rome, Italy.
authors: Antonio
authors: A
authors: Pisani
authors: EBRI-European Brain Research Institute, Rome, Italy.|University of Rome "Tor Vergata", Rome, Italy.
authors: Robert
authors: R
authors: Nisticò
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D004298:Dopamine; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase
keywords: Parkinson's disease; electrophysiology; hippocampus; long-term potentiation; neurotransmitter release; synaptic transmission