2016
DOI: 10.1002/mds.26620
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Early synaptic dysfunction in Parkinson's disease: Insights from animal models

Abstract: The appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and bot… Show more

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Cited by 138 publications
(105 citation statements)
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References 119 publications
(279 reference statements)
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“…Rodent models display many of the clinical features of PD such as the loss of dopaminergic neurons (Meredith and Rademacher, 2011; Thiele et al, 2012; Torres and Dunnett, 2012), neurochemical changes in dopamine transmission and signaling, motor dysfunction, and non-motor symptoms including cognitive decline, autonomic dysfunction, depression, and hyposmia (Taylor et al, 2010; Schirinzi et al, 2016). However, these models do not mimic some important pathological hallmarks of the disease (Fleming and Chesselet, 2006; Visanji et al, 2016) such as the gradual neurodegenerative process, gross morphological abnormalities and overt motor alterations (Yue and Lachenmayer, 2011; Ribeiro et al, 2013; Schirinzi et al, 2016). Moreover, gene editing techniques in rodents involve complex experimental design, significant time investment and considerable expense.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Rodent models display many of the clinical features of PD such as the loss of dopaminergic neurons (Meredith and Rademacher, 2011; Thiele et al, 2012; Torres and Dunnett, 2012), neurochemical changes in dopamine transmission and signaling, motor dysfunction, and non-motor symptoms including cognitive decline, autonomic dysfunction, depression, and hyposmia (Taylor et al, 2010; Schirinzi et al, 2016). However, these models do not mimic some important pathological hallmarks of the disease (Fleming and Chesselet, 2006; Visanji et al, 2016) such as the gradual neurodegenerative process, gross morphological abnormalities and overt motor alterations (Yue and Lachenmayer, 2011; Ribeiro et al, 2013; Schirinzi et al, 2016). Moreover, gene editing techniques in rodents involve complex experimental design, significant time investment and considerable expense.…”
Section: Introductionmentioning
confidence: 99%
“…In addition, environmental exposure to paraquat is a risk factor for PD; paraquat administration increases α-synuclein levels and α-synuclein-positive inclusion bodies in substantia nigra neurons (Manning-Bog et al, 2002). A major drawback of toxin-induced models is that acutely induced neurodegeneration investigates a phase of PD when nearly 70–80% of dopaminergic neurons are already lost, thus lacking the age-dependent progressive lesions and Lewy bodies that are typical of human patients (Blandini and Armentero, 2012; Schirinzi et al, 2016). …”
Section: Introductionmentioning
confidence: 99%
“…The pathophysiology of LIDs has classically been based on dopamine‐synaptic and receptor‐mediated mechanisms . In addition to abnormal activation of denervated dopamine receptors by l ‐dopa, changes in receptor density, membrane internalization, and coupling of dopamine D1 receptors as well as reduced dopaminergic synaptic plasticity have been profusely ascertained and discussed as the origin of LIDs …”
mentioning
confidence: 99%
“…Indeed, striatal dopamine, deriving from SNpc, is critical for the physiological occurrence of synaptic plasticity, a biological phenomenon by which corticostriatal synapses bidirectionally change their strength (Long-term potentiation or LTP and Long-term depression or LTD). Modulation of LTD and LTP plays a fundamental role for a correct motor control, and accordingly, abnormal plasticity is observed in a number of experimental models of PD [5]. The authors report that in heterozygous PINK1 knockout mice, the subtle plasticity impairment may be significantly worsened by the exposure to environmental stressors such as pesticides [6], that are well-established environmental toxins, capable of inducing nigral degeneration [1, 6].…”
mentioning
confidence: 99%