The presence of α-synuclein (α-syn) in Lewy bodies and Lewy neurites is an important characteristic of the neurodegenerative processes of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons in Parkinson's disease (PD) and other synucleinopathies. Here we report that Berlin-Druckrey rats carrying a spontaneous mutation in the 3' untranslated region of α-syn mRNA (m/m rats) display a marked accumulation of α-syn in the mesencephalic area, striatum and frontal cortex, accompanied to severe dysfunctions in the dorsolateral striatum. Despite a small reduction in the number of SNpc and ventral tegmental area DAergic cells, the surviving dopaminergic neurons of the m/m rats do not show clear-cut alterations of the spontaneous and evoked firing activity, DA responses and somatic amphetamine-induced firing inhibition. Interestingly, mutant DAergic neurons display diminished whole-cell Ih conductance and a reduced frequency of spontaneous excitatory synaptic currents. By contrast, m/m rats show a severe impairment of DA and glutamate release in the dorsolateral striatum, as revealed by amperometric measure of DA currents and by electrophysiological recordings of glutamatergic synaptic events in striatal medium spiny neurons. These functional impairments are paralleled by a decreased expression of the DA transporter and VGluT1 proteins in the same area. Thus, together with α-syn overload in the mesencephalic region, striatum and frontal cortex, the main functional alterations occur in the DAergic and glutamatergic terminals in the dorsal striatum of the m/m rats.

Guatteo, E., Rizzo, F.r., Federici, M., Cordella, A., Ledonne, A., Latini, L., et al. (2017). Functional alterations of the dopaminergic and glutamatergic systems in spontaneous α-synuclein overexpressing rats. EXPERIMENTAL NEUROLOGY, 287(Pt 1), 21-33 [10.1016/j.expneurol.2016.10.009].

Functional alterations of the dopaminergic and glutamatergic systems in spontaneous α-synuclein overexpressing rats

Rizzo F. R.;Federici M.;Cordella A.;Ledonne A.;Nobili A.;D'Amelio M.;Mercuri N. B.
2017-01-01

Abstract

The presence of α-synuclein (α-syn) in Lewy bodies and Lewy neurites is an important characteristic of the neurodegenerative processes of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons in Parkinson's disease (PD) and other synucleinopathies. Here we report that Berlin-Druckrey rats carrying a spontaneous mutation in the 3' untranslated region of α-syn mRNA (m/m rats) display a marked accumulation of α-syn in the mesencephalic area, striatum and frontal cortex, accompanied to severe dysfunctions in the dorsolateral striatum. Despite a small reduction in the number of SNpc and ventral tegmental area DAergic cells, the surviving dopaminergic neurons of the m/m rats do not show clear-cut alterations of the spontaneous and evoked firing activity, DA responses and somatic amphetamine-induced firing inhibition. Interestingly, mutant DAergic neurons display diminished whole-cell Ih conductance and a reduced frequency of spontaneous excitatory synaptic currents. By contrast, m/m rats show a severe impairment of DA and glutamate release in the dorsolateral striatum, as revealed by amperometric measure of DA currents and by electrophysiological recordings of glutamatergic synaptic events in striatal medium spiny neurons. These functional impairments are paralleled by a decreased expression of the DA transporter and VGluT1 proteins in the same area. Thus, together with α-syn overload in the mesencephalic region, striatum and frontal cortex, the main functional alterations occur in the DAergic and glutamatergic terminals in the dorsal striatum of the m/m rats.
2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Amperometry
DAergic terminals
Dopaminergic neurons
Dorsal striatum
Electrophysiology
Glutamatergic terminals
Lewy bodies dementia
Mutated rats
Parkinson's disease
Substantia nigra
Synaptic release
α-synuclein
6-Cyano-7-nitroquinoxaline-2,3-dione
Animals
Animals, Newborn
Bicuculline
Cell Count
Dopamine
Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Excitatory Amino Acid Antagonists
GABA Antagonists
GABA-B Receptor Agonists
Glutamic Acid
In Vitro Techniques
Membrane Potentials
Mesencephalon
Patch-Clamp Techniques
Picrotoxin
Rats
Synaptic Potentials
Vesicular Glutamate Transport Protein 1
Vesicular Glutamate Transport Protein 2
alpha-Synuclein
Guatteo, E., Rizzo, F.r., Federici, M., Cordella, A., Ledonne, A., Latini, L., et al. (2017). Functional alterations of the dopaminergic and glutamatergic systems in spontaneous α-synuclein overexpressing rats. EXPERIMENTAL NEUROLOGY, 287(Pt 1), 21-33 [10.1016/j.expneurol.2016.10.009].
Guatteo, E; Rizzo, Fr; Federici, M; Cordella, A; Ledonne, A; Latini, L; Nobili, A; Viscomi, Mt; Biamonte, F; Landrock, Kk; Martini, A; Aversa, D; Sche...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/262618
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