RGD Reference Report - Functional alterations of the dopaminergic and glutamatergic systems in spontaneous α-synuclein overexpressing rats. - Rat Genome Database

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

Authors: Guatteo, Ezia  Rizzo, Francesca Romana  Federici, Mauro  Cordella, Alberto  Ledonne, Ada  Latini, Laura  Nobili, Annalisa  Viscomi, Maria Teresa  Biamonte, Filippo  Landrock, Kerstin K  Martini, Alessandro  Aversa, Daniela  Schepisi, Chiara  D'Amelio, Marcello  Berretta, Nicola  Mercuri, Nicola B 
Citation: Guatteo E, etal., Exp Neurol. 2017 Jan;287(Pt 1):21-33. doi: 10.1016/j.expneurol.2016.10.009. Epub 2016 Oct 20.
RGD ID: 41412185
Pubmed: PMID:27771352   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2016.10.009   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
synucleinopathy MODEL: controlIAGP 41412185compared to BDIV-Myo5a/StcRrrcRGD 
synucleinopathy MODEL: spontaneousIAGP 41412185compared to control BD-IVRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of synaptic transmission, glutamatergic  IMP 41412185 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal motor capabilities/coordination/movement  IAGP 41412185compared to control BD-IVRGD 
abnormal synaptic dopamine release inducedIAGPneuromodulation41412185compared to control BD-IVRGD 
alpha-synuclein inclusion body  IAGP 41412185in striatum more ...RGD 
decreased dopaminergic neuron number  IAGP 41412185in substantia nigra pars compacta and compared to control BD-IVRGD 
decreased excitatory postsynaptic current amplitude inducedIAGPdirect electrical nerve stimulation41412185compared to control BD-IVRGD 
decreased synaptic glutamate release inducedIAGPdirect electrical nerve stimulation41412185compared to control BD-IVRGD 
neurodegeneration  IAGP 41412185compared to control BD-IVRGD 
variegated coat color  IAGP 41412185compared to control BD-IVRGD 
Objects Annotated

Genes (Rattus norvegicus)
Myo5a  (myosin VA)

Strains
BDIV  (NA)
BDIV-Myo5a/StcRrrc  (NA)


Additional Information