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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BDIVRatsynucleinopathy MODEL: controlIAGP compared to BDIV-Myo5a/StcRrrcRGD 
BDIV-Myo5a/StcRrrcRatsynucleinopathy MODEL: spontaneousIAGP compared to control BD-IVRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Myo5aRatnegative regulation of synaptic transmission, glutamatergic  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BDIV-Myo5a/StcRrrcRatabnormal motor capabilities/coordination/movement  IAGP compared to control BD-IVRGD 
BDIV-Myo5a/StcRrrcRatabnormal synaptic dopamine release inducedIAGPneuromodulationcompared to control BD-IVRGD 
BDIV-Myo5a/StcRrrcRatalpha-synuclein inclusion body  IAGP in striatum more ...RGD 
BDIV-Myo5a/StcRrrcRatdecreased dopaminergic neuron number  IAGP in substantia nigra pars compacta and compared to control BD-IVRGD 
BDIV-Myo5a/StcRrrcRatdecreased excitatory postsynaptic current amplitude inducedIAGPdirect electrical nerve stimulationcompared to control BD-IVRGD 
BDIV-Myo5a/StcRrrcRatdecreased synaptic glutamate release inducedIAGPdirect electrical nerve stimulationcompared to control BD-IVRGD 
BDIV-Myo5a/StcRrrcRatneurodegeneration  IAGP compared to control BD-IVRGD 
BDIV-Myo5a/StcRrrcRatvariegated coat color  IAGP compared to control BD-IVRGD 
Objects Annotated

Genes (Rattus norvegicus)
Myo5a  (myosin VA)

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


Additional Information