Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease.
Glutamatergic pathways play a key role in the functional organization of neuronal circuits involved in Parkinson disease (PD). Recently, three vesicular glutamate transporters (VGLUT1-3) were identified. VGLUT1 and VGLUT2 are responsible for the uploading of glutamate into synaptic vesicles and are the first specific markers of glutamatergic neurons available. Here, we analyzed the expression of VGLUT1 and VGLUT2 in autopsy tissues of PD patients and matched controls using Western blot and immunoautoradiography. VGLUT1 and VGLUT2 expression was increased in the Parkinsonian putamen by 24% and 29%, respectively (p<0.01). In contrast, only VGLUT1 was dramatically decreased in the prefrontal and temporal cortex of PD patients (approximately 50%, p<0.01 and p<0.001, respectively). These findings demonstrate the existence of profound alterations of glutamatergic transmission in PD, which are likely to contribute to the motor and cognitive impairments associated with the disease, and should thus be taken into account in the treatment of PD.
INSERM U513, Faculté de Médecine, Université Paris XII, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
Alireza
A
Kashani
Catalina
C
Betancur
Bruno
B
Giros
Etienne
E
Hirsch
Salah
S
El Mestikawy
D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D011180:Postmortem Changes; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*
D009419:Nerve Tissue Proteins; C493476:SLC17A6 protein, human; C493464:SLC17A7 protein, human; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2