V-12
Cellular and Molecular Neurobiology
mGlu3R and GCPII Alterations Across Alzheimer’s and Huntington’s Disease Models
José Presta1,2, Gisela Novack1,2, María Friser Frederiksen1,2, Eugenia Olivera1,2, Constanza Lipari2,6, Albany Sáez1,2, Mónica Mezmezian3, Gustavo Sevlever3, Flavia Saravia4,5, Mercedes Lasaga1,2, Carla Caruso1,2, Daniela Durand1,2
1. Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina.
2. CONICET - Universidad de Buenos Aires. Instituto de Investigaciones Biomédicas (INBIOMED). Buenos Aires, Argentina.
3. Laboratorio de Neuropatología, Banco de Cerebros, Fleni, Buenos Aires, Argentina.
4. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
5. Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
6. Universidad de Buenos Aires, Facultad de Psicología. Cátedra Única Psicofarmacología. Buenos Aires, Argentina.
Presenting Author:
jopresta@uade.edu.ar
Metabotropic glutamate receptor 3 (mGlu3R) is involved in neuroprotective mechanisms and is activated by NAAG, whose availability is regulated by the enzyme GCPII. We aimed to evaluate whether alterations in this system constitute a shared pathophysiological mechanism among neurodegenerative diseases of different origins and to assess the influence of the APOE4 genotype on the expression of its components. mGlu3R and GCPII expression was analyzed in mouse models of Alzheimer’s disease (PDAPP-J20) and Huntington’s disease (zQ175), as well as GCPII in human samples and CSF data obtained from AD Workbench. In zQ175 mice, mGlu3R showed a trend toward decreased levels in transgenic animals compared with controls (p=0.073), consistent with previously published results in PDAPP-J20. For GCPII, Western blots from both models showed bands at molecular weights different from those expected and no significant differences between WT and Tg animals. No clear diagnosis-associated pattern was observed in human samples. Protein abundance data obtained using SOMAmers, expressed as RFU, were analyzed by one-way ANOVA. In CSF samples from patients with Alzheimer’s disease, GCPII levels showed no significant differences among individuals with no APOE4 allele, one copy, or two copies of the allele (F=0.524; p=0.593). The reduction in mGlu3R levels may represent shared pathophysiological mechanism between AD and HD, whereas variations in GCPII do not appear to be associated with these pathologies.
