Cellular and Molecular Neurobiology
Author: Pilar Garaventa | Email: piluxgaraventa@gmail.com
Pilar Garaventa1°, Eugenia Olivera1°, Albany Sáez1°, Ana Clara Romero1°, Juan Beauquis2°3°, Carla Caruso1°, Flavia Saravia2°3°, Mercedes Lasaga1°, Daniela Durand1°
1° Instituto de Investigaciones Biomédicas (INBIOMED) UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires
2° Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires
3° Instituto de Biología y Medicina Experimental, CONICET
mGlu receptors, particularly the mGlu3R subtype, have neuroprotective functions in various pathologies through glia. The splicing variant mGlu3Δ4 could act as a negative modulator of mGlu3R, according to our previous studies.
It has been postulated that synaptic pruning would be reactivated at the onset of AD, leading to synaptic loss. The complement system has been associated with this process, and synapses marked with C1q can be phagocytosed by glia expressing the complement receptor.
The aim of this study is to investigate the role of mGlu3R in glia-mediated synaptic elimination in the murine model PDAPP-J20. To this end, primary glial cultures were prepared and synaptosomes isolated from wild-type (Ntg) and transgenic (Tg) mice.
The Tg cultures showed increased immunofluorescence for C1q (p<0.05) and decreased levels of mGlu3R (p<0.05), which co-localized in glial membranes. On the other hand, Tg synaptosomes expressed higher levels of mGlu3R, mGlu3Δ4, and C1q (p<0.05). Additionally, engulfment assays were performed using glial cultures treated or not with the mGlu3R agonist, LY379268, which were then incubated with Ntg or Tg synaptosomes. We observed that glia preferentially engulfed Tg synaptosomes, whereas the effect of LY was variable. In conclusion, alterations in mGlu3R and mGlu3Δ4 levels were observed in the AD model, both in glial cells and synaptic terminals. A possible relationship between mGlu3R, C1q, and synaptic elimination in AD was also noted.