Study of mGlu3R function in primary glial cultures from transgenic Alzheimer’s mice

EUGENIA OLIVERA; PILAR GARAVENTA; ALBANY SÁEZ; ANA CLARA ROMERO; FEDERICO LÓPEZ COUSELO; LILA CARNIGLIA; CARLA CARUSO; JUAN BEAUQUIS; FLAVIA SARAVIA; MERCEDES LASAGA; DANIELA DURAND

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2023

Sociedad Argentina de Investigación Clínica

Our group has demonstrated that the subtype 3 metabotropic glutamate receptor (mGlu3R) expressed in astrocytes exerts neuroprotective functions and promotes the non-amyloidogenic cleavage of APP. In turn, we described the presence of the splicing variant mGlu3Δ4 in the hippocampus of PDAPP-J20 murine AD model, where mGlu3R levels progressively decreased with age, while Δ4 levels increased prematurely. In vitro results suggested that mGlu3Δ4 could act as a negative regulator of mGlu3R.Here, we used glial cell cultures from PDAPP-J20 mice to test if the results observed in hippocampi were reflected on the glia. These in vitro assays would make it possible to test the effect of mGlu3R agonists as well. To achieve this, cultures of 1-month-old transgenic (Tg) and non-transgenic (Ntg) mice were performed using a Percoll gradient. We obtained glia-enriched cultures with a high proportion of ALDH1L1+ astrocytes (64.5 ± 7.03%), microglia CX3CR1+, and a low proportion of neurons (7.6 ± 2.8%). Surprisingly, only 2.16 ± 0.08% of the astrocytes were found to be GFAP+.We analyzed the expression of glial proteins implicated in AD. Western blot analysis showed a significant decrease in mGlu3R levels in Tg cultures (p