METABOTROPIC GLUTAMATE RECEPTOR (mGlu3R) SPLICING VARIANTS IN AGING AND ALZHEIMER´S DISEASE

RAMIREZ, DELIA; LÓPEZ COUSELO, FEDERICO; SARAVIA, FLAVIA; RUDI, MARIA JULIETA; CARNIGLIA, LILA; CARUSO, CARLA; LASAGA, MERCEDES; TURATI, JUAN; SABA, JULIETA; BEAUQUIS, JUAN; DURAND, DANIELA

Oporto

Congreso; XIV European Meeting on Glial Cells in Health and Disease; 2019

GLIA

Subtype 3 metabotropic glutamate receptors (mGlu3R) promote several neuroprotective effects, especially in glial cells. We have previously demonstrated that mGlu3R activation in astrocytes promotes the non-amyloidogenic cleavage of amyloid precursor protein and induces the release of neurotrophin sAPPα, whereas it also increases Aβ uptake by astrocytes, which consequently improves neuron survival in co-culture systems. It is known that a truncated version of the receptor, called mGlu3Δ4R, which lacks the transmembrane domain and has been linked to a schizophrenic status, acts as a negative modulator of mGlu3R. In fact, mGlu3Δ4R is able to interact with canonical mGlu3R thereby inhibiting the functional mGlu3R homodimerization. We aimed to study whether mGlu3R alternative splicing could also be associated with Alzheimer?s disease (AD) progression in the AD mice model PDAPP-J20 and whether Aβ could favor the mentioned splicing in astrocytes. Our results from western blot analysis show that mGlu3R protein levels remain stable at 5, 9, and 14 months old in non-transgenic (NTg) mice hippocampus, whereas levels of both monomeric and dimeric forms of mGlu3R progressively decrease with age in PDAPP-J20 (Tg) animals (p