mGlu3R expression and effect on antioxidant parameters during astrocyte aging and in an Alzheimer?s disease model

TURATI, JUAN; DELIA RAMÍREZ; CARNIGLIA, LILA; JULIETA SABA; CARLA CARUSO; JUAN, BEAUQUIS; FLAVIA, SARAVIA; DANIELA DURAND; MERCEDES LASAGA

Berlin

Congreso; FENS Forum of Neuroscience; 2018

FENS Forum of Neuroscience

Aims: Astroglial subtype 3 metabotropic glutamate receptors (mGlu3R) present protective actions against neurotoxic agents and we demonstrated that mGlu3R activation promotes the non-amyloidogenic cleavage of amyloid precursor protein in astrocytes, suggesting a role for these receptors in Alzheimer?s disease (AD). Here we explored its role in normal aging and aging-related oxidative stress, Methods: Astrocyte aging was modeled in vitro in 9-week cultures, and compared to 3-week cultures, both treated with the mGlu3R agonist LY379268. ROS and Glutathione was measured by fluorescence intensity; SOD activity was determined by spectrophotometry; wNrf2 was quantified by Western Blot. In hippocampus from wild-type (wt) or transgenic (Tg) mice (PDAPP-J20 model of AD) of 5, 9, 14 and 20 months (m) old, mGlu3R and Serine Racemase (SR) expression were determined by RT-qPCR. Results: In vitro astrocyte aging resulted in increased Nrf2 expression, ROS production and glutathione levels, whereas both viability and SOD activity significantly decreased. Neither acute (24h) nor prolonged treatment (1 week) with LY379268 had any effect on antioxidant parameters, although acute exposure to LY379268 significantly increased SOD activity. mGluR3 levels were higher in 9m-wt mice compared with 5m-wt mice, whereas this ratio was inversed in Tg animals and mGlu3R protein levels decreased with age in Tg mice. Expression of SR also decreased with age in Tg mice but not in wt littermates. Conclusion: mGlu3R and Serine Racemase expression is differentially modulated