Glial cell reactivity drives cognitive decline in LDLr‐/‐ mice: experimental evidences

Background Familial hypercholesterolemia (FH) is a clinical condition characterized by increased plasma cholesterol levels, due to mutation in the gene encoding low-density lipoprotein receptor (LDLr) cells [Brown and Goldstein, 1984]. Importantly, evidence indicates that FH negatively affects cognition favors development of neuropathologies [Ariza et al., 2016; Zambón al, 2010], however, mechanisms behind this relationship are still not fully understood. In study we aimed investigate role glial cell reactivity on cognitive deficits related FH, as well possible neuroprotective effect pharmacological inhibitor microglial activation. Method Firstly, male 3-months-old 14-months-old C57BL/6 wild-type LDLr knockout mice (LDLr-/-) brains were prepared for evaluation morphology immunofluorescence. addition, mice’s hippocampus was removed measure immune content synaptic tight-junctions proteins. Moreover, female 6-months-old LDLr-/- treated with minocycline (50 mg/kg) or vehicle (saline) four weeks. Afterwards, submitted behavioral tests. Result Middle-aged (14-months-old) exhibited microgliosis hippocampus, which correlated morphological change astrocytes same brain region. Also, middle-aged presented reduction synaptophysin-1 hippocampus. young adult (3-months-old) reduced PSD95 Finally, administration ameliorated performance hypercholesterolemic hippocampal-dependent memory tasks, without modifying their locomotor activity metabolic parameters. Conclusion Taken together, our results demonstrated alters reactivity, associated changes proteins modulation mice, suggesting key event HF-related deficits.