Down-regulation of mGLuR5 in the CA3 region via shRNA lentivirus delivery is protective. A. Schematic representation of lentivirus expressing either control vector or sh mGLuR5 that was injected unilaterally in the CA3 of the hippocampus. B. Representative photomicrographs and C image analysis of sections from mice injected with LV-control and immunoreacted with mGluR5, α-syn and MAP 2. Injecting LV-control had no effect on either non-tg or tg mice and was comparable to the initial characterization of these mice in which levels of mGLuR5, α-syn, and MAP 2-ir. D. Representative photomicrographs and E. image analysis revealed that injection of the LV-sh mGluR5 resulted in a significant reduction in mGluR5 in the neuronal cell bodies and dendrites in the CA3 of the hippocampus in the non-tg and tg lines. While α-syn remained unaffected by LV-sh mGluR5 with α-syn increased in α-syn and α-syn/APP tg mice, levels of MAP 2-ir were improved in the CA3 region. * = p-value < 0.05 and ** = p-value < 0.01 by one-way ANOVA and Dunnett’s post hoc analysis compared to non-tg mice. # = p-value < 0.05 by one-way ANOVA and Tukey-Kramer post hoc analysis when compared to α-syn/APP tg mice. For each analysis, N = 6 (3–4 months old) mice from each line were utilized.