Fig. 6

Caspase-resistant Beclin 1 rescues neurodegeneration in vivo. a, b Adult mice were lesioned with Kainic acid three weeks post stereotaxic delivery of wild-type full length (FL) or caspase-resistant (CR)-beclin-AAV into the hippocampus and Control-AAV into the contralateral hemisphere. a Comparison of neuronal CR-Beclin 1 to control-AAV expression. Neuronal injury was assessed by Nissl staining (top panel) and Calbindin immunostaining (middle panel). Microglial activation was assessed by CD68 immunostaining (lower panel). Representative hippocampal images from adjacent sections of one animal expressing CR-Beclin (right hemisphere) and control (left hemisphere) (scale bar 200 μm). b Direct comparison of FL-Beclin 1 to CR-Beclin 1 in Kainic acid lesioned mice. FL-beclin-AAV and CR-beclin-AAV were stereotaxically injected into contralateral hippocampi of the same animal. Neuronal injury was assessed by Nissls staining (top panel) and Calbindin immunostaining (middle panel). Microglial activation was assessed using CD68 immunostaining (lower panel). Representative hippocampal images from adjacent sections (scale bar: 200 μm). c-e Quantification of Nissl staining (c), Calbindin immunostaining (d) and CD68 immunostaining (e) expressed as percentage area covered by staining in the CA1 region of the hippocampus (n = 8–12 mice/group; 4–5 sections per mouse brain). Data expressed as mean + SEM; *p < 0.05; compared by unpaired Student’s t-test and one-way ANOVA with a Tukey’s post test for multiple comparisons