Caspase inhibition in neuroinflammation induced by soluble β amyloid monomer, protects cells from abnormal survival and proliferation, via attenuation of NFқB activity

Evidence suggests that neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. Elucidating this question may be helpful in management of neurodegenerative diseases. Since TNF-α is able to induce apoptosis as well as increased viability of the cells by activation of caspases or NF-kB, respectively, the question is what will happen if the balance between the two pathways is disturbed by inhibition of apoptosis. In this study, we used β–amyloid peptide (soluble Aβ monomer) injection into the Wistar male rat prefrontal cortex for induction of neuroinflammation in the hippocampus. Levels of TNF-α and caspase-3 were determined via western blot analysis. Using chronic intracerebroventricular administration of caspase inhibitors, z-VAD –fmk and z-DEVD-fmk, we inhibited apoptosis. Exploring consequences of apoptosis inhibition, activity of NF-kB was evaluated via western blotting. After β–amyloid peptide injection we observed an increase in TNF-α and caspase3 as an inflammatory cytokine and apoptotic marker, respectively (P<0.001 and P<0.0001, respectively). As a consequences of apoptosis inhibition, nuclear NF-κB was decreased and cytosolic NF-κB was increased and these changes were significant compared to Aβ-injected group (P<0.001 and P<0.05, respectively). Caspase inhibition as an initiator of apoptosis, probably by attenuation of NF-kB activity, protect cells from abnormal survival and proliferation.