Increased Inflammatory Response Both in Brain and in Periphery in Presenilin 1 and Presenilin 2 Conditional Double Knock-Out Mice

Abstract

It has been reported that conditional double knockout of presenilin-1 and presenilin-2 in forebrain of mice (dKO mice) induce symptoms most analogous to that of neurodegenerative diseases, especially Alzheimer's disease, however, there is no deposition of extra amyloid-β (Aβ₄₀ or Aβ₄₂) in dKO brain. In the present study, we thoroughly measured the inflammatory response in dKO mice, which is another global symptom in neurodegenerative diseases. We demonstrated that glial cells were dramatically activated from early age (3 months) in dKO brain when compared with control mice. In addition, complement C1qα and C4, the key components in the classical complement pathway, were also stimulated in dKO mice brain. Antibody array and ELISA analysis indicated that cytokine and chemokine levels were also significantly increased in dKO brain. Moreover, we found that leukocytes were elevated beginning at 6 months of age, and multiple inflammatory mediators changed in dKO mice serum at 9 months, showing that the inflammatory responses gradually expanded to systemic tissue. These findings confirm that presenilins double knockout results in robust inflammatory response both in brain and in periphery and suggest that dKO mice may be useful to further understand the effects of inflammation on the pathological processes of neurodegenerative diseases.