title: 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-beta (Abeta(40) or Abeta(42)) 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 C1qalpha 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.
authors: Shanghai Institute of Brain Functional Genomics, and Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal University, Shanghai 200062, China.
authors: Xu
authors: X
authors: Jiang
authors: Dongli
authors: D
authors: Zhang
authors: Jianting
authors: J
authors: Shi
authors: Yiqun
authors: Y
authors: Chen
authors: Ping
authors: P
authors: Zhang
authors: Bing
authors: B
authors: Mei
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C538897:amyloid beta-protein (40-42); C528900:glial fibrillary astrocytic protein, mouse