Overexpression of serum amyloid a 1 induces depressive-like behavior in mice.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities. In AD, amyloid β (Aβ) protein aggregates in the brain of patients, forming amyloid plaques. Aβ plaques are known to be surrounded by activated microglial cells. Serum amyloid A (SAA) is elevated from several hundred to 1000-fold as part of the immune response against various injuries, including trauma, infection, and inflammation. Additionally, continuous elevation of SAA is related to the development of amyloidosis. This study was designed to identify the relationship between SAA1 and AD using liver specific SAA1 overexpressing mice (TG), because SAA1 is expressed in the liver during the acute phase. We detected exogenous SAA1 expression in the brain of TG mice. This result implies that liver-derived SAA1 migrates to the brain tissues. Thus, we confirmed that the blood brain barrier (BBB) functioned normally using Evans-blue staining and CARS. Furthermore, our results show an increase in the accumulation of the 87kDa form of Aβ in TG mice compared to wild type mice (WT). Additionally, the number of microglial cells and levels of pro-inflammatory cytokines were increased. Next, we investigated the relationship between SAA1 and depression by performing social interaction tests. The results showed that TG mice have a tendency to avoid stranger mice and an impaired social recognition. In conclusion, the SAA1 TG mouse model is a valuable model to study depression.
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Woo Young
WY
Jang
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea; Division of Nano & Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Republic of Korea.
Bo-Ram
BR
Lee
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Jain
J
Jeong
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Younghun
Y
Sung
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Minjee
M
Choi
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Park
P
Song
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Hyerim
H
Kim
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Soyoung
S
Jang
Division of Nano & Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Republic of Korea.
Hyunmin
H
Kim
Division of Nano & Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Republic of Korea.
Kyung-Il
KI
Joo
Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
Jeong-Woong
JW
Lee
Department of Biology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
Yeon Sik
YS
Choo
Division of Nano & Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Republic of Korea. Electronic address: ejkim@dgist.ac.kr.
Eunjoo
E
Kim
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea. Electronic address: jaewoong64@hanmail.net.
Zae Young
ZY
Ryoo
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability / Q000502:physiology; D003866:Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior
D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein
Amyloid β; Behavior test; Depression; Inflammation; Serum amyloid A; Transgenic mice