Overexpression of serum amyloid a 1 induces depressive-like behavior in mice.

Abstract

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.

• Authors: Woo Young Jang, Bo-Ram Lee, Jain Jeong, Younghun Sung, Minjee Choi, Park Song, Hyerim Kim, Soyoung Jang, Hyunmin Kim, Kyung-Il Joo, Jeong-Woong Lee, Yeon Sik Choo, Eunjoo Kim, Zae Young Ryoo
• Journal: Brain research (Brain Res) Vol. 1654 Issue Pt A Pg. 55-65 (Jan 01 2017) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 27608955 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• RNA, Messenger
• Saa2 protein, mouse
• Serum Amyloid A Protein

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Blood-Brain Barrier (metabolism, pathology)
• Brain (metabolism, pathology)
• Capillary Permeability (physiology)
• Depressive Disorder (metabolism, pathology)
• Disease Models, Animal
• Liver (metabolism)
• Mice, Transgenic
• Microglia (metabolism, pathology)
• RNA, Messenger (metabolism)
• Recognition, Psychology (physiology)
• Serum Amyloid A Protein (genetics, metabolism)
• Social Behavior