TonEBP Haploinsufficiency Attenuates Microglial Activation and Memory Deficits in Middle-Aged and Amyloid β Oligomer-Treated Mice
Jong Youl Lee,
Eun Ae Jeong,
Jaewoong Lee,
Hyun Joo Shin,
So Jeong Lee,
Hyeong Seok An,
Kyung Eun Kim,
Won-Ho Kim,
Yong Chul Bae,
Heeyoung Kang,
Gu Seob Roh
Affiliations
Jong Youl Lee
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Eun Ae Jeong
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Jaewoong Lee
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Hyun Joo Shin
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
So Jeong Lee
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Hyeong Seok An
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Kyung Eun Kim
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Won-Ho Kim
Division of Cardiovascular Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju 28159, Republic of Korea
Yong Chul Bae
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 41944, Republic of Korea
Heeyoung Kang
Department of Neurology, College of Medicine, Gyeongsang National University Hospital, Gyeongsang National University, Jinju 52727, Republic of Korea
Gu Seob Roh
Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
Age-related microglial activation is associated with cognitive impairment. Tonicity-responsive enhancer-binding protein (TonEBP) is a critical mediator of microglial activation in response to neuroinflammation. However, the precise role of TonEBP in the middle-aged brain is not yet known. We used TonEBP haploinsufficient mice to investigate the role of TonEBP in middle-aged or amyloid β oligomer (AβO)–injected brains and examined the effect of TonEBP knockdown on AβO-treated BV2 microglial cells. Consistent with an increase in microglial activation with aging, hippocampal TonEBP expression levels were increased in middle-aged (12-month-old) and old (24-month-old) mice compared with young (6-month-old) mice. Middle-aged TonEBP haploinsufficient mice showed reduced microglial activation and fewer memory deficits than wild-type mice. Electron microscopy revealed that synaptic pruning by microglial processes was reduced by TonEBP haploinsufficiency. TonEBP haploinsufficiency also reduced dendritic spine loss and improved memory deficits in AβO-treated mice. Furthermore, TonEBP knockdown attenuated migration and phagocytosis in AβO-treated BV2 cells. These findings suggest that TonEBP plays important roles in age-related microglial activation and memory deficits.
