TonEBP Haploinsufficiency Attenuates Microglial Activation and Memory Deficits in Middle-Aged and Amyloid β Oligomer-Treated Miceopen access
- Authors
- Lee, Jong Youl; Jeong, Eun Ae; Lee, Jaewoong; Shin, Hyun Joo; Lee, So Jeong; An, Hyeong Seok; Kim, Kyung Eun; Kim, Won-Ho; Bae, Yong Chul; Kang, Heeyoung; Roh, Gu Seob
- Issue Date
- Nov-2023
- Publisher
- MDPI
- Keywords
- TonEBP; microglia; hippocampus; aging; amyloid beta
- Citation
- CELLS, v.12, no.22
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELLS
- Volume
- 12
- Number
- 22
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/68612
- DOI
- 10.3390/cells12222612
- ISSN
- 2073-4409
2073-4409
- Abstract
- 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 beta oligomer (A beta O)-injected brains and examined the effect of TonEBP knockdown on A beta O-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 A beta O-treated mice. Furthermore, TonEBP knockdown attenuated migration and phagocytosis in A beta O-treated BV2 cells. These findings suggest that TonEBP plays important roles in age-related microglial activation and memory deficits.
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