TonEBP increases TRIM37

Aging-related microglial activation is associated with dendritic regression and spine loss in the aged brain. However, the microglia-mediated reductions of spine densities by Tonicity-responsive enhancer-binding protein (TonEBP) in the aged brain is yet unknown. We began to address this question by examining the effect of age on microglial activation and the TonEBP expression in mice. by using molecular and morphologic approaches, the roles of TonEBP in microglial activation and dendritic spines were examined in 12-month-old mice and Alzheimer's diseases (AD) mouse models. Here, we found the increased TonEBP in the hippocampus of aged mice and frontal cortex of AD patients. TonEBP haploinsufficiency reduced microglial activation and dendritic spine regression in 12-month aged mice compared to wild-type (WT) mice. We performed electron microscopy to supply interactions with microglial and synapses. We analyzed microglial processes and extracellular space in areas contacting spines and axon terminal, synaptic cleft, among the hippocampus CA1 of 12-month-old TonEBP haploinsufficient mice versus wild-type littermates. Furthermore, in amyloid-? oligomer (A?O)-injected AD mouse model, TonEBP haploinsufficiency inhibited the dendritic spine loss and improved memory deficits in AßO-treated mice compared to WT mice. These findings indicate that TonEBP may play an important role in aging-induced microglial activation and memory deficits. Overall design: TonEBP (+/-) mice and their Wild-type (WT) (TonEBP+/+) littermates were created by crossing TonEBP (+/-) mice. WT and TonEBP (+/-) mice were back-crossed on the C57BL/6J background for 5 to 6 generations to produce homogeneous animals, with no background effects on phenotypes.