HDAC7 Ubiquitination by the E3 Ligase CBX4 Is Involved in Contextual Fear Conditioning Memory Formation.

Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases.

Age and sex effects on the association between body composition and bone mineral density in healthy Chinese men and women.

OBJECTIVE: Many studies have examined the relationships between body composition and bone mineral density (BMD), but little attention has been given to how these relationships vary by age and sex. The aim of this study was to investigate the distributions of lean mass (LM), fat mass (FM), and BMD and the correlation between body composition and BMD in Chinese men and women of different ages. METHODS: In total, the body compositions of 1,475 men and 1,534 women aged 20 to 96 years were analyzed. Using dual-energy x-ray absorptiometry, we measured the BMD of the spine, femur, and total body and the LM, FM, and percentage of body fat (Fat %). The population was divided into groups based on age and sex: young, premenopausal, and postmenopausal women and young, middle-aged, and older men. The correlations between BMD and variables of body composition were investigated using the Pearson correlation test and multiple regression analysis. RESULTS: The peak BMD values of the spine, femur, and total body are observed in women aged 30 to 39, 20 to 29, and 30 to 39 years, respectively, and in men aged 20 to 29 years at all sites. The peak LM, FM, and Fat % values were observed at age 40 to 49, 60 to 69, and 70 to 79 years in women, respectively, and at 40 to 49, 70 to 79, and 70 to 79 years in men, respectively. A statistically significant correlation was observed between LM and BMD of all sites (r = 0.253-0.591, P < 0.01) in all groups. However, FM was significantly correlated to BMD only in postmenopausal women and older men (r = 0.089-0.336, P < 0.01). Fat % negatively correlated to BMD in young people (r = -0.169 to -0.366, P < 0.05). When stepwise regression models were analyzed, LM remained the strongest predictor of total body, spine, and femur BMD (standardized coefficients = 0.264-0.637, P < 0.001) in Chinese men and women of different ages. CONCLUSIONS: We believe that LM is the strongest predictor of BMD at all ages for Chinese men and women, even though positive correlations between FM and BMD existed in old people.