Reversal of Social Recognition Deficit in Adult Mice with MECP2 Duplication via Normalization of MeCP2 in the Medial Prefrontal Cortex

Methyl-CpG binding protein 2(MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing.Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome,a severe neurodevelopmental disorder characterized by intellectual disability,motor dysfunction,heightened anxiety,epilepsy,autistic phenotypes,and early death.Reversal of the abnormal phenotypes in adult mice with MECP2 duplication(MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated.However,whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown.Here,we found that MECP2-TG mice showed a significant social recognition deficit,and were prone to display aversive-like behaviors,including heightened anxiety-like behaviors and a fear generalization phenotype.In addition,reduced locomotor activity was observed in MECP2-TG mice.However,appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice.Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors.We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex(mPFC) and bed nuclei of the stria terminalis(BST) of adult MECP2-TG mice,and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit.These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice,and provide new insight into potential therapies for MECP2 duplication syndrome.

Age Identity and Elderly Job Participation in China

In the context of rising life expectancy,there is a significant discrepancy between Chinese seniors’self-perceptions of the start of old age and the expectations of society around this age.The traditional paradigm,which forecasts individual economic behavior and formulates economic policies based on societal standards of age,is put to the test by this disparity.This study,which draws from the China Longitudinal Aging Society Survey(CLASS),examines the factors,processes,and improvement strategies that affect how older people choose to work.The following are our conclusions:(i)Chinese elderly believe their old age starts from 70 years on average;delaying perceived old age is a denial of aging and raises the likelihood of finding work.Elders who are youthful at heart have a 2.4%higher chance of remaining employed than elders who are old at heart.(ii)In contrast to old-at-heart elders,young-at-heart elders are more likely to maintain their middle-age lifestyles,continue working,become motivated to engage in social activities,and gain the confidence to face challenges and continue in their career.(iii)If the perceived old age is above 70 years,the milestone event of aging is retirement from work,and there are external pressures,particularly pressures from family intergenerational support,the perception of old age will have a more proactive impact on older workers.(iv)Despite rising pension benefits,older people’s decision to remain in the workforce is still heavily influenced by their perception of their age.However,this effect is notably gender-specific,as older women’s decision to remain in the workforce is not greatly influenced by their own perception of their age.