Enrich The Physical Environment To Correct Neuropsychological Behavior Damage Caused By Early Social Isolation

A selective reversal of enriched physical environment on neuropsychiatric impairments induced by early social isolationEarly social isolation(SI)produces a variety of emotional,behavioral and cognitive abnormalities.Conversely,environmental enrichment(EE),a complicated social and physical construct,offers beneficial effects on brain plasticity and development.However,whether or not exclusive physical EE is sufficient to reverse the adverse consequences of adolescent SI remains unclear.Here we reported that 1 month-old solitary mice housed in the EE for 8 weeks fully corrected spatial cognitive dysfunction,but did not ameliorate social interaction deficits and increased anxiety-like behavior.Pathological analyses revealed that the enriched environment decreased neuronal apoptosis,synaptic protein loss,myelination defect and microglial activation in the hippocampus,but not medial prefrontal cortex(mPFC)of mice housed singly.Moreover,increased nuclear factor-kappa B and interleukin-1? levels,and downregulation of brain-derived neurotrophic factor signaling pathway were normalized in the hippocampus rather than mPFC of these animals.Our results revealed a brain region-specific effectiveness of physical EE in remediating brain impairment of adolescent SI mice,with a complete reversal of hippocampus-dependent cognitive dysfunctions,but without mitigation of mPFC associated anxiety and social interaction defects.This finding emphasizes the irreplaceable role of social life for the early brain development.Enriched physical environment counteracts damaged effects of early social isolation on congitive function of APP/PS1 miceAlzheimer's disease(AD)is a most neurodegenerative disorder characterized by progressive memory deficits and cognitive decline.Social isolation(SI),including living alone,a diminished social network,and less participating in activities with others,has been associated with an increased risk of AD.Consistently,SI accelerates cognitive deficits in many AD models.In contrast,environmental enrichment(EE),refering to engagement in higher levels of mental and physical activity via education,occupation and recreation,may lower risk of developing AD and improve cognitive performance in various AD models via an amyloid-related or unrelated mechanism.However,whether EE intervention can protect against detrimental effects of SI on the pathology of AD remains unclear.Here,we investigated effects of 8-week environmental stimulation in APPswe/PSEN1dE9(APP/PS1)mice,a family AD transgenic model,which received SI from 1 month of age.The results showed that EE rescued SI-induced cognitive deficits associated with decreased levels of inflammatory reactivation,reduced cell apoptosis,improved synaptic plasticity and enhanced neurogenesis,rather than an alteration in A? neuropathology.However,EE had no ameliorating effects on impairments of social interaction,exploring activity and anxiety-like behaviors of APP/PS1 mice.These results strongly implicate the selective reversal of enriched physical environment on cognitive and emotional impairments induced by social isolation in the early stage of AD.