Early enriched physical environment reverses impairments of the hippocampus, but not medial prefrontal cortex, of socially-isolated mice

- The enriched environment reverses cognitive impairment caused by social isolation.
- The enriched environment reverses hippocampal structural impairment.
- The enriched environment doesn't mitigate social interaction deficits and anxiety.
- The enriched environment doesn't rescue impairment of medial prefrontal cortex.

Early 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 early SI remains unclear. Here we reported that 1 month-old solitary mice housed in the EE for 8 weeks corrected spatial cognitive dysfunction, but did not ameliorate social interaction deficits and increased anxiety-like behavior. Pathological analyses revealed that the enriched environment decreased cellular 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-kappaB and interleukin-1β 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.