The integrity of perineuronal nets in the amygdala as a key factor in the resilience to social isolation stress in old mice

Major depression is the most prevalent neuropsychiatric disorder in elderly population, affecting more than 20% individuals over 60 years old, especially women. In this age range, social isolation is a major risk factor for depression. While there is a significant positive association between social isolation and depression in the elderly population, the neurobiological basis of this association is complex and still poorly understood. Evidence from animal models and human studies indicates that neuroplasticity, especially that of limbic brain regions, is impaired in depression but, till date, scarce studies address this question in older population. In this regard, animal models devoid of human cultural connotations represent a crucial tool. In the present study, we investigated the impact of chronic isolation stress (CIS) and a subsequent resocialization period in aged male and female mice ([~] 21 months-old), focusing our attention on affective symptoms and the plasticity of parvalbumin-expressing (PV+) neurons in the lateral/basolateral amygdala (LA/BLA). We found that CIS impaired affective behaviour and LA/BLA plasticity only in females. Specifically, CIS induced depressive-like symptoms and decreased the integrity of perineuronal nets (PNN). Resocialization effectively rescued all these impairments. Old males were not affected by CIS but in social conditions showed higher PNN integrity (less plasticity) than females. All together, our results demonstrate that old females are less resilient to CIS than old males and point to the integrity of PNN in the LA/BLA as a key regulator of depressive-like symptoms induced by social isolation.