Editorial: Brain health across the lifespan: nutritional interventions and physical exercise for healthy aging.

The extent and type of care that offspring receive in early life can affect mental and physical health across the lifespan. In humans, adverse childhood experiences are associated with increased risk for mental health syndromes including depression, anxiety, and addiction, and physical health challenges including cardiovascular disease, metabolic disease, and even immune disorders and cancer (; ; ). Rodent models of early-life stress (ELS) have been a useful tool for understanding the consequences of the early environment on offspring wellbeing and neurodevelopment. Maternal separation is a widely used ELS paradigm which involves separating pups from their dams for several hours per day (; ; ; ). This separation is thought to model aspects of deprivation (). Maternal separation paradigms vary across research groups as to timing or age of separation, whether pups or dams are separated from the home cage, and whether siblings are kept together during separation or housed individually (; ). Maternal separation has been found to increase corticosterone response to stressors, altering hypothalamic-pituitary-adrenal (HPA)-axis regulation, emotional dysregulation, and anxiety-and-depression-like behaviors (; ; ; ; ; ; ). Interestingly, when separated pups are reunited with their mothers after both short or long periods of separation, dams have been observed to increase their care towards pups (; ; ; ; ; ; ; ; ). Dams, or indeed other caring alloparents, will naturally retrieve scattered pups to a nest (; ; ) and begin licking and grooming pups (; ), which is associated with positive stress regulation and other positive developmental effects (; ; ). Together, these observations have begged the question of whether maternal separation paradigms prompt an increase in care that compensates for the stress of separation (). While many long-term negative consequences of maternal separation have been documented, these observations nevertheless call into question the effects of the paradigm. A few studies have made multiple observations across the day to determine how long increases in post-reunion care persist (; ; ), though none have explicitly calculated effects relative to loss of care during separation. It is therefore not currently known whether these increases in care may actually make up for the care missed during the period of separation. To help reconcile the literature, we sought to determine whether maternal separation increases maternal care transiently or throughout the day in C57BL/6 mice. We hypothesized that increased care following dam-pup reunion may be transient and insufficient to compensate for the lack of care experienced during the hours of separation. To test this, we observed home cage behaviors at three time points throughout the day from postnatal days P2-17. We used an ELS paradigm in which pups are separated from their dams for three-four hours per day during a late juvenile period from postnatal days P10-17, allowing us to observe how ELS alters maternal behavior both within and across groups (). By including multiple periods of observation before the start of maternal separation, immediately following pup reunion, and several hours after reunion, we sought to provide a more nuanced profile of how maternal separation disrupts total contact and dynamic timing of maternal care.