Enhanced brain performance in mice following postnatal stress.

The double postnatal stress model (brief maternal separation plus sham injection daily applied from birth to weaning) induces metabolic alterations similar to type 2 diabetes in young-adult male mice. We verify whether 1) the stress also induces brain metabolic-functional alterations connected to diabetes and 2) different alterations are modulated selectively by two stress-damaged endogenous systems (opioid- and/or ACTH-corticosteroid-linked). Here, diabetes-like metabolic plus neurophysiologic-neurometabolic parameters are studied in adult mice following postnatal stress and drug treatment. Surprisingly, together with 'classic' diabetes-like alterations, the stress model induces in young-adult mice significantly enhanced brain neurometabolic-neurophysiologic performances, consisting of decreased latency to flash-visual evoked potentials (- ~8%); increased level (+ ~40%) and reduced latency (- ~30%) of NAD(P)H autofluorescence postsynaptic signals following electric stimuli; enhanced passive avoidance learning (+ ~135% latency); and enhanced brain-derived neurotrophic factor level (+ ~70%). Postnatal treatment with the opioid receptor antagonist naloxone prevents some alterations, moreover the treatment with antisense (AS; AS vs proopiomelanocortin mRNA) draws all parameters to control levels, thus showing that some alterations are bound to endogenous opioid-system hyper-functioning, while others depend on ACTH-corticosterone system hyper-functioning. Our stress model induces diabetes-like metabolic alterations coupled to enhanced brain neurometabolic-neurophysiologic performances. Taken all together, these findings are compatible with an 'enduring acute-stress' reaction, which puts mice in favorable survival situations vs controls. However, prolonged hormonal-metabolic imbalances are expected to also produce diabetes-like complications at later ages in stressed mice.