title: Enhanced brain performance in mice following postnatal stress.
abstract: 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.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanita', via Regina Elena 299, 00161 Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Loizzo
authors.forename: Santi M
authors.initials: SM
authors.lastname: Spampinato
authors.forename: Gabriele
authors.initials: G
authors.lastname: Campana
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: Andrea
authors.initials: A
authors.lastname: Fortuna
authors.forename: Loredana
authors.initials: L
authors.lastname: Costa
authors.forename: Anna
authors.initials: A
authors.lastname: Capasso
authors.forename: Palmiero
authors.initials: P
authors.lastname: Monteleone
authors.forename: Paolo
authors.initials: P
authors.lastname: Renzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Loizzo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone