Maternal care and perinatal inflammation contributions to postnatal programming of anxiety and depression-related behavior

DEPINO AM; LUCCHINA L; PITOSSI F

Chicago, Estados Unidos de América

Congreso; Society for Neuroscience 2009; 2009

Society for Neuroscience

The perinatal development of the nervous system is influenced by different external and internal stimuli. Previous data show that maternal care and perinatal inflammation can induce long-term changes in anxiety and depression-related behavior. Our hypothesis is that both events act through interacting biological pathways during specific temporal windows to program adult behavior. Our aim is to study how these stimuli program adult behavior and whether there is an interaction between maternal care and inflammatory stimuli programming. To this aim, we used two protocols of maternal care variation in mice [Handling/Maternal Separation, and F1 offspring -C57BL/6J (C57) x Balb/c (Balb)] and injected the bacterial endotoxin lipopolysaccharide (LPS) at either of two previously reported sensitive development ages [gestational day 9 (GD9) or postnatal day 3 (PD3)]. The analysis of maternal behavior revealed that pups subjected to Maternal Separation (both Balb and C57 strains) and the F1 pups of C57 dams received more maternal attention. The analysis of the adult offspring revealed that handled C57 males spent more time in the open arms of elevated-plus maze (EPM) and in the illuminated side of the Light/Dark box. Maternally separated mice showed reduced immobility in both the tail suspension and the Porsolt tests. Control Balb adult mice showed increased locomotion in the EPM and reduced immobility in the Porsolt test, compared to both manipulated groups. The analysis of the F1 revealed that mice of the C57 pedigree showed increased anxiety-related behavior in the open field (OF) and EPM, and increased depression-related behavior in the Porsolt test. Postnatal (PD3) inflammatory stimulation had no long-term effects on C57 or Balb mice. LPS at PD3 reduced exploration in the OF in F1 females, regardless of pedigree. Conversely, prenatal LPS (GD9) led to increased anxiety and depression-related behavior in C57 male mice. We failed to observe a strong interaction between maternal care and inflammatory stimuli in the programming of adult anxiety and depression-related behavior in any of the experimental groups. In summary, we characterized a mouse model of postnatal programming of anxiety and depression-related behavior in which we can study the molecular mechanisms involved. Our behavioral results suggest that maternal care and inflammatory stimuli affect perinatal programming of adult behavior presumably through different molecular and cellular mechanisms.