The use of poly(I:C) as an innate immune response activator is advantageous because it avoids the use of infectious agents within the working environment, and treatments can towards be standardized, facilitating comparisons between experiments and between laboratories. However, it should be noted that i.v. or i.p. injection of poly(I:C) do not exactly reproduce a natural viral infection, as viruses most commonly infect epithelial cells of the respiratory and digestive tracts, and very rarely infect and replicate in the blood stream or in the peritoneum. Therefore, the immune cells activated by i.v. or i.p. administration of poly(I:C) are likely to be different than the ones activated during an ordinary viral infection. Activation of immune cells in different tissues may lead to the generation of an innate immune response with different profiles of cytokine production.

Thus, the profile IRSF in maternal serum observed in the present study after i.p. administration of poly(I:C) may not be exactly the same as the profile observed after an i.v. injection of poly(I:C) or after a common viral infection. Nevertheless, the profile of IRSF detected in fetal brain homogenates did not correlate with the profile observed in maternal serum, indicating that IRSF production was regulated within the fetus or in the placenta. This suggests that, regardless of the route of administration, the effect of poly(I:C) on IRSF expression levels in fetal brains is expected to be similar to the effect caused by a natural viral infection.

Maternal exposure to poly(I:C) close to the end of the mouse pregnancy (GD16 to GD17) impairs associative and reversal learning, exploration in open field and social behavior of the offspring. In addition, an increase in anxiety and a decrease in pre-pulse inhibition have been observed in post-pubertal animals exposed to poly(I:C) during pregnancy, indicating that innate immune activation by poly(I:C) during the final period of the pregnancy affects CNS development and causes long-lasting impairments of animal behaviors associated with psychiatric symptoms [28,40-42]. The developmental stage of the mouse CNS at GD16 correlates with GD68 to GD94 of human brain development, depending on whether cortical (GD93.3), limbic (GD68.4) or non-cortical/limbic events (GD73.7) are compared [34-36]. At this developmental stage, neurogenesis is
fatty acids and glucose can compete as oxidative fuels within muscle [for review, see Randle (37)]. Additionally, increased triglyceride (TG) content has been associated with insulin resistance in various insulin-sensitive tissues (21, 24, 29, 31, 41, 43), and accumulation of lipid species within Entinostat cells might directly affect cell insulin signaling (42).