Early attachment disruption differentially enhances multiple signs of microglia activation in the prefrontal cortex, hippocampus, and preoptic area of periadolescent guinea pigs.

Early attachment disruption increases susceptibility to depression in adolescent and adult populations. These effects often appear to be mediated by sensitized inflammatory signaling. Guinea pigs afford a unique model to investigate sensitization of inflammatory-mediated depression following early-life attachment disruption. This study examined the hypothesis that early attachment disruption primes microglia so that they show greater stress-induced activation in later life. We used immunohistochemistry and confocal microscopy to examine multiple measures of microglia activation in critical brain regions of periadolescent guinea pigs that had either not previously been disturbed, received a single 3-h isolation 24 h earlier, or received multiple 3-h isolations in the late preweaning period, followed by a final 3-h isolation 24 h prior to brain collection. In light of large sex differences in microglia activity reported in other rodents, only males were included in this initial assessment. Early-isolated guinea pigs exhibited depressive-like behavior that sensitized with repeated isolation. Moreover, when isolated later in periadolescence early-isolated animals displayed multiple, clear, and consistent signs of microglia activation in the prefrontal cortex and hippocampus, sites chosen for their relevance to human depression. This evidence of priming was particularly clear in the hippocampus where the final isolation increased all six measures of microglia but only in early-isolated guinea pigs. In the preoptic area, the final isolation consistently increased activation regardless of early isolation history. These initial results, while limited to males, provide support for the notion that the priming of microglia by early attachment disruption may promote the development of depression in later life.