Previous studies indicate that individuals exposed to stress in juvenility are more prone to suffer from stress-related psychopathologies in adulthood. Evidence suggests that exposure to enriched environment (EE) conditions alleviates juvenile stress (JVS) effects. Exposure to stress has been found to affect immune responses to challenges, but whether JVS has long-term effects on inflammatory processes remains unclear. Here, we examined the impact of JVS on inflammatory processes in adulthood, and the effects of exposure to EE conditions. Adult rats exposed to JVS showed elevated levels of blood monocytes after induction of peritoneal inflammation. This was associated with higher concentration of blood chemokine ligand type 2 (CCL2), but lower levels of its receptor, chemokine receptor type 2 (CCR2) on these monocytes, indicating reduced ability of these monocytes to be recruited to the inflammatory site. In accordance, JVS led to reduced levels of recruited macrophages at the peritoneal cavity, as well as a reduced activation ratio for the release of peritoneal interleukin-10 (IL-10) by lipopolysaccharide (LPS) activation. EE conditions, which fully reversed the anxiety-like behavior resulting from exposure to JVS, did not reverse JVS-induced alterations in blood concentration of monocytes or peritoneal macrophages, but affected IL-10 activation ratio. This effect was associated with a compensatory elevation of the peritoneal CCL2-CCR2 axis. Our results demonstrate long-term metaplasticity-like effects of JVS, which alter inflammatory processes in response to immune challenges in adulthood. Our results also raise the possibility that EE does not simply reverse the effects of JVS but rather indirectly modulates its impact.

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The formation of associative representations and their retrieval from episodic memory are vital cognitive functions. However, it is unclear to what extent retrieval of the basic component relations of episodic memory, identity, time, and space, requires different or shared brain mechanisms. In the current study, we employed EEG to track the time courses of electrophysiological correlates of retrieval processes of memory for identity relations, temporal order, and spatial configuration. Participants engaged in pair-associate learning of serially presented and spatially configured object picture pairs, followed by discrimination of identity, spatially, or temporally intact and rearranged pairs. Event-related brain potentials (ERPs) revealed distinct patterns of activity during successful retrieval of identity, spatial, and temporal relations that differed by the status of association, across the three retrieval time windows examined (300-500, 500-800, and 800-1000 ms). The identity relations condition was distinguished by a widespread greater negative-going deflection for rearranged relative to intact pairs in all three time windows. For the temporal relations condition, we observed a widespread more negative-going deflection for rearranged than intact pairs, significant in the second time window only. For the spatial relations condition, there was a widespread positive-going deflection greater for rearranged than for intact pairs, significant in the early and in middle time windows. These patterns of activity suggest that retrieval of associative memory traces for identity, spatial, and temporal relationships involve dynamically different processes, which may partially rely on different sets of basic associative mechanisms.

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