Stress exposure early in life is implicated in various behavioural and somatic diseases. experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival.Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxincontaining bacterial lawn. in contrast, adult worms do not exhibit aversive behaviour towards stressassociated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress.Associative learning ensures rapid, efficient adaptation to already experienced, re-emerging conditions 1,2 . Re-encountering sensory cues associated with a relevant past experience retrieves the memory and elicits a complex response corresponding to the past incident. Associative memories are generally transient. In contrast, a peculiar learning process takes place early in life during a specific time window, called the critical or sensitive period and gives rise to especially persistent memories. Hence the name, imprinting, which was coined by Konrad Lorenz who observed that newly hatched birds created a strong bond with the first moving object seen 3 . Besides visual cues, olfactory memories driving adult behaviours have been recognized in several vertebrate species, including the homing of salmons to reproduce in the creek they were born 4 and preference for odours associated perinatally with food in mammals 5,6 . Hence, imprinting serves as the biological basis of secure, long lasting attachment to qualities essential for individual and/or species' survival. In further support of the profound, life-long impact of imprinted memories, a growing body of evidence shows that facing adversity in the critical period is connected to different cognitive and affective disorders and are accompanied by brain epigenetic, structural and endocrine alterations 7-9 . On the other hand, early life stress predispose to increased telomere erosion, metabolic and cardiovascular diseases in adulthood ultimately affecting healthy lifespan 10-12 . Some of the open questions emerging from th...
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