Ailen Alba Colapietro

Early-life adversity during critical developmental windows markedly increases vulnerability to neuropsychiatric disorders later in life. Although adult behavioral and neurobiological alterations following early stress are well documented, the early emerging phenotypes and their underlying cellular and molecular mechanisms during juvenile development remain poorly understood. In this study, we utilized the translational Scarcity-Adversity Model (SAM) to investigate early behavioral alterations and hippocampal neuroplasticity in juvenile offspring. We characterized the behavioral profile of juvenile subjects exposed to SAM to identify early manifestations of vulnerability. Next, we evaluated hippocampal neurogenesis by quantifying neural progenitor cell proliferation immediately following stress exposure (at postnatal day 13, PND 13) and the short-term survival of newborn neurons (1 week post-labeling) in the dentate gyrus of juvenile offspring. Furthermore, given the functional compartmentalization of the hippocampus, we measured the protein expression of mature BDNF (mBDNF) and its precursor proBDNF across both dorsal and ventral domains. At the behavioral level, SAM-exposed juvenile offspring exhibited increased immobility in the forced swim test alongside impaired spatial memory in the novel object location task. Regarding hippocampal neurogenesis, SAM exposure did not alter immediate progenitor proliferation at PND 13; however, it produced a significant, male-specific reduction in newborn neuron survival, concomitant with a trend toward decreased mBDNF levels in males. Together, these results provide critical insight into the early neurodevelopmental trajectories triggered by early-life adversity, identifying early behavioral impairments and male-specific neuroplastic deficits as key juvenile markers of vulnerability preceding adult psychopathology.

Early parental care is critical for the development of cortico-limbic circuits regulating stress responses and emotional well-being. Conversely, infant maltreatment can increase susceptibility to mood disorders—such as anxiety and depression—and impair stress-coping abilities. Here, we employed the Scarcity-Adversity Model (SAM) in rats, limiting nesting resources from postnatal days 8–12, to examine its effects on maternal and adult offspring behavior. SAM-exposed mothers exhibited fragmented care and increased violence towards pups. By postpartum day (PPD) 13, maternal fecal corticosterone metabolites (FCM) were elevated, indicating heightened stress. At weaning, SAM dams also showed increased anxiety-like behavior in the Elevated Plus Maze (EPM), suggesting significant emotional alterations. In adulthood, SAM-exposed offspring underwent anxiogenic tests. Both male and female SAM offspring showed increased latency to enter open arms and reduced risk-assessment in the EPM, though females displayed anxiolytic-like behavior in the Light-Dark Box. Male SAM rats had reduced locomotion in the Open Field, earlier onset and increased immobility in the Forced Swim, and increased latency to groom in the Sucrose Splash. When exposed to acute stress, male SAM rats had lower FCM levels, consistent with their passive stress reactivity. These findings confirm SAM induces long-lasting, sex-specific changes in risk-taking, novelty responsiveness, and stress reactions, underscoring the importance of early nurturing in promoting well-being and reducing psychopathological risk.