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Early-life stress modulates the development of cortico-limbic circuits and increases vulnerability to adult psychopathology. Given the important stress-buffering role of endocannabinoid (eCB) signaling, we performed a comprehensive investigation of the developmental trajectory of the eCB system and the impact of exposure to early life stress induced by repeated maternal separation (MS; 3 h/day) from postnatal day 2 (PND2) to PND12. Tissue levels of the eCB molecules anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured after MS exposures, as well under basal conditions at juvenile (PND14), adolescent (PND40) and adult (PND70) timepoints in the prefrontal cortex (PFC), amygdala and hippocampus. We also examined the effects of MS on CB1 receptor binding in these three brain regions at PND40 and PND70. AEA content was found to increase from PND2 into adulthood in a linear manner across all brain regions, while 2-AG was found to exhibit a transient spike during the juvenile period (PND12-14) within the amygdala and PFC, but increased in a linear manner across development in the hippocampus. Exposure to MS resulted in bidirectional changes in AEA and 2-AG tissue levels within the amygdala and hippocampus and produced a sustained reduction in eCB function in the hippocampus at adulthood. CB1 receptor densities across all brain regions were generally found to be downregulated later in life following exposure to MS. Collectively, these data demonstrate that early life stress can alter the normative ontogeny of the eCB system, resulting in a sustained deficit in eCB function, particularly within the hippocampus, in adulthood.

Background COVID-19 is an emerging pathogen that has caused a global pandemic, with New York City as one of its epicenters. Data are still forthcoming if pregnant women are more vulnerable to COVID-19, as they are with influenza. Additionally, it is not known if infants born to COVID-19 positive women are at risk of being infected at birth. Methods In March 2020, our hospital instituted a policy of testing all pregnant women presenting for active labor and scheduled C-section or induction of labor, with a nasopharyngeal swab that was sent for RT-PCR qualitative SARS-CoV-2 assay (Roche Cobas® 6800). Upon birth, infants were also tested, unless the parent did not give consent. We retrospectively reviewed the COVID-19 test results of all pregnant women and their infants, from March 23 through May 31, 2020 using our infection control surveillance system (VigiLanz®). We also reviewed the electronic medical record (EPIC®) for documentation of any symptoms consistent with COVID-19 infection either prior to hospitalization or during the hospital stay. Results A total of 415 women and 72 infants were tested for SARS-CoV-2. Of the 415 women tested, 41 (9.9%) were positive. Of the 72 infants tested, 2 (2.8%) were positive and concordant with their birth parent. Only 1 (2.4%) of the women who tested positive was symptomatic. The remaining 40 (97.6%) women did not report any symptoms of COVID-19 during labor. Neither of the two positive infants displayed any signs or symptoms of COVID-19. Of the 41 women who were positive, 5 did not consent to have their infant tested. The one symptomatic woman who tested positive for COVID-19 had an infant who tested negative by PCR. Conclusion During the first wave of the COVID-19 pandemic, we found 9.9% (41/415) of pregnant women presenting for labor tested positive for SARS-CoV-2. Among the 41 women who tested positive, only 1 (2.4%) had symptoms on presentation and only 2 newborn infants tested positive. Our data suggests that pregnant women may not be at increased risk for complications from COVID-19 disease and are not likely to transmit the disease to their infants during labor. Disclosures All Authors: No reported disclosures

Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes coincident with adolescence. An emerging line of research has indicated that stressors experienced during this crucial developmental stage may affect the trajectory of this neural maturation and contribute to the increase in psychological morbidities, such as anxiety and depression, often observed during adolescence. In this review, we discuss the short- and long-term effects of periadolescent stress exposure on the structure and function of the brain. More specifically, we examine how stress at prepubertal and early adolescent stages of development affects the morphological plasticity of limbic and cortical brain regions, as well as the enduring effects of adolescent stress exposure on these brain regions in adulthood. We suggest that, due to a number of converging factors during this period of maturation, the adolescent brain may be particularly sensitive to stress-induced neurobehavioral dysfunctions with important consequences on an individual’s immediate and long-term health and well-being.

The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult, as well as developing brain, possess a remarkable ability to show reversible structural and functional plasticity in response to stressful and other experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. This is particularly evident in the hippocampus, where all three types of structural plasticity have been recognized and investigated, using a combination of morphological, molecular, pharmacological, electrophysiological and behavioral approaches. The amygdala and the prefrontal cortex, brain regions involved in anxiety and fear, mood, cognitive function and behavioral control, also show structural plasticity. Acute and chronic stress cause an imbalance of neural circuitry subserving cognition, decision making, anxiety and mood that can increase or decrease expression of those behaviors and behavioral states. In the short term, such as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive; but, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic or mood anxiety disorders. We shall review cellular and molecular mechanisms, as well as recent work on individual differences in anxiety-like behavior and also developmental influences that bias how the brain responds to stressors. Finally, we suggest that such an approach needs to be extended to other brain areas that are also involved in anxiety and mood. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Nearly 12% of US children are exposed to intense adverse experiences. Research has demonstrated that these experiences can negatively impact adult health, often resulting in psychopathology. Less attention, however, is given to the impact of childhood adverse experiences on childhood health and wellbeing. Using a rodent model of chronic juvenile stress (restraint 6 h daily from postnatal day 20 to 41), we report that chronic stress has significant immediate morbidities in both males and females during this developmental window. Specifically, we demonstrate that chronic juvenile stress produces depressive-like behavior and significant neuronal remodeling of brain regions likely involved in these behavioral alterations: the hippocampus, prefrontal cortex and amygdala. Chronically stressed males and females exhibit anhedonia, increased locomotion when exposed to novelty, and altered coping strategies when exposed to acute stress. Coincident with these behavioral changes, we report simplification of dendrites in the hippocampus and prefrontal cortex and concurrent hypertrophy of dendrites in the amygdala. Taken together, these results demonstrate that chronically stressed juveniles exhibit aberrant behavioral responses to acute challenges that occur in conjunction with stress-induced remodeling of brain regions intimately involved in regulating emotionality and stress reactivity. Further, the absence of sex differences in our reported stress responses, likely speaks to the decreased sensitivity of immature HPA regulating brain regions to sex hormones.

Early life stress produces long-term alterations in cognition, emotionality, and stress responsiveness. The stress-sensitive hippocampal formation plays a role in producing many of these alterations. We report that adult male rats exposed to early life stress, in the form of maternal separation (MS), exhibit baseline impairment of hippocampal dependent memory and following three weeks of chronic restraint stress (CRS) exhibit heightened anxiety-like behavior and alterations in the morphology of hippocampal CA3 pyramidal neurons. Specifically, as measured by the object placement task, MS offspring demonstrated impaired spatial memory compared with nonmaternally separated rats (NMS). Moreover, compared with NMS rats, subsequent CRS exposure of MS rats increased novelty-induced corticosterone secretion and potentiated anxiety-like behavior as measured by the elevated plus maze. Further, CRS exposed MS rats did not exhibit shortening of apical dendritic length compared with nonstressed MS rats, whereas CRS exposed NMS rats did show significant dendritic shrinkage compared with nonstressed NMS rats. The blunted CRS-induced remodeling of apical dendritic length in MS rats is likely due to a baseline deficiency in dendritic length; MS rats exhibit a trend towards shorter apical dendrites in comparison to NMS rats. CRS exposure in both MS and NMS rats, however, induced a reduction in apical dendritic branching. Finally, there was a significant correlation between apical dendritic length and novelty-induced corticosterone level, while there was not a significant correlation with anxiety-like behavior. Overall, our results suggest preserved but blunted hippocampal structural plasticity in MS rats that is not sufficient to compensate for hippocampal dysfunction and hypersensitivity to CRS.