Influence of prenatal stress on behavioral, endocrine, and cytokine responses to adulthood bacterial endotoxin exposure

Prior research suggests that prenatal stress, among other effects, can lead to hyper-reactivity of the offspring's hypothalamic-pituitary-adrenal (HPA) axis and alterations in immune function. These stress-induced changes have been linked to a greater propensity to develop depression or anxiety disorders. Furthermore, prenatally stressed offspring may be more susceptible to certain diseases. The immune alterations induced by prenatal stress exposure may disrupt the normal communication between the immune system, endocrine system, and central nervous system, potentially making prenatally stressed individuals more vulnerable to the negative aspects of immune activation, including cytokine-induced cognitive deficits and anxiety. The present study investigated whether prenatal stress would exaggerate these detrimental effects of peripheral immune activation. We hypothesized that prenatally stressed subjects would be hypersensitive to endotoxin administration and would therefore show exaggerated learning deficits, increased anxiety-like behavior, and increased peripheral and central interleukin-1beta (IL-1beta) levels. The observed results only partially supported our hypotheses, as prenatally stressed subjects showed evidence, albeit modest, of increased anxiety-like behavior following endotoxin administration relative to non-stressed controls. While prenatal stress exposure or lipopolysaccharide (LPS) administration independently impaired learning, the data failed to support the hypothesis that prenatally stressed subjects would show exaggerated cognitive deficits, engendered via enhanced peripheral and central IL-1beta levels, following immune activation. Collectively, the data suggest that although prenatal stress exposure led to increases in anxiety-like behavior following endotoxin exposure, it did not appear to increase susceptibility to LPS-induced cognitive decline or elevations in proinflammatory cytokine production.

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