Bacterial infection early in life protects against stressor-induced depressive-like symptoms in adult rats.
Both early-life stress and immune system activation in adulthood have been linked independently to depression in a number of studies. However, the relationship between early-life infection, which may be considered a "stressor", and later-life depression has not been explored. We have reported that neonatal bacterial infection in rats leads to exaggerated brain cytokine production, as well as memory impairments, to a subsequent peripheral immune challenge in adulthood, and therefore predicted that stressor-induced depressive-like symptoms would be more severe in these rats as well. Rats treated on postnatal day 4 with PBS or Escherichia coli were as adults exposed to inescapable tailshock stress (IS), and then tested for sucrose preference, social exploration with a juvenile, and overall activity, 1, 3, 5, and 7 days following the stressor. Serum corticosterone and extracellular 5-HT within the basolateral amygdala were measured in a second group of rats in response to the IS. IS resulted in profound depressive-like behaviors in adult rats, but, surprisingly, rats that suffered a bacterial infection early in life had blunted corticosterone responses to the stressor and were remarkably protected from the depressive symptoms compared to controls. These data suggest that early-life infection should be considered within a cost/benefit perspective, in which outcomes in adulthood may be differentially protected or impaired. These data also suggest that the immune system likely plays a previously unsuspected role in "homeostatic" HPA programming and brain development, which may ultimately lend insight into the often-contradictory literature on cytokines, inflammation, and depression.
Bilbo
Staci D
SD
Department of Psychology and Neuroscience, Duke University, Durham, NC 27708, USA. staci.bilbo@duke.edu
Yirmiya
Raz
R
Amat
Jose
J
Paul
Evan D
ED
Watkins
Linda R
LR
Maier
Steven F
SF
D000818:Animals; D000831:Animals, Newborn; D001424:Bacterial Infections / Q000523:psychology*; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000517:prevention & control* / Q000523:psychology*; D004597:Electroshock; D004927:Escherichia coli Infections / Q000523:psychology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000523:psychology*; D013395:Sucrose / Q000494:pharmacology; D013649:Taste / Q000187:drug effects
D012701:Serotonin; D013395:Sucrose; D003345:Corticosterone