Blunted amygdalar anti-inflammatory cytokine effector response to postnatal stress in prenatally stressed rats.
Smad1 is the downstream effector for bone morphogenetic protein, part of the anti-inflammatory cytokine family. Glucocorticoids (GCs) increase the production of anti-inflammatory cytokines to oppose the actions of pro-inflammatory cytokines. Here we used the prenatally stressed (PS) rat to see if chronic GC activation affects this protective mechanism in the amygdala. Male PS and control offspring were either left undisturbed or exposed to a 2-week regimen of intruder stress. One week later, half of these animals were further subjected to restraint stress for 3 days. Nuclear and cytoplasmic phosphorylated (p)-Smad1 were visualized by immunocytochemistry and quantified in the lateral and basolateral amygdala and in the hind limb primary somatosensory (S1HL) cortex. PS rats showed significantly greater baseline p-Smad1 per cell than controls. However, intruder stress increased p-Smad1 nuclear staining in the control rats only: no further increases in either compartment were observed in the PS group. With repeated restraint stress, attenuation of both cytoplasmic and nuclear p-Smad1 responses was significantly greater in controls. Thus, the overall p-Smad1 responsiveness of amygdala neurons of PS rats to life stressors is blunted. We hypothesize that the amygdala may play an essential role in initiating the cytokine response to stress in the adult rat brain. Basal p-Smad1 staining was unaffected by prenatal stress in the S1HL cortex but became elevated in the cytoplasm following intruder stress. The significance of this is unknown, but may point to a means by which stress can generally affect cells whose functions are unrelated to driving the sympathoadrenal system.
Kaur
Gurjinder
G
Department of Neurobiology and Anatomy, West Virginia University School of Medicine, WV 26506-9128, USA. gkaur@nki.rfmh.org
Salm
A K
AK
D000679:Amygdala / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005938:Glucocorticoids; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051898:Smad1 Protein / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology*
D005904:Glial Fibrillary Acidic Protein; D005938:Glucocorticoids; D051898:Smad1 Protein; C497400:Smad1 protein, rat