Developmental exposure to corticosterone: behavioral changes and differential effects on leukemia inhibitory factor (LIF) and corticotropin-releasing hormone (CRH) gene expression in the mouse.
BACKGROUND
Cytokines are found in both the peripheral and central nervous system. There has been increasing interest in their potential role in some of the behavioral features of depressive disorders. Leukemia inhibitory factor (LIF), a proinflammatory cytokine, produces stimulation of adrenocorticotropic hormone (ACTH) secretion in response to emotional and inflammatory stress and recently has been linked to depressive-type behavior. Both the hypothalamic-pituitary-adrenal axis and the immune system, including cytokine-mediated responses, appear to be susceptible to long-term programming during fetal and neonatal development.


OBJECTIVE
The present study was designed to characterize the effects of perinatal exposure to corticostereone on behavior, hypothalamic LIF and corticotropin-releasing hormone (CRH) mRNA expression, and basal plasma corticosterone levels in adult female mice.


METHODS
Corticosterone was added to the drinking water beginning the last week of gestation and continued until weaning. Behavior in the open field and forced swim tests, baseline plasma corticosterone levels, and hypothalamic LIF and CRH gene expression were evaluated in the adult offspring.


RESULTS
Mice exposed to perinatal corticosterone showed increased immobility in the forced swim test and increased locomotor activity in the open field test. Although there were no differences between treatment groups in terms of basal plasma levels of corticosterone or hypothalamic CRH mRNA, LIF mRNA expression was increased in the hypothalamus.


CONCLUSIONS
These results show that perinatal exposure to glucocorticoids can produce long-term behavioral changes and upregulation of central LIF mRNA expression.
Pechnick
Robert N
RN
Department of Psychiatry and Mental Health, Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA. pechnickr@cshs.org
Kariagina
Anastasia
A
Hartvig
Evelyn
E
Bresee
Catherine J
CJ
Poland
Russell E
RE
Chesnokova
Vera M
VM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D053605:Leukemia Inhibitory Factor; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone