TY - JOUR
T1 - Effects of maternal separation on dynamics of urocortin 1 and brain-derived neurotrophic factor in the rat non-preganglionic Edinger-Westphal nucleus
AU - Gaszner, Balázs
AU - Jensen, Kai Ole
AU - Farkas, József
AU - Reglodi, Dóra
AU - Csernus, Valér
AU - Roubos, Eric W.
AU - Kozicz, Tamás
N1 - Funding Information:
This work was supported by The Netherlands Organization for Scientific Research, NWO; Grant number: 864.05.008 (to T.K.), by the 6th FP of the EU “Marie Curie Host Fellowships for Early Stage Research Training” EURON MEST-CT-2005-020589 (to B.G.), and by the Medical Scientific Council in Hungary; ETT 439/2006 (to D.R.).
PY - 2009/8
Y1 - 2009/8
N2 - Although mood disorders are frequently genetically determined and to some degree gender-dependent, the concept of early life 'programming', implying a relation between perinatal environmental events and adult mood disorders, has recently gained considerable attention. In particular, maternal separation (MS) markedly affects various stress-sensitive brain centers. Therefore, MS is considered as a suitable experimental paradigm to study how early life events affect brain plasticity and, hence, cause psychopathologies like major depression. In adult mammals, the classical hypothalamo-pituitary-adrenal (HPA-) axis and the urocortin 1 (Ucn1)-containing non-preganglionic Edinger-Westphal nucleus (npEW) respond in opposite ways to chronic stressors. This raises the hypothesis that MS, which is known to increase vulnerability for adult mood disorders via the dysregulation of the HPA-axis, will affect npEW dynamics as well. We have tested this hypothesis and, moreover, studied a possible role of brain-derived neurotrophic factor (BDNF) in such npEW plasticity. By triple immunocytochemistry we show that BDNF and Ucn1 coexist in rat npEW-neurons that are c-Fos-positive upon acute stress. Quantitative immunocytochemistry revealed that MS increases the contents of Ucn1 and BDNF in these cells. Furthermore, in males and females, the c-Fos response of npEW-Ucn1 neurons upon restraint stress was blunted in animals with MS history, a phenomenon that was concomitant with dampening of the HPA corticosterone response in females but not in males. Based on these data we suggest that the BDNF-containing npEW-Ucn1 system might be affected by MS in a sex-specific manner. This supports the idea that the npEW would play a role in the appearance of sex differences in the pathogenesis of stress-induced mood disorders.
AB - Although mood disorders are frequently genetically determined and to some degree gender-dependent, the concept of early life 'programming', implying a relation between perinatal environmental events and adult mood disorders, has recently gained considerable attention. In particular, maternal separation (MS) markedly affects various stress-sensitive brain centers. Therefore, MS is considered as a suitable experimental paradigm to study how early life events affect brain plasticity and, hence, cause psychopathologies like major depression. In adult mammals, the classical hypothalamo-pituitary-adrenal (HPA-) axis and the urocortin 1 (Ucn1)-containing non-preganglionic Edinger-Westphal nucleus (npEW) respond in opposite ways to chronic stressors. This raises the hypothesis that MS, which is known to increase vulnerability for adult mood disorders via the dysregulation of the HPA-axis, will affect npEW dynamics as well. We have tested this hypothesis and, moreover, studied a possible role of brain-derived neurotrophic factor (BDNF) in such npEW plasticity. By triple immunocytochemistry we show that BDNF and Ucn1 coexist in rat npEW-neurons that are c-Fos-positive upon acute stress. Quantitative immunocytochemistry revealed that MS increases the contents of Ucn1 and BDNF in these cells. Furthermore, in males and females, the c-Fos response of npEW-Ucn1 neurons upon restraint stress was blunted in animals with MS history, a phenomenon that was concomitant with dampening of the HPA corticosterone response in females but not in males. Based on these data we suggest that the BDNF-containing npEW-Ucn1 system might be affected by MS in a sex-specific manner. This supports the idea that the npEW would play a role in the appearance of sex differences in the pathogenesis of stress-induced mood disorders.
KW - Acute restraint stress
KW - BDNF
KW - Corticosterone
KW - Triple immunofluorescence immunocytochemistry
KW - Ucn1
KW - c-Fos
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U2 - 10.1016/j.ijdevneu.2009.05.006
DO - 10.1016/j.ijdevneu.2009.05.006
M3 - Article
C2 - 19460425
AN - SCOPUS:67349089843
SN - 0736-5748
VL - 27
SP - 439
EP - 451
JO - International Journal of Developmental Neuroscience
JF - International Journal of Developmental Neuroscience
IS - 5
ER -