Effects of maternal separation on dynamics of urocortin 1 and brain-derived neurotrophic factor in the rat non-preganglionic Edinger-Westphal nucleus

Balázs Gaszner, Kai Ole Jensen, József Farkas, Dóra Reglodi, Valér Csernus, Eric W. Roubos, Tamas Kozicz

Research output: Contribution to journalArticle

26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)439-451
Number of pages13
JournalInternational Journal of Developmental Neuroscience
Issue number5
StatePublished - Aug 1 2009
Externally publishedYes



  • Acute restraint stress
  • BDNF
  • c-Fos
  • Corticosterone
  • Triple immunofluorescence immunocytochemistry
  • Ucn1

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this