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

Abstract

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.

Urocortin‐expressing olivocochlear neurons exhibit tonotopic and developmental changes in the auditory brainstem and in the innervation of the cochlea

“…Urocortin-IR reveals a topographic gradient for a stress-related subpopulation of cholinergic neurons in the adult LSO Consistent with previously published data from mouse (Vetter et al, 2002;Wang et al, 2002) and rat (Bittencourt et al, 1999;Wang et al, 2002;Gaszner et al, 2009), our Ucn immunostaining of transversal sections from adult gerbil brainstem revealed typical Ucn-IR in the non-preganglionic part of the Edinger-Westphal nucleus (Fig. 1A) and in the LSO (Fig.…”

“…In the rat and the cebus monkey, Ucn staining of cells was confirmed with Ucn mRNA expression (Bittencourt et al, 1999;Vasconcelos et al, 2003). In our study the pattern of immunostaining in neurons of the Edinger-Westphal nucleus, which is generally accepted as a reference nucleus for Ucn, was identical to recently published staining data in rat, mouse, ferret, monkey, and human (Vasconcelos et al, 2003;Horn et al, 2008Horn et al, , 2009Gaszner et al, 2009).…”

MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression

“…27,28 Sections were washed 3 times for 10 min in 0.1 M of PBS followed by incubation in 0.1% Triton X-100 in PBS for 30 min. Next, sections were incubated overnight at 4°C with the primary antibody Ucn1 anti-rabbit (gift from W.W. Vale, Salk Institute) at a 1:5000 dilution, with 2% normal donkey serum (Jackson Immunoresearch) in PBS.…”

Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers

“…The experiment was 240 carried out exactly as published earlier (Gaszner et al,241 2012), except that mice of the control group were tested 242 10 days before perfusion in order to avoid that the acute 243 effects of forced swim influence our controls. To avoid 244 possible chronic effects we exposed the mice to one swim (Gaszner et al, 2004(Gaszner et al, , 2009 Snedecor and Cochran, 1989). Outlier data 498 beyond the two sigma range were excluded from statis- In non-injected mice, both stress (F 3,22 Periaqueductal gray matter.…”