AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, cilt.302, sa.7, 2012 (SCI-Expanded)
Exposure to early life
stress causes increased stress responsiveness and permanent changes
in the central nervous system. We recently showed that delayed
gastric emptying (GE) and accelerated colonic transit (CT) in response
to acute restraint stress (ARS) were completely restored
following chronic homotypic stress (CHS) in rats via upregulation of
hypothalamic oxytocin (OXT) expression. However, it is unknown
whether early life stress affects hypothalamic OXT circuits and
gastrointestinal motor function. Neonatal rats were subjected to maternal
separation (MS) for 180 min/day for 2 wk. Anxiety-like
behaviors were evaluated by the elevated-plus-maze test. GE and CT
were measured under nonstressed (NS), ARS, and CHS conditions.
Expression of corticotropin-releasing factor (CRF) and OXT in the
paraventricular nucleus (PVN) of the hypothalamus was evaluated by
real time RT-PCR and immunohistochemistry. MS increased anxietylike
behaviors. ARS delayed GE and accelerated CT in control and
MS rats. After CHS, delayed GE and accelerated CT were restored in
control, but not MS, rats. CRF mRNA expression was significantly
increased in response to ARS in control and MS rats. Increased CRF
mRNA expression was still observed following CHS in MS, but not
control, rats. In response to CHS, OXT mRNA expression was
significantly increased in control, but not MS, rats. The number of
OXT-immunoreactive cells was increased following CHS in the
magnocellular part of the PVN in control, but not MS, rats. MS
impairs the adaptation response of gastrointestinal motility following
CHS. The mechanism of the impaired adaptation involves downregulation
of OXT and upregulation of CRF in the hypothalamus in MS
rats.