Download Mousia (EFET): Corticosterone-regulated actions in the rat

Parma: 29-30 October 2012
Neuroscience 167, (2010) 741-749
Bisphenol A
The Aim
The aim of this study was:
- to investigate in the rat the possible organizational effects of low
BPA
perinatal
exposure,
to
glucocorticoid-regulated
responses.
Plasma corticosterone levels and the two types of hippocampal
corticosteroid receptors (MR and GR) were determined in midadolescence offspring under basal conditions and following a Y-maze
task.
Hippothalamic – Pituitary – Adrenal
Axis
Hippocampus
- GR
Hypothalamus
- GR
Stage 1: alarm reaction The first stage of the general adaptation stage,
the alarm reaction, is the immediate reaction to a stressor. In the initial
phase of stress, humans exhibit a "fight or flight" response, which
prepares the body for physical activity.
Stage 2: stage of resistance might also be named the stage of
adaptation, instead of the stage of resistance. During this phase, if
the stress continues, the body adapts to the stressors it is exposed
to. Changes at many levels take place in order to reduce the effect
of the stressor.
- GR
Pituitary
adrenals
GR in the hippocampus mediate the negative
Glucocorticoids
CRH
Stage 3: stage of exhaustion At this stage, the stress has continued for
some time. The body's resistance to the stress may gradually be
reduced, or may collapse quickly.
Corticotropin-Releasing Hormone
ACTH Adrenocorticotropic hormone
AVP Arginine vasopressin
feedback of corticosterone.
Experimental Procedures
•
•
Female Wistar breeders were exposed to BPA (40 μg/kg provided through
food; Sigma-Aldrich, USA) from the beginning of pregnancy to the end of
lactation.
At puberty, half of the offspring (both sexes) were sacrificed under basal
conditions and the rest were subjected to a spatial learning task (Y-maze)
prior to sacrifice.
•Y-maze task (PND 46)
•Trial 1 (5min acquisition)
•Trial 2 (recall or memory test,
scored 1 and 5 min ) - 4 h later
Results
•
BASAL CONDITIONS
 BPA treated females had higher corticosterone levels than control
females and BPA males.
 BPA treated females had lower GR levels in the hippocampus than
BPA males, while no sex difference was observed in the control
offspring.
 No effect of BPA was observed in MR levels.
•
Y-maze TEST (mildly stressful conditions)
 Corticosterone levels were increased in BPA treated animals of
both sexes, compared to the controls.
BPA treatment & gender significantly interacted in modifying basal corticosterone levels.
a.
Corticosterone levels were higher in BPA treated females compared to control females and BPA treated males.
b.
Significant effect of sex on GR levels. GR receptor levels were lower in BPA treated females versus males. No
sex difference were observed in the GR levels of the control animals.
c.
MR levels were not affected by the gender or BPA treatment.
 Effect of perinatal BPA treatment and sex on basal plasma corticosterone and hippocampal glucocorticoid receptor
(GR) and mineralocorticoid receptor (MR).
(#) denotes significant effect of BPA treatment
($) denotes significant effect of sex
 Representative Western blot autoradiograms for GR, MR and GAPDH (normalization protein) are also provided.
BPA exposure significantly reduced animals’ general motivation for exploration
during the Y-maze test, the effect being more pronounced in females.
Effect of perinatal BPA treatment and sex on the animals’ general exploration attitude, as measured by total
number of entries during the Y-maze task.
-
(#) significant effect of BPA treatment
-
($) significant effect of sex
The results showed that BPA decreased the explorative behaviour - as assessed by the number of entries - mainly in female
BPA offsprings (trial 1). Also the exploration strategy of BPA female offsprings (avoidance of the centre and preference for the
familiar arms, in combination with the severely reduced exploration attitude (reduced number of entries) suggests ‘increased
anxiety’. Furthermore this anxiety-like behaviour of BPA females is supported by their elevated corticosterone levels at
basal conditions.
BPA treatment significantly increased plasma corticosterone levels in female
offspring comparing to controls both under basal conditions and following Y-maze.
Effect of perinatal BPA treatment, sex and Y-maze experience on plasma corticosterone levels of mid-adolescent
rats. Corticosterone was determined either under basal conditions or immediately following the Y-maze task.
(#) denotes the effect of BPA treatment, as compared to the control of the same sex and the Y-maze experience
($) denotes the effect of sex, as compared to the same treatment
(‡) denotes the effect of Y-maze experience, as compared to the same sex and treatment group under basal conditions.
Discussion of Results & Conclusions
Main findings:
a. BPA can induce sex-dependent alterations on basal corticosterone levels and
augment corticosterone rise following a spatial task/mild stress,
b. affect GR levels in the hippocampus of adolescent females,
c. impair spatial recognition memory in both sexes,
d. modify in a sexually dimorphic manner the animals’ exploration attitude and
strategy to resolve the task.

The above findings are evidences that the BPA can program molecular components of the stress
response system.

The increased basal corticosterone levels detected in BPA treated females could be attributed to the
estrogen-mimicking action of this compound on the adrenals, towards increased corticosteroid
synthesis.

The study suggests that the prolonged high corticosterone levels of BPA females led to impaired acquisition of
information and memory formation (during trial 1) and memory recall.

The estrogen-like action of BPA treated females may explain the reduced GR levels resulting in an activated HPA axis
under basal conditions thus reduced efficacy to terminate a subsequent stress response.

The increased GR levels 4 hours following the mild stress/learning task imply an increased plasticity of
the adolescent hippocampus to compensate axis activation.