非表示:
キーワード:
Match/mismatch, stress, behavior, glucocorticoid receptor, Fkbp51
要旨:
Chronic stress is a major risk factor for depression. Interestingly, not
all individuals develop psychopathology after chronic stress exposure.
In contrast to the prevailing view that stress effects are cumulative
and increase stress vulnerability throughout life, the match/mismatch
hypothesis of psychiatric disorders. The match/mismatch hypothesis
proposes that individuals who experience moderate levels of early life
psychosocial stress can acquire resilience to renewed stress exposure
later in life. Here, we have tested this hypothesis by comparing the
developmental effects of 2 opposite early life conditions, when followed
by 2 opposite adult environments. Male Balb/c mice were exposed to
either adverse early life conditions (limited nesting and bedding
material) or a supportive rearing environment (early handling). At
adulthood, the animals of each group were either housed with an
ovariectomized female (supportive environment) or underwent chronic
social defeat stress (socially adverse environment) for 3 weeks. At the
end of the adult manipulations, all of the animals were returned to
standard housing conditions. Then, we compared the neuroendocrine,
behavioral and molecular effects of the interaction between early and
adult environment. Our study shows that early life adversity does not
necessarily result in increased vulnerability to stress. Specific
endophenotypes, like hypothalamic-pituitary-adrenal axis activity,
anxiety-related behavior and glucocorticoid receptor expression levels
in the hippocampus were not significantly altered when adversity is
experienced during early life and in adulthood, and are mainly affected
by either early life or adult life adversity alone. Overall our data
support the notion that being raised in a stressful environment prepares
the offspring to better cope with a challenging adult environment and
emphasize the role of early life experiences in shaping adult
responsiveness to stress.
