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キーワード:
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要旨:
During the early postnatal period, environmental influences play a
pivotal role in shaping the development of the neocortex, including the
prefrontal cortex (PFC) that is crucial for working memory and
goal-directed actions. Exposure to stressful experiences during this
critical period may disrupt the development of PFC pyramidal neurons and
impair the wiring and function of related neural circuits. However, the
molecular mechanisms of the impact of early-life stress on PFC
development and function are not well understood. In this study, we
found that repeated stress exposure during the first postnatal week
hampered dendritic development in layers II/III and V pyramidal neurons
in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL)
of neonatal mice. The deleterious effects of early postnatal stress on
structural plasticity persisted to adulthood only in ACd layer V
pyramidal neurons. Most importantly, concurrent blockade of
corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin
administration (20 mu g/g of body weight) during early-life stress
exposure prevented stress-induced apical dendritic retraction and spine
loss in ACd layer V neurons and impairments in PFC-dependent cognitive
tasks. Moreover, the magnitude of dendritic regression, especially the
shrinkage of apical branches, of ACd layer V neurons predicted the
degree of cognitive deficits in stressed mice. Our data highlight the
region-specific effects of early postnatal stress on the structural
plasticity of prefrontal pyramidal neurons, and suggest a critical role
of CRF1 in modulating early-life stress-induced prefrontal
abnormalities.
