Abstract:
:Deprivation of maternal care during early development markedly affects emotional development, but the underlying neuromolecular mechanisms are not fully understood. In a mouse model of disrupted mother-infant relationship, early weaning causes long-term impacts on pups to exhibit increased corticosterone secretion, anxiety, and stress responses in their adulthood. Revealing the molecular mechanisms behind it would beneficial to ameliorating mental problems caused by abuse in childhood. We report that normalizing circulating corticosterone in early-weaned mice, either in adulthood or soon after weaning, ameliorated anxiety levels assessed in the plus maze test. Administering a glucocorticoid receptor antagonist into the prefrontal cortex (PFC) reversed the effects of early weaning, whereas administering corticosterone increased anxiety levels, suggesting that the PFC is corticosterone's target brain region. In the PFCs of early-weaned mice, we observed prolonged reductions in the expression of brain-derived neurotrophic factor (BDNF) and associated mRNAs. Anxiety in early-weaned mice was ameliorated by pretreatment with BDNF or a BDNF receptor agonist. In summary, early weaning increased anxiety levels by modulating glucocorticoid and BDNF signaling in the PFC.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Kikusui T,Kanbara N,Ozaki M,Hirayama N,Ida K,Tokita M,Tanabe N,Mitsuyama K,Abe H,Yoshida M,Nagasawa M,Mogi Kdoi
10.1038/s41598-019-40530-9subject
Has Abstractpub_date
2019-03-08 00:00:00pages
3991issue
1issn
2045-2322pii
10.1038/s41598-019-40530-9journal_volume
9pub_type
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