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Prolonged maternal separation attenuates BDNF‐ERK signaling correlated with spine formation in the hippocampus during early brain development
Author(s) -
Ohta Kenichi,
Suzuki Shingo,
Warita Katsuhiko,
Kaji Tomohiro,
Kusaka Takashi,
Miki Takanori
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13977
Subject(s) - synaptogenesis , hippocampal formation , hippocampus , mapk/erk pathway , neurotrophic factors , dendritic spine , brain derived neurotrophic factor , neuroscience , signal transduction , tropomyosin receptor kinase b , biology , medicine , offspring , synaptic plasticity , microbiology and biotechnology , endocrinology , receptor , genetics , pregnancy
Maternal separation ( MS ) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS , and focused on brain‐derived neurotrophic factor ( BDNF ) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days ( PD ) 2–20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal‐regulated kinase ( ERK ) around PD 7. Moreover, plasticity‐related immediate early genes, which are transcriptionally regulated by BDNF ‐ ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 ( CA 1) of hippocampus at PD 7. Considering that BDNF ‐ ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA 1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF ‐ ERK signaling during primary synaptogenesis with a region‐specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA 1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood.