Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/29144
Title
Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development
File
Description

Abstract

It is widely accepted that maternal separation (MS) induces stress in children and disrupts neural circuit formation during early brain development. Even though such disruption occurs transiently early in life, its influence persists after maturation, and could lead to various neurodevelopmental disorders. Our recent study revealed that repeated MS reduces the number of inhibitory neurons and synapses in the medial prefrontal cortex (mPFC) and causes mPFC-related social deficits after maturation. However, how MS impedes mPFC development during early brain development remains poorly understood. Here, we focused on brain-derived neurotrophic factor (BDNF) involved in the development of inhibitory neurons, and examined time-dependent BDNF expression in the mPFC during the pre-weaning period in male rats exposed to MS. Our results show that MS attenuates BDNF expression only around the end of the first postnatal week. Likewise, mRNA expression of activity-regulated cytoskeleton-associated protein (Arc), an immediate-early gene whose expression is partly regulated by BDNF, also decreased in the MS group along with the reduction in BDNF expression. On the contrary, mRNA expression of tropomyosin-related kinase B (TrkB), which is a BDNF receptor, was scarcely altered, while its protein expression decreased in the MS group only during the weaning period. In addition, MS reduced mRNA levels of glutamic acid decarboxylase (GAD) 65, a GABA synthesizing enzyme, only during the weaning period. Our results suggest that repeated MS temporarily attenuates BDNF signaling in the mPFC during early brain development. BDNF plays a crucial role in the development of inhibitory neurons; therefore, transient attenuation of BDNF signaling may cause delays in GABAergic neuron development in the mPFC.

Keywords:

Brain-derived neurotrophic factor; Cellular neuroscience; Early brain development; GABAergic neuron; Maternal separation; Medial prefrontal cortex; Mental disorder; Molecular neuroscience; Nervous system; Systems neuroscience

(医博甲761)

Author
著者 天雲 千晶
著者(ヨミ) テンクモ チアキ
著者(別表記) Chiaki Tenkumo
Publication Title
Heliyon
Publication Title Alternative
Heliyon.
Volume
6
Issue
8
Start Page
e04781
End Page
e04781
Publisher
Elsevier
Published Date
2020-08-26
ISSN
2405-8440
PMID
32923721
DOI
10.1016/j.heliyon.2020.e04781
Resource Type
Thesis or Dissertation
Language
eng
Rights
Copyright © 2020 The Authors.
This is the Publisher's Version of the following article: Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development; Heliyon; Volume 6 Issue 8 (2020) article number: e04781; doi: 10.1016/j.heliyon.2020.e04781 , which has been published in final form at https://doi.org/10.1016/j.heliyon.2020.e04781 .
この博士論文の本文については、次のエルゼビアの著作権ポリシーの規定により公開しています。「博士論文の場合は、エンバーゴ期間に関係なく機関リポジトリに出版社版を公開することができます。」 The text of this doctoral dissertation is published according to the following Elsevier copyright policy. "In the case of doctoral dissertations, publishers can be published in institutional repositories regardless of the Embargo period."
Text Version
ETD
Grant ID
博甲第761号
Grant Date
2020-12-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.