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

( 最大 2000 件 )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/29144
タイトル
Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development
ファイル
内容記述

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)

著者
著者 天雲 千晶
著者(ヨミ) テンクモ チアキ
著者(別表記) Chiaki Tenkumo
掲載誌
Heliyon
掲載誌(別表記)
Heliyon.
6
8
開始ページ
e04781
終了ページ
e04781
出版者
Elsevier
出版年月日
2020-08-26
ISSN
2405-8440
PMID
32923721
DOI
10.1016/j.heliyon.2020.e04781
資料タイプ
学位論文
言語
英語
権利関係
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."
博士論文(全文を含む)
学位授与番号
博甲第761号
学位授与年月日
2020-12-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.