Miyata Shigeo, Kurachi Masashi, Sakurai Noriko, Yanagawa Yuchio, Ishizaki Yasuki, Mikuni Masahiko, Fukuda Masato
Department of Psychiatry and Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan; Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan.
Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Heliyon. 2016 Dec 22;2(12):e00219. doi: 10.1016/j.heliyon.2016.e00222. eCollection 2016 Dec.
The prevalence of major depressive disorder (MDD) is higher in women than in men, and this may be due to the decline in estrogen levels that occurs during the menopausal transition. We studied the biological alterations in the medial prefrontal cortex (mPFC), which is a region that is highly implicated in the neurobiology of MDD, and the blood cells (BCs) of ovariectomized (OVX) mice subjected to chronic mild stress (CMS), which represents a mouse model of depression during menopause.
The mPFC and the BCs were obtained from the same individuals. Gene expression levels were analyzed by microarray. The data were used for the Ingenuity Pathway Analysis and the Gene Ontology analysis.
The gene expression alterations (GEAs) induced by OVX were mainly associated with ribosomal and mitochondrial functions in both the mPFC and the BCs. Rapamycin-insensitive companion of mTOR (RICTOR) was identified as a possible upstream regulator of the OVX-induced GEAs in both tissues. The CMS-induced GEAs were associated with retinoic acid receptor signaling, inflammatory cytokines and post-synaptic density in the mPFC, but not in the BCs.
OVX and CMS independently affect biological pathways in the mPFC, which is involved in the development of the depression-like phenotype. Because a subset of the OVX-induced GEAs in the mPFC also occurred in the BCs, the GEAs in the BCs might be a useful probe to predict biological pathways in the corresponding brain tissue under specific conditions such as OVX in females.
重度抑郁症（MDD）在女性中的患病率高于男性，这可能是由于绝经过渡期间雌激素水平下降所致。我们研究了内侧前额叶皮质（mPFC）的生物学改变，该区域与MDD的神经生物学高度相关，还研究了接受慢性轻度应激（CMS）的去卵巢（OVX）小鼠的血细胞（BCs），CMS代表绝经期间抑郁症的小鼠模型。
mPFC和BCs取自同一批个体。通过微阵列分析基因表达水平。这些数据用于 Ingenuity 通路分析和基因本体分析。
OVX诱导的基因表达改变（GEAs）主要与mPFC和BCs中的核糖体及线粒体功能相关。mTOR的雷帕霉素不敏感伴侣（RICTOR）被确定为两种组织中OVX诱导的GEAs的可能上游调节因子。CMS诱导的GEAs与mPFC中的视黄酸受体信号传导、炎性细胞因子和突触后密度相关，但与BCs无关。
OVX和CMS独立影响mPFC中的生物学通路，mPFC参与了抑郁样表型的发展。由于mPFC中OVX诱导的部分GEAs也出现在BCs中，因此BCs中的GEAs可能是预测女性在OVX等特定条件下相应脑组织生物学通路的有用探针。
