Eisinger Brian E, Driessen Terri M, Zhao Changjiu, Gammie Stephen C
Department of Zoology, University of Wisconsin-Madison Madison, WI, USA.
Department of Zoology, University of Wisconsin-Madison Madison, WI, USA ; Neuroscience Training Program, University of Wisconsin-Madison Madison, WI, USA.
Front Behav Neurosci. 2014 Apr 2;8:110. doi: 10.3389/fnbeh.2014.00110. eCollection 2014.
The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for post-partum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for post-partum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Post-partum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum (LS) and medial preoptic area (MPOA), enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for post-partum psychosis with aspects of schizophrenia and BPD.
向母亲角色的转变涉及中枢神经系统的变化，这些变化会改变社交能力和情感状态。然而，这些变化也使女性面临产后抑郁和精神病的风险，这会损害育儿能力并对孩子产生不利影响。因此，核心基因子集的表达和相互作用的变化可能对健康母亲表型的出现至关重要，但相同基因的不适当变化可能使女性面临产后疾病的风险。本研究评估了内侧前额叶皮质（mPFC）中的基因芯片表达变化，该区域与母性行为和精神疾病均有关联。将产后小鼠与与雌性一起饲养并隔离相同时间的未生育对照小鼠进行比较。使用模块化单集富集测试（MSET），我们发现母体mPFC的基因格局与精神分裂症相关基因数据库（5组中的5组）和双相情感障碍（BPD，3组中的3组）具有统计学相似性。与先前对母体外侧隔区（LS）和内侧视前区（MPOA）的研究不同，自闭症和抑郁症相关基因的富集并不显著（9组中的2组，4组中的0组）。与多种疾病相关的基因包括脂肪酸结合蛋白7（Fabp7）、代谢型谷氨酸受体3（Grm3）、血小板衍生生长因子β多肽（Pdgfrb）和核受体亚家族1 D组成员1（Nr1d1）。逆转录定量聚合酶链反应（RT-qPCR）证实了这些基因变化以及FMS样酪氨酸激酶1（Flt1）和脑啡肽原（Penk）的变化。系统水平的方法揭示了发育基因网络在建立母体表型中的作用，并间接表明许多微小RNA和转录因子在介导表达变化中发挥作用。总之，本研究表明，参与塑造健康母体大脑的一部分基因在精神健康障碍中也可能失调，使女性面临产后精神病的风险，且具有精神分裂症和双相情感障碍的某些特征。
