AUTHOR=Eisinger Brian E., Driessen Terri M., Zhao Changjiu , Gammie Stephen 

TITLE=Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2014.00110

DOI=10.3389/fnbeh.2014.00110

ISSN=1662-5153

ABSTRACT=<p>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 (<italic>Fabp7</italic>), glutamate metabotropic receptor 3 (<italic>Grm3</italic>), platelet derived growth factor, beta polypeptide (<italic>Pdgfrb</italic>), and nuclear receptor subfamily 1, group D, member 1 (<italic>Nr1d1</italic>). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (<italic>Flt1</italic>) and proenkephalin (<italic>Penk</italic>). 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.</p>