Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

Abstract

Major depressive disorder (MDD) is a prevalent, chronic, and relapse-prone psychiatric disease. However, the intermediate molecules resulting from stress and neurological impairment in different brain regions are still unclear. To clarify the pathological changes in the dentate gyrus (DG) and anterior cingulate cortex (ACC) regions of the MDD brain, which are the most closely related to the disease, we investigated the published microarray profile dataset GSE84183 to identify unpredictable chronic mild stress- (UCMS-) induced differentially expressed genes (DEGs) in the DG and ACC regions. Based on the DEG data, functional annotation, protein-protein interaction, and transcription factor (TF) analyses were performed. In this study, 1071 DEGs (679 upregulated and 392 downregulated) and 410 DEGs (222 upregulated and 188 downregulated) were identified in DG and ACC, respectively. The pathways and GO terms enriched by the DEGs in the DG, such as cell adhesion, proteolysis, ion transport, transmembrane transport, chemical synaptic transmission, immune system processes, response to lipopolysaccharide, and nervous system development, may reveal the molecular mechanism of MDD. However, the DEGs in the ACC involved metabolic processes, proteolysis, visual learning, DNA methylation, innate immune responses, cell migration, and circadian rhythm. Sixteen hub genes in the DG (Fn1, Col1a1, Anxa1, Penk, Ptgs2, Cdh1, Timp1, Vim, Rpl30, Rps21, Dntt, Ptk2b, Jun, Avp, Slit1, and Sema5a) were identified. Eight hub genes in the ACC (Prkcg, Grin1, Syngap1, Rrp9, Grwd1, Pik3r1, Hnrnpc, and Prpf40a) were identified. In addition, eleven TFs (Chd2, Zmiz1, Myb, Etv4, Rela, Tcf4, Tcf12, Chd1, Mef2a, Ubtf, and Mxi1) were predicted to regulate more than two of these hub genes. The expression levels of ten randomly selected hub genes that were specifically differentially expressed in the MDD-like animal model were verified in the corresponding regions in the human brain. These hub genes and TFs may be regarded as potential targets for future MDD treatment strategies, thus aiding in the development of new therapeutic approaches to MDD.

Abnormal Reginal Homogeneity in Left Anterior Cingulum Cortex and Precentral Gyrus as a Potential Neuroimaging Biomarker for First-Episode Major Depressive Disorder

“…Anterior cerebrum The ACC is the first half of the cingulum gyrus, which is closely related to human cognitive execution, emotional processing, and other brain functions ( 34 ). When ACC is damaged, it will produce many clinical symptoms, including inattention, dysfunction of autonomic function regulation, emotional instability ( 35 , 36 ). Studies have found that the ACC is prone to damage in depression ( 37 , 38 ).…”

Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability

“…The presence of IDRs and LIPs in ZMIZ1 is consistent with its roles in the formation of multi-molecular complexes and transcriptional control, and potentially in the formation of super-enhancers. Recently, Zmiz1 has been identified as a super-enhancer associated gene, important for regulation of super-enhancer activity in response to estrogen during uterine development (58). Investigating the specific sequence determinants of these regions in the ZMIZ1 protein and their functional impact could offer valuable insights into the mechanisms governing Zmiz1-mediated signaling and regulation.…”

Dissection of cellular disruptions in autism spectrum disorder comorbidities

“…Although these genes have no known role in corticogenesis, their known functions in other systems guided our hypotheses. HNRNPC, for instance, has a potential connection to post-synaptic genes in ASD and alternative splicing (Wei et al, 2021), whereas CXXC4 is known to regulate Wnt signalling and Tet2, potentially playing a vital role in cell survival and maturation (Byun et al, 2020). GNAL has been suggested to contribute to neurodevelopmental disorder aetiology through neurotransmission regulation (Myhre et al, 2021), while C1QTNF4 is involved in immune pathways and may be linked to the autoimmune responses observed in ASD (Sarver et al, 2021).…”