Transcriptomic Analysis of the Neurogenesis Signature suggests Continued but Minimal Neurogenesis in the Adult Human Hippocampus

Abstract

PurposeSince immunohistological investigations have given rise to divergent perspectives about continued hippocampal neurogenesis in adult humans, a comprehensive transcriptomic analysis of the neurogenesis signature markers supplemented with insights from gliogenesis and apoptotic markers (in context to the developmental stages across age) may discern important aspects and may well be the appropriate methodology for resolving this conflict.\n\nMaterials and MethodsRNA expression data for the salient neurogenesis, gliogenesis, and apoptotic marker genes in post-mortem human hippocampal tissue of the Prenatal (n=15), Infant/Early childhood (n= 5), Adolescence (n=4), and Adulthood (n=6) ages were downloaded from Allen Brain Atlas database (http://www.brainspan.org/rnaseq). Gene expression data was categorized, median values were computed, and age group specific differential expression was statistically analyzed (the confidence level of 95%, p value [≤] 0.05 is used).\n\nResultsA sharp fall in prenatal to infant/early childhood expression was observed for all studied neurogenesis markers, except that for the post-mitotic late maturation (CALB1, CALB2, MAP2, NEUN, STMN2) which showed no significant differences in expression profiles. A continued post childhood decrease across advancing age was observed in the neural stem cells and progenitor markers with insignificant differences across close age groups. Uniquely, the postnatal sharp fall of KI67 and TBR2 continued across advancing age groups, reached near baseline until adolescent age. The immature granule cell, post mitotic early maturation, and late maturation markers showed a maintained or slightly increased (albeit insignificant) post childhood expression. The gliogenesis markers mostly showed a significant downregulation between prenatal and infant /early childhood age groups; this decline was persistent thereafter with insignificant differences between close age groups. A continued postnatal decrease occurred in apoptotic markers with observable, but insignificant, differences between adolescent and adult age.\n\nConclusionsOur findings indicate a possibility of continued but minimal neurogenesis in the adult human hippocampus. A significant part of the newborn cells in the neurogenic niche may be glial cells.\n\n(Findings of this study were first presented at the Annual Meeting of Society for Neuroscience (SFN), 3rd-7th November, 2018, San Diego, USA. https://abstractsonline.com/pp8/#!/4649/presentation/37213)\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC=\"FIGDIR/small/664995v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@3268f3org.highwire.dtl.DTLVardef@18855bborg.highwire.dtl.DTLVardef@1b46bdaorg.highwire.dtl.DTLVardef@14b929_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract\n\nC_FIG HighlightsO_LIA varying but continued fall in expression was observed for all studied neurogenesis markers across advancing age groups, except that for the immature granule cells, early and post-mitotic late neuronal maturation markers.\nC_LIO_LIA continued postnatal sharp fall of progenitor markers KI67 and TBR2 reached near baseline until adolescent age.\nC_LIO_LIGliogenesis markers showed continued but insignificant fall in expression post infant/early childhood.\nC_LIO_LIApoptotic markers showed continued post infant/early childhood downfall but changes were negligible between adolescent and adult age.\nC_LI