PT  - JOURNAL ARTICLE
AU  - Ashutosh Kumar
AU  - Vikas Pareek
AU  - Muneeb A. Faiq
AU  - Pavan Kumar
AU  - Chiman Kumari
AU  - Himanshu N. Singh
AU  - Sanjib K. Ghosh
TI  - Transcriptomic Analysis of the Neurogenesis Signature suggests Continued but Minimal Neurogenesis in the Adult Human Hippocampus
AID  - 10.1101/664995
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 664995
4099  - http://biorxiv.org/content/early/2019/06/10/664995.short
4100  - http://biorxiv.org/content/early/2019/06/10/664995.full
AB  - Purpose Since 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.Materials and Methods RNA 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).Results A 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.Conclusions Our 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.(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)Graphical AbstractHighlightsA 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.A continued postnatal sharp fall of progenitor markers KI67 and TBR2 reached near baseline until adolescent age.Gliogenesis markers showed continued but insignificant fall in expression post infant/early childhood.Apoptotic markers showed continued post infant/early childhood downfall but changes were negligible between adolescent and adult age.