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Browsing by Subject "Adult neurogenesis"
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Item Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways(Nature Research, 2019-10-10) Horgusluoglu-Moloch, Emrin; Risacher, Shannon L.; Crane, Paul K.; Hibar, Derrek; Thompson, Paul M.; Saykin, Andrew J.; Nho, Kwangsik; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Medical and Molecular Genetics, School of MedicineAdult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer's Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.Item In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury(Cell Press, 2021) Tai, Wenjiao; Wu, Wei; Wang, Lei-Lei; Ni, Haoqi; Chen, Chunhai; Yang, Jianjing; Zang, Tong; Zou, Yuhua; Xu, Xiao-Ming; Zhang, Chun-Li; Neurological Surgery, School of MedicineAdult neurogenesis plays critical roles in maintaining brain homeostasis and responding to neurogenic insults. However, the adult mammalian spinal cord lacks an intrinsic capacity for neurogenesis. Here we show that spinal cord injury (SCI) unveils a latent neurogenic potential of NG2+ glial cells, which can be exploited to produce new neurons and promote functional recovery after SCI. Although endogenous SOX2 is required for SCI-induced transient reprogramming, ectopic SOX2 expression is necessary and sufficient to unleash the full neurogenic potential of NG2 glia. Ectopic SOX2-induced neurogenesis proceeds through an expandable ASCL1+ progenitor stage and generates excitatory and inhibitory propriospinal neurons, which make synaptic connections with ascending and descending spinal pathways. Importantly, SOX2-mediated reprogramming of NG2 glia reduces glial scarring and promotes functional recovery after SCI. These results reveal a latent neurogenic potential of somatic glial cells, which can be leveraged for regenerative medicine.Item Regeneration Through in vivo Cell Fate Reprogramming for Neural Repair(Frontiers Media, 2020-04-24) Tai, Wenjiao; Xu, Xiao-Ming; Zhang, Chun-Li; Neurological Surgery, School of MedicineThe adult mammalian central nervous system (CNS) has very limited regenerative capacity upon neural injuries or under degenerative conditions. In recent years, however, significant progress has been made on in vivo cell fate reprogramming for neural regeneration. Resident glial cells can be reprogrammed into neuronal progenitors and mature neurons in the CNS of adult mammals. In this review article, we briefly summarize the current knowledge on innate adult neurogenesis under pathological conditions and then focus on induced neurogenesis through cell fate reprogramming. We discuss how the reprogramming process can be regulated and raise critical issues requiring careful considerations to move the field forward. With emerging evidence, we envision that fate reprogramming-based regenerative medicine will have a great potential for treating neurological conditions such as brain injury, spinal cord injury (SCI), Alzheimer's disease (AD), Parkinson's disease (PD), and retinopathy.Item Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus(Oxford University Press, 2018-06-01) Adamson, Sherleen Xue-Fu; Shen, Xubo; Jiang, Wendy; Lai, Vivien; Wang, Xiaoting; Cannon, Jason R.; Chen, Jinhui; Zheng, Wei; Shannahan, Jonathan H.; Neurological Surgery, School of MedicineAdult neurogenesis takes place in the brain subventricular zone (SVZ) in the lateral walls of lateral ventricles and subgranular zone (SGZ) in the hippocampal dentate gyrus (HDG), and functions to supply newborn neurons for normal brain functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in the SVZ. This study was designed to determine whether Mn exposure disturbed neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single dose of bromodeoxyuridine (BrdU) at the end of 4-week Mn exposure to label the proliferating cells. Immunostaining and cell counting data showed that BrdU(+) cells in Mn-exposed HDG were about 37% lower than that in the control (p < .05). The majority of BrdU(+) cells were identified as Sox2(+) cells. Another set of adult rats received BrdU injections for 3 consecutive days followed by 2- or 4-week Mn exposure to trace the fate of BrdU-labeled cells in the HDG. The time course studies indicated that Mn exposure significantly reduced the survival rate (54% at 2 weeks and 33% at 4 weeks), as compared with that in the control (80% at 2 weeks and 51% at 4 weeks) (p < .01). A significant time-dependent migration of newborn cells from the SGZ toward the granule cell layer was also observed in both control and Mn-exposed HDG. Triple-stained neuroblasts and mature neurons further revealed that Mn exposure significantly inhibited the differentiation of immature neuroblasts into mature neurons in the HDG. Taken together, these observations suggest that subchronic Mn exposure results in a reduced cell proliferation, diminished survival of adult-born neurons, and inhibited overall neurogenesis in the adult HDG. Impaired adult neurogenesis is likely one of the mechanisms contribute to Mn-induced Parkinsonian disorder.