Symposium
Session Room 213
Session Room 213
Tuesday, June 17, 02:40 PM – 03:55 PM
Symposium 11: Adult neurogenesis or de-differentiation regulate hippocampus plasticity in health and disease
The existence and clinical relevance of human adult hippocampal neurogenesis (AHN) has been debated for decades (Boldrini et al., 2018). Hippocampal adult neurogenesis has been hypothesized to be involved in cognitive, emotional, and behavioral functions. New genomic studies continue to offer controversial findings. New findings suggest that the hippocampus dentate gyrus is able to de-differentiate (Hagihara et al., 2019). This adds a new level of complexity to its plasticity potential. Some studies reported that neural progenitor cells, neuroblasts, and immature neurons were detected in the hippocampus of elderly humans, based on the expressions of putative markers for these cells, suggesting that this proofs the persistence of AHN in humans.
Prof. Tsuyoshi Miyakawa will report on the phenomenon called dematuration, in which mature neurons dedifferentiate and re-express molecular markers of neural progenitor cells or immature neurons. He suggests that conditions that can induce dematuration, include inflammation and hyper-excitation of neurons. In this view, detection of immature cell markers may represent either AHN or dematuration.
Prof. Nora Abrous will discuss work investigating if stimulation of AHN is a sufficient condition to improve memory performance. Her team demonstrated that, in rats, this activation can improve accuracy and strength of memories, suggesting that stimulation of adult-born neuron activity can counteract the fading of memory traces that occurs with time. She also proposes hippocampal neurogenesis as the process underlying the evolutionary Baldwin effect (Abrous, Koehl and Lemoine, 2022), by which an organism's ability to learn and adapt learning new behaviors, e.g. with positive responses to stressors, will affect its reproductive success and will therefore influence the genetic makeup of the future generations. AHN would contribute to an organism's ontogenetic adaptation to a changing environment with a repertoire of cognitive and emotional behaviors. This theoretical framework posits that there would be a developmental vulnerability (or resilience), stemming from dysfunctional (or highly functional) developmental hippocampal neurogenesis, and an adult vulnerability (or resilience), stemming from dysfunctional (or highly functional) AHN. According to this hypothesis, developmental and adult vulnerability are distinct risk factors for different brain disorders in adults.
Prof. Maura Boldrini will show unpublished results of single nucleus multiomics (RAN and ATAC sequencing) and spatial transcriptomic of human postmortem hippocampus from neurotypical subjects and people with major Depressive Disorder (MDD), applied to investigate both the existence of a neurogenic niche in human, and if it is disrupted in MDD. Previous studies, including her work, showed smaller hippocampus dentate gyrus, fewer granule neurons and neural progenitors in MDD compared to neurotypical controls, but the molecular underpinnings of these changes remain unknown. Her team used machine learning, RNA Velocity and pseudotime trajectory inference and showed the presence of progenitor cells and their progeny and provided their anatomical mapping using spatial transcriptomics. MDD showed dysregulated genes in mature and immature granule neurons, excitatory and inhibitory neurons, ependyma, and microglia, suggesting altered AHN in MDD, together with increased inflammation and apoptosis, and altered synaptic function.
Their work suggests new avenues for research on AHN and its implications in cognition, emotions and behavior.
Prof. Tsuyoshi Miyakawa will report on the phenomenon called dematuration, in which mature neurons dedifferentiate and re-express molecular markers of neural progenitor cells or immature neurons. He suggests that conditions that can induce dematuration, include inflammation and hyper-excitation of neurons. In this view, detection of immature cell markers may represent either AHN or dematuration.
Prof. Nora Abrous will discuss work investigating if stimulation of AHN is a sufficient condition to improve memory performance. Her team demonstrated that, in rats, this activation can improve accuracy and strength of memories, suggesting that stimulation of adult-born neuron activity can counteract the fading of memory traces that occurs with time. She also proposes hippocampal neurogenesis as the process underlying the evolutionary Baldwin effect (Abrous, Koehl and Lemoine, 2022), by which an organism's ability to learn and adapt learning new behaviors, e.g. with positive responses to stressors, will affect its reproductive success and will therefore influence the genetic makeup of the future generations. AHN would contribute to an organism's ontogenetic adaptation to a changing environment with a repertoire of cognitive and emotional behaviors. This theoretical framework posits that there would be a developmental vulnerability (or resilience), stemming from dysfunctional (or highly functional) developmental hippocampal neurogenesis, and an adult vulnerability (or resilience), stemming from dysfunctional (or highly functional) AHN. According to this hypothesis, developmental and adult vulnerability are distinct risk factors for different brain disorders in adults.
Prof. Maura Boldrini will show unpublished results of single nucleus multiomics (RAN and ATAC sequencing) and spatial transcriptomic of human postmortem hippocampus from neurotypical subjects and people with major Depressive Disorder (MDD), applied to investigate both the existence of a neurogenic niche in human, and if it is disrupted in MDD. Previous studies, including her work, showed smaller hippocampus dentate gyrus, fewer granule neurons and neural progenitors in MDD compared to neurotypical controls, but the molecular underpinnings of these changes remain unknown. Her team used machine learning, RNA Velocity and pseudotime trajectory inference and showed the presence of progenitor cells and their progeny and provided their anatomical mapping using spatial transcriptomics. MDD showed dysregulated genes in mature and immature granule neurons, excitatory and inhibitory neurons, ependyma, and microglia, suggesting altered AHN in MDD, together with increased inflammation and apoptosis, and altered synaptic function.
Their work suggests new avenues for research on AHN and its implications in cognition, emotions and behavior.