Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice DOI Creative Commons
Pascal Bielefeld, Araks Martirosyan, Soraya Martín‐Suárez

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 18, 2024

Abstract Traumatic brain injury (TBI) can result in long-lasting changes hippocampal function. The induced by TBI on the hippocampus contribute to cognitive deficits. adult harbors neural stem cells (NSCs) that generate neurons (neurogenesis), and astrocytes (astrogliogenesis). While deregulation of NSCs neurogenesis have been observed after TBI, it is not known how may affect astrogliogenesis. Using a controlled cortical impact model male mice, single cell RNA sequencing spatial transcriptomics, we assessed affected neuronal astroglial lineages derived from them. We observe an increase NSC-derived concomitant decrease astrocytic cells, together with gene expression dysplasia within dentate gyrus. Here, show modifies NSC fate promote at cost astrogliogenesis identify specific populations as possible targets counteract TBI-induced cellular hippocampus.

Language: Английский

Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis DOI Creative Commons
Stefanie Grabrucker, Moira Marizzoni, Edina Silajdžić

et al.

Brain, Journal Year: 2023, Volume and Issue: 146(12), P. 4916 - 4934

Published: Oct. 18, 2023

Alzheimer's disease is a complex neurodegenerative disorder leading to decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor by showing specific alterations microbiome composition of patients rodent models. However, it unknown whether are causal manifestation symptoms. To understand involvement patient host physiology behaviour, we transplanted faecal from age-matched healthy controls into microbiota-depleted young adult rats. We found impairments behaviours reliant on hippocampal neurogenesis, essential process for certain memory functions mood, resulting transplants. Notably, severity correlated with clinical scores donor patients. Discrete changes rat caecal metabolome were also evident. As neurogenesis cannot be measured living humans but modulated circulatory systemic environment, assessed impact environment proxy readouts. Serum decreased human cells vitro associated key microbial genera. Our findings reveal first time, that symptoms can transferred organism via microbiota, confirming role disease, highlight converging central cellular regulating gut-mediated factors Alzheimer's.

Language: Английский

Citations

122
Insights into Alzheimer’s disease from single-cell genomic approaches DOI
Mitchell H. Murdock, Li‐Huei Tsai

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(2), P. 181 - 195

Published: Jan. 2, 2023

Language: Английский

Citations

104
Adult hippocampal neurogenesis in Alzheimer’s disease: A roadmap to clinical relevance DOI Creative Commons
Evgenia Salta, Orly Lazarov, Carlos P. Fitzsimons

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(2), P. 120 - 136

Published: Feb. 1, 2023

Adult hippocampal neurogenesis (AHN) drops sharply during early stages of Alzheimer's disease (AD), via unknown mechanisms, and correlates with cognitive status in AD patients. Understanding AHN regulation could provide a framework for innovative pharmacological interventions. We here combine molecular, behavioral, clinical data critically discuss the multicellular complexity niche relation to pathophysiology. further present roadmap toward better understanding role by probing promises caveats latest technological advancements field addressing conceptual methodological challenges ahead.

Language: Английский

Citations

82
Automatic cell-type harmonization and integration across Human Cell Atlas datasets DOI Creative Commons
Chuan Xu, Martin Prete, Simone Webb

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(26), P. 5876 - 5891.e20

Published: Dec. 1, 2023

Harmonizing cell types across the single-cell community and assembling them into a common framework is central to building standardized Human Cell Atlas. Here, we present CellHint, predictive clustering tree-based tool resolve cell-type differences in annotation resolution technical biases datasets. CellHint accurately quantifies cell-cell transcriptomic similarities places relationship graph that hierarchically defines shared unique subtypes. Application multiple immune datasets recapitulates expert-curated annotations. also reveals underexplored relationships between healthy diseased lung states eight diseases. Furthermore, workflow for fast cross-dataset integration guided by harmonized hierarchy, which uncovers underappreciated adult human hippocampus. Finally, apply 12 tissues from 38 datasets, providing deeply curated cross-tissue database with ∼3.7 million cells various machine learning models automatic tissues.

Language: Английский

Citations

76
Genetics of human brain development DOI
Yi Zhou, Hongjun Song, Guo‐li Ming

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: Английский

Citations

74
Formation of memory assemblies through the DNA-sensing TLR9 pathway DOI Creative Commons
Vladimir Jovasevic, Elizabeth Wood, Ana Cicvaric

et al.

Nature, Journal Year: 2024, Volume and Issue: 628(8006), P. 145 - 153

Published: March 27, 2024

Abstract As hippocampal neurons respond to diverse types of information 1 , a subset assembles into microcircuits representing memory 2 . Those typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage 3–5 Here we found discrete clusters excitatory CA1 with persistent double-stranded (dsDNA) breaks, nuclear envelope ruptures and perinuclear release histone dsDNA fragments hours after learning. Following these early events, some acquired an inflammatory phenotype involving activation TLR9 signalling accumulation centrosomal repair complexes 6 Neuron-specific knockdown Tlr9 impaired while blunting contextual fear conditioning-induced changes gene expression specific neurons. Notably, had essential role centrosome function, including repair, ciliogenesis build-up perineuronal nets. We demonstrate novel cascade learning-induced events neuronal undergoing TLR9-mediated their recruitment circuits. With compromised this fundamental mechanism becomes gateway genomic instability cognitive impairments implicated accelerated senescence, psychiatric disorders neurodegenerative disorders. Maintaining the integrity thus emerges as promising preventive strategy for neurocognitive deficits.

Language: Английский

Citations

49
Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease DOI
Yadong Li, Yan‐Jia Luo,

Ling Xie

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(4), P. 415 - 432.e6

Published: April 1, 2023

Language: Английский

Citations

48
Mapping human adult hippocampal neurogenesis with single-cell transcriptomics: Reconciling controversy or fueling the debate? DOI Creative Commons
Giorgia Tosoni, Dilara Ayyildiz, Julien Bryois

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(11), P. 1714 - 1731.e3

Published: April 3, 2023

The notion of exploiting the regenerative potential human brain in physiological aging or neurological diseases represents a particularly attractive alternative to conventional strategies for enhancing restoring function. However, major first question address is whether does possess ability regenerate. existence adult hippocampal neurogenesis (AHN) has been at center fierce scientific debate many years. advent single-cell transcriptomic technologies was initially viewed as panacea resolving this controversy. recent RNA sequencing studies hippocampus yielded conflicting results. Here, we critically discuss and re-analyze previously published AHN-related datasets. We argue that, although promising, profiling AHN can be confounded by methodological, conceptual, biological factors that need consistently addressed across openly discussed within community.

Language: Английский

Citations

45
Neurobiology and systems biology of stress resilience DOI
Raffaël Kalisch, Scott J. Russo,

Marianne B. Müller

et al.

Physiological Reviews, Journal Year: 2024, Volume and Issue: 104(3), P. 1205 - 1263

Published: March 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Language: Английский

Citations

31
The concept of resilience to Alzheimer’s Disease: current definitions and cellular and molecular mechanisms DOI Creative Commons
Luuk E. de Vries,

Inge Huitinga,

Helmut W. Kessels

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 8, 2024

Abstract Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience evolved into a widely debated concept. External factors such stimulation associated with AD, but exact cellular molecular underpinnings not completely understood. In this review, we discuss current definitions used in field, highlight translational approaches investigate AD summarize underlying substrates that have derived from human animal studies, which received more attention last few years. From these studies picture emerges resilient different patients terms specific pathological species reaction pathology, possibly helps up certain tipping point. Studying rare can be great importance it could pave way novel therapeutic avenues for AD.

Language: Английский

Citations

26