Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain DOI Creative Commons

Cecilie Skarstad Norevik,

Aleksi M. Huuha,

Ragnhild N. Røsbjørgen

et al.

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2023, Volume and Issue: 13(2), P. 245 - 255

Published: July 25, 2023

Exercise training promotes brain plasticity and is associated with protection against cognitive impairment Alzheimer's disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate blood plasma from exercise-trained donors on neuronal viability, vivo rat test whether such impacts function, amyloid pathology, neurogenesis. Mouse hippocampal cells were exposed AD-like stress using amyloid-β treated collected human male 3 h after a single bout high-intensity exercise. For studies, was young Wistar rats (high-intensity intervals 5 days/week for 6 weeks). Transgenic (McGill-R-Thy1-APP) injected times/fortnight weeks at 2 months or age either (a) the rats, (b) sedentary (c) saline. Cognitive plaque neurogenesis assessed. The treatment analyzed 23 cytokines. Plasma exercised enhanced cell viability 44.1% (p = 0.032) reduced atrophy 50.0% < 0.001) amyloid-β-treated cells. In did not alter function pathology but increase ∼3-fold, regardless pathological stage, when compared saline-treated rats. Concentrations 7 cytokines significantly plasma. Our proof-of-concept study demonstrates that can protect culture promote adult brain. This effect due pro-inflammatory signaling molecules

Language: Английский

Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology DOI Creative Commons
Fernando Maestú, Willem de Haan, Marc Aurel Busche

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 69, P. 101372 - 101372

Published: May 21, 2021

Our incomplete understanding of the link between Alzheimer's Disease pathology and symptomatology is a crucial obstacle for therapeutic success. Recently, translational studies have begun to connect dots protein alterations deposition, brain network dysfunction cognitive deficits. Disturbance neuronal activity, in particular an imbalance underlying excitation/inhibition (E/I), appears early AD, can be regarded as forming central structural dysfunction. While there are emerging (non-)pharmacological options influence this imbalance, complexity human dynamics has hindered identification optimal approach. We suggest that focusing on integration neurophysiological aspects AD at micro-, meso- macroscale, with support computational modeling, unite fundamental clinical knowledge, provide general framework, rational targets.

Language: Английский

Citations

147
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

79
Single-cell transcriptomics of adult macaque hippocampus reveals neural precursor cell populations DOI
Zhao-Zhe Hao,

Jia-Ru Wei,

Dongchang Xiao

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(6), P. 805 - 817

Published: May 30, 2022

Language: Английский

Citations

73
Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells DOI Creative Commons
Francesco Petrelli, Valentina Scandella,

Sylvie Montessuit

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(9)

Published: March 1, 2023

Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation not fully understood. We here show that mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part this process. MPC transports into mitochondria, linking cytosolic glycolysis tricarboxylic acid cycle oxidative phosphorylation. Despite metabolic key function, of NSPCs has been addressed. quiescent have an active express high levels MPC. Pharmacological inhibition increases aspartate triggers NSPC activation. Furthermore, genetic Mpc1 ablation vitro vivo also activates NSPCs, which differentiate mature neurons, leading overall increased hippocampal neurogenesis aged mice. These findings highlight importance regulation identify pathway through import controls

Language: Английский

Citations

52
Brain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice DOI Creative Commons
Kelly Jin, Zizhen Yao, Cindy T. J. van Velthoven

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Biological ageing can be defined as a gradual loss of homeostasis across various aspects molecular and cellular function1,2. Mammalian brains consist thousands cell types3, which may differentially susceptible or resilient to ageing. Here we present comprehensive single-cell RNA sequencing dataset containing roughly 1.2 million high-quality transcriptomes brain cells from young adult aged mice both sexes, regions spanning the forebrain, midbrain hindbrain. High-resolution clustering all results in 847 clusters reveals at least 14 age-biased that are mostly glial types. At broader subclass supertype levels, find age-associated gene expression signatures provide list 2,449 unique expressed genes (age-DE genes) for many neuronal non-neuronal Whereas most age-DE specific types, observe common with including decrease related structure function neuron major astrocyte types mature oligodendrocytes, an increase immune function, antigen presentation, inflammation, motility some vascular Finally, demonstrate greatest sensitivity concentrated around third ventricle hypothalamus, tanycytes, ependymal cells, certain arcuate nucleus, dorsomedial nucleus paraventricular express canonically energy homeostasis. Many these response. These findings suggest hypothalamus hub mouse brain. Overall, this study systematically delineates dynamic landscape cell-type-specific transcriptomic changes associated normal will serve foundation investigation functional interaction disease. A inform into

Language: Английский

Citations

7
The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis DOI
Miguel Marin-Rodero, Elisa Cintado, Alec J. Walker

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on immunocytes guard homeostasis in healthy individuals remains limited. This study highlights heterogeneous, polyfunctional regulatory T cell (T reg ) compartment meninges. A subtype specialized controlling interferon-gamma (IFN-γ) responses another dedicated regulating follicular B were substantial components this compartment. Accordingly, punctual ablation rapidly unleashed IFN-γ production by lymphocytes, unlocked access parenchyma, altered profiles. Distally, hippocampus assumed a reactive state, with morphological transcriptional changes multiple glial types. Within dentate gyrus, neural stem underwent more death blocked from further differentiation, which coincided impairments short-term spatial-reference memory. Thus, regs multifaceted safeguard at steady state.

Language: Английский

Citations

3
Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus DOI Creative Commons
Yi‐Cheng Wu,

Vladyslav I. Korobeynyk,

Margherita Zamboni

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: 28(2), P. 415 - 430

Published: Jan. 6, 2025

Abstract The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, DG dysfunction has been implicated age-related diseases. Although neurogenic potential maintained throughout life the as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, implications for cognitive decline disease. In this study, we used single-cell RNA sequencing characterize transcriptomic signatures their surrounding niche, identifying molecular changes associated aging from activation quiescent NSCs maturation fate-committed progeny. By integrating spatial transcriptomics data, identified regional invasion inflammatory into hippocampus age show here that early-onset neuroinflammation activity. Our data reveal lifelong dynamics niche provide a powerful resource understand alterations hippocampus.

Language: Английский

Citations

2
Adult-born dentate granule cells promote hippocampal population sparsity DOI Creative Commons
Stephen B. McHugh, Vítor Lopes‐dos‐Santos, Giuseppe P. Gava

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(11), P. 1481 - 1491

Published: Oct. 10, 2022

Abstract The dentate gyrus (DG) gates neocortical information flow to the hippocampus. Intriguingly, DG also produces adult-born granule cells (abDGCs) throughout lifespan, but their contribution downstream firing dynamics remains unclear. Here, we show that abDGCs promote sparser hippocampal population spiking during mnemonic processing of novel stimuli. By combining triple-(DG-CA3-CA1) ensemble recordings and optogenetic interventions in behaving mice, constitute a subset high-firing-rate neurons with enhanced activity responses novelty strong modulation by theta oscillations. Selectively activating 4–7-week post-birth period increases sparsity patterns, whereas suppressing reduces this sparsity, principal cell rates impairs object recognition reduced dimensionality network structure, without affecting single-neuron spatial representations. We propose transiently support structure for higher-dimensional relevant effective processing.

Language: Английский

Citations

65
Exerkines and long-term synaptic potentiation: Mechanisms of exercise-induced neuroplasticity DOI Creative Commons
Wouter A.J. Vints, Oron Levin, Hakuei Fujiyama

et al.

Frontiers in Neuroendocrinology, Journal Year: 2022, Volume and Issue: 66, P. 100993 - 100993

Published: March 11, 2022

Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that facilitation of long-term synaptic potentiation (LTP)-related pathways, products induced physical (i.e., exerkines), is a crucial aspect exercise-effect on This review summarizes pathways are activated exerkines potentiate LTP. For total 16 exerkines, we indicated how blood brain exerkine levels altered depending type cardiovascular or resistance exercise) they respond to single bout acute multiple bouts chronic exercise). information be used for designing individualized programs. Finally, this serve direct future research towards fundamental gaps in our current knowledge regarding biophysical interactions between muscle activity at both system levels.

Language: Английский

Citations

64
Chronic in vivo imaging defines age-dependent alterations of neurogenesis in the mouse hippocampus DOI Creative Commons
Yi‐Cheng Wu, Sara Bottes,

Roberto Fisch

et al.

Nature Aging, Journal Year: 2023, Volume and Issue: 3(4), P. 380 - 390

Published: Feb. 20, 2023

Abstract Neural stem cells (NSCs) generate new neurons throughout life in the mammalian hippocampus 1 . Advancing age leads to a decline neurogenesis, which is associated with impaired cognition 2,3 The cellular mechanisms causing reduced neurogenesis advancing remain largely unknown. We genetically labeled NSCs through conditional recombination driven by regulatory elements of stem-cell-expressed gene GLI family zinc finger (Gli1) and used chronic intravital imaging follow individual their daughter over months within hippocampal niche 4,5 show that aging affects multiple steps, from cell cycle entry quiescent determination number surviving cells, ultimately clonal output NSCs. Thus, we here define developmental stages may be targeted enhance aim maintaining plasticity age.

Language: Английский

Citations

32