NAD + metabolism drives astrocyte proinflammatory reprogramming in central nervous system autoimmunity DOI Creative Commons

Tom Meyer,

Dor Shimon,

Sawsan Youssef

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(35)

Опубликована: Авг. 22, 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Astrocytes are most abundant glial cells in CNS, and their dysfunction contributes to pathogenesis MS its animal model, experimental autoimmune encephalomyelitis (EAE). Recent advances highlight pivotal role cellular metabolism programming immune responses. However, underlying immunometabolic mechanisms that drive astrocyte pathogenicity remain elusive. Nicotinamide adenine dinucleotide (NAD + ) vital coenzyme involved redox reactions substrate for NAD -dependent enzymes. Cellular levels dynamically controlled by synthesis degradation, dysregulation this balance has been associated with inflammation disease. Here, we demonstrate cell-autonomous generation via salvage pathway regulates function. Inhibition nicotinamide phosphoribosyltransferase (NAMPT), key enzyme pathway, results depletion , inhibits oxidative phosphorylation, limits potential. We identified CD38 as main NADase up-regulated reactive mouse human astrocytes models neuroinflammation MS. Genetic or pharmacological blockade activity augmented levels, suppressed proinflammatory transcriptional reprogramming, impaired chemotactic potential monocytes, ameliorated EAE. found mediated calcineurin/NFAT signaling astrocytes. Thus, NAMPT–NAD –CD38 circuitry controls ability meet energy demands drives expression modules, contributing CNS pathology EAE and, potentially, Our identify candidate therapeutic targets

Язык: Английский

CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord DOI
Shuhui Sun, Jiaming Li, Si Wang

и другие.

Nature, Год журнала: 2023, Номер 624(7992), С. 611 - 620

Опубликована: Окт. 31, 2023

Язык: Английский

Процитировано

36

Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons DOI Creative Commons
Ee Shan Liau, Suoqin Jin, Yen‐Chung Chen

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 3, 2023

Abstract Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate movements. In vertebrates, the molecular identities of cardinal MN types such as those innervating limb versus trunk muscles are well elucidated. Yet finer subtypes within these cell populations that innervate individual muscle groups remain enigmatic. Here we investigate heterogeneity in mouse MNs using single-cell transcriptomics. Among limb-innervating MNs, reveal a diverse neuropeptide code for delineating putative pool identities. Additionally, uncover axial subdivided into three molecularly distinct subtypes, defined by mediolaterally-biased Satb2, Nr2f2 or Bcl11b expression patterns with different axon guidance signatures. These present chicken human embryos, suggesting conserved pattern across higher vertebrates. Overall, our study provides resource spinal paves way towards deciphering how neuronal evolved accommodate vertebrate behaviors.

Язык: Английский

Процитировано

35

Cerebrospinal fluid-contacting neurons: multimodal cells with diverse roles in the CNS DOI
Claire Wyart, Martin Carbó-Tano, Yasmine Cantaut-Belarif

и другие.

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(9), С. 540 - 556

Опубликована: Авг. 9, 2023

Язык: Английский

Процитировано

34

Single-cell transcriptomic landscape of the developing human spinal cord DOI
Jimena Andersen, Nicholas Thom, Jennifer L. Shadrach

и другие.

Nature Neuroscience, Год журнала: 2023, Номер 26(5), С. 902 - 914

Опубликована: Апрель 24, 2023

Язык: Английский

Процитировано

32

Determinants of motor neuron functional subtypes important for locomotor speed DOI Creative Commons
Kristen P. D’Elia, Hanna Hameedy, Dena Goldblatt

и другие.

Cell Reports, Год журнала: 2023, Номер 42(9), С. 113049 - 113049

Опубликована: Сен. 1, 2023

Locomotion requires precise control of the strength and speed muscle contraction is achieved by recruiting functionally distinct subtypes motor neurons (MNs). MNs are essential to movement differentially susceptible in disease, but little known about how acquire functional subtype-specific features during development. Using single-cell RNA profiling embryonic larval zebrafish, we identify novel conserved molecular signatures for MN genes expressed both early post-mitotic mature MNs. Assessing development genetic mutants, define a program subtype specification. Two evolutionarily transcription factors, Prdm16 Mecom, determinants integral fast Loss prdm16 or mecom causes develop transcriptional profiles innervation similar slow These results reveal diversity vertebrate axial demonstrate that specified through intrinsic codes.

Язык: Английский

Процитировано

30

Spinal Interneurons: Diversity and Connectivity in Motor Control DOI Creative Commons
Mohini Sengupta, Martha W. Bagnall

Annual Review of Neuroscience, Год журнала: 2023, Номер 46(1), С. 79 - 99

Опубликована: Фев. 28, 2023

The spinal cord is home to the intrinsic networks for locomotion. An animal in which has been fully severed from brain can still produce rhythmic, patterned locomotor movements as long some excitatory drive provided, such physical, pharmacological, or electrical stimuli. Yet it remains a challenge define underlying circuitry that produces these because contains wide variety of neuron classes whose patterns interconnectivity are poorly understood. Computational models locomotion accordingly rely on untested assumptions about network element identity and connectivity. In this review, we consider neurons, their interconnectivity, significance circuit connections along axis cord. We suggest several lines analysis move toward definitive understanding network.

Язык: Английский

Процитировано

26

Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia DOI Creative Commons
Shamsuddin A. Bhuiyan, Mengyi Xu,

Lite Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 5, 2023

Abstract Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli including touch, temperature, pain central nervous system. Recent advances single-cell RNA-sequencing (scRNA-seq) have provided new insights into diversity of ganglia cell types rodents, non-human primates, humans, but it remains difficult compare transcriptomically defined across studies species. Here, we built cross-species harmonized atlases DRG TG that describe 18 neuronal 11 non-neuronal 6 species 19 studies. We then demonstrate utility this reference atlas by using annotate newly profiled nuclei/cells from both human highly regenerative axolotl. observe transcriptomic profiles neuron subtypes broadly similar vertebrates, expression functionally important neuropeptides channels can vary notably. The resources data presented here guide future comparative transcriptomics, simplify type nomenclature differences studies, help prioritize targets for therapy development.

Язык: Английский

Процитировано

26

Molecular and spatial profiling of the paraventricular nucleus of the thalamus DOI Creative Commons
Claire Gao, Chiraag Gohel, Yan Leng

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 3, 2023

The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked cellular differences, molecular identity spatial distribution cell types remain unclear. To address this gap, here we used single RNA sequencing (snRNA-seq) identified five molecularly distinct neuronal subtypes in mouse brain. Additionally, multiplex fluorescent situ hybridization top marker genes revealed that are organized by a combination previously unidentified gradients. Lastly, comparing our dataset with recently published single-cell atlas yielded novel insight into PVT’s connectivity cortex, including unexpected innervation auditory visual areas. This comparison also data contains largely non-overlapping transcriptomic map multiple midline thalamic nuclei. Collectively, findings uncover unknown features anatomical organization provide valuable resource for future investigations.

Язык: Английский

Процитировано

24

A topographical atlas of α-synuclein dosage and cell type-specific expression in adult mouse brain and peripheral organs DOI Creative Commons
Haley Geertsma, Zoe Fisk,

Lillian Sauline

и другие.

npj Parkinson s Disease, Год журнала: 2024, Номер 10(1)

Опубликована: Март 19, 2024

Parkinson's disease (PD) is the second most common neurodegenerative worldwide and presents pathologically with Lewy pathology dopaminergic neurodegeneration. contains aggregated α-synuclein (αSyn), a protein encoded by SNCA gene which also mutated or duplicated in subset of familial PD cases. Due to its predominant presynaptic localization, immunostaining for results diffuse reactivity pattern, providing little insight into types cells expressing αSyn. As result, αSyn expression-driven cellular vulnerability has been difficult ascertain. Using combination knock-in mice that target nucleus (Snca

Язык: Английский

Процитировано

15

Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV+ interneurons DOI Creative Commons

Genelle Rankin,

Anda M. Chirila,

Alan J. Emanuel

и другие.

Cell Reports, Год журнала: 2024, Номер 43(2), С. 113718 - 113718

Опубликована: Янв. 30, 2024

How mechanical allodynia following nerve injury is encoded in patterns of neural activity the spinal cord dorsal horn (DH) remains incompletely understood. We address this mice using spared model neuropathic pain and vivo electrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to stimuli injury, an overall increase sensitivity or reactivity DH neurons not observed. do, however, observe a marked decrease correlated firing patterns, including synchrony stimulus-evoked firing, across DH. Alterations temporal are recapitulated by silencing parvalbumin+ (PV+) interneurons, previously implicated allodynia, as allodynic pain-like behaviors. These findings reveal decorrelated network activity, driven alterations PV+ prominent feature suggest restoration proper potential therapeutic strategy treat chronic pain.

Язык: Английский

Процитировано

10