The role of transcriptional and epigenetic modifications in astrogliogenesis DOI Creative Commons
Shuangping Ma, Lei Wang, Junhe Zhang

et al.

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e18151 - e18151

Published: Sept. 20, 2024

Astrocytes are widely distributed and play a critical role in the central nervous system (CNS) of human brain. During development CNS, astrocytes provide essential nutritional supportive functions for neural cells involved their metabolism pathological processes. Despite numerous studies that have reported on regulation astrogliogenesis at transcriptional epigenetic levels, there is paucity literature provides comprehensive summary key factors influencing this process. In review, we analyzed impact transcription ( e.g. , NFI, JAK/STAT, BMP, Ngn2), DNA methylation, histone acetylation, noncoding RNA astrocyte behavior astrogliogenesis, hope it enhances our comprehension mechanisms underlying offers theoretical foundation treatment patients with neurological diseases.

Language: Английский

Disease-associated astrocyte epigenetic memory promotes CNS pathology DOI
Hong‐Gyun Lee, Joseph M. Rone, Zhaorong Li

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8005), P. 865 - 872

Published: March 20, 2024

Language: Английский

Citations

34
Crym-positive striatal astrocytes gate perseverative behaviour DOI Creative Commons

Matthias Ollivier,

Joselyn S. Soto, Kay E. Linker

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8003), P. 358 - 366

Published: Feb. 28, 2024

Abstract Astrocytes are heterogeneous glial cells of the central nervous system 1–3 . However, physiological relevance astrocyte diversity for neural circuits and behaviour remains unclear. Here we show that a specific population astrocytes in striatum expresses μ-crystallin (encoded by Crym mice CRYM humans) is associated with several human diseases, including neuropsychiatric disorders 4–7 In adult mice, reducing levels striatal through CRISPR–Cas9-mediated knockout resulted perseverative behaviours, increased fast synaptic excitation medium spiny neurons dysfunctional excitatory–inhibitory balance. Increased perseveration stemmed from loss astrocyte-gated control neurotransmitter release presynaptic terminals orbitofrontal cortex–striatum projections. We found could be remedied using inhibitory chemogenetics 8 , this treatment also corrected deficits. Together, our findings reveal converging molecular, synaptic, circuit behavioural mechanisms which molecularly defined allocated gates phenotypes accompany 9–12 Our data -positive have key biological functions within system, uncover astrocyte–neuron interaction targeted treatments perseveration.

Language: Английский

Citations

19
Learning-associated astrocyte ensembles regulate memory recall DOI
Michael R. Williamson, Wookbong Kwon, Junsung Woo

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Language: Английский

Citations

18
Bidirectional histone monoaminylation dynamics regulate neural rhythmicity DOI Creative Commons
Qingfei Zheng, Benjamin H. Weekley,

David A. Vinson

et al.

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

Published: Jan. 8, 2025

Abstract Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles permissive gene expression 1–3 . We previously demonstrated serotonylation 4–10 and dopaminylation 9,11–13 histone (H3Q5ser H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), alter both local global chromatin states. Here we found TG2 additionally functions as eraser exchanger monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic contributes to circadian behaviour. H3Q5his, contrast H3Q5ser, inhibits the binding WDR5, a core member Lys4 (H3K4) methyltransferase complexes, thereby antagonizing activities on H3K4. Taken together, these data elucidate mechanism through single regulatory enzyme has ability sense chemical microenvironments affect states cells, dynamics regulation neural rhythmicity.

Language: Английский

Citations

4
Histone serotonylation in dorsal raphe nucleus contributes to stress- and antidepressant-mediated gene expression and behavior DOI Creative Commons
Amni Al-Kachak, G. Salvo, Sasha L. Fulton

et al.

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

Published: June 13, 2024

Mood disorders are an enigmatic class of debilitating illnesses that affect millions individuals worldwide. While chronic stress clearly increases incidence levels mood disorders, including major depressive disorder (MDD), stress-mediated disruptions in brain function precipitate these remain largely elusive. Serotonin-associated antidepressants (ADs) the first line therapy for many with symptoms, yet low remission rates and delays between treatment symptomatic alleviation have prompted skepticism regarding direct roles serotonin precipitation affective disorders. Our group recently demonstrated epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness brain. However, this non-canonical phenomenon has not been explored following and/or AD exposures. Here, we employed a combination genome-wide biochemical analyses dorsal raphe nucleus (DRN) male female mice exposed social defeat stress, as well DRN human MDD patients, examine impact exposures/MDD diagnosis on H3K4me3Q5ser dynamics, associations mark depression-related gene expression. We additionally assessed stress-induced/MDD-associated regulation exposures, viral-mediated reduce its stress-associated expression behavior. found plays important plasticity. Chronically stressed displayed dysregulated dynamics DRN, both AD- disruption proving sufficient attenuate Corresponding patterns were observed subjects vs. off ADs at their time death. These findings thus establish neurotransmission-independent role stress-/AD-associated behavioral plasticity, observations which may be clinical relevance treatment.

Language: Английский

Citations

13
Serotonin Transporter-dependent Histone Serotonylation in Placenta Contributes to the Neurodevelopmental Transcriptome DOI Creative Commons
Jennifer C Chan, Natália Alenina, Ashley M. Cunningham

et al.

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(7), P. 168454 - 168454

Published: Jan. 23, 2024

Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, placenta is thought to be an important contributor offspring brain 5-HT and critical overall fetal health. Yet, how placental acquired, mechanisms through which influences functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in can added histone proteins regulate transcription, process called H3 serotonylation. Here, we show that serotonylation undergoes dynamic during development, corresponding gene expression changes known influence key metabolic processes. Using transgenic mice, demonstrate dependent on uptake by transporter (SERT/SLC6A4). SERT deletion robustly reduces enrichment genome, disrupts neurodevelopmental networks early embryonic tissues. Thus, these findings suggest coordinating transcription at intersection maternal physiology development.

Language: Английский

Citations

11
Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders DOI Creative Commons
Takeshi Kondo,

Yuka Okada,

Shizuya Saika

et al.

European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(2), P. 151418 - 151418

Published: May 8, 2024

The nervous and immune systems are highly developed, each performs specialized physiological functions. However, they work together, their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, more general metabolites, essential for the appropriate regulation of both systems. Tryptophan, an amino acid, converted into functional molecules serotonin kynurenine, which play important roles in role kynurenine metabolites neurodegenerative psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity pathway a critical risk factor septic shock. In this review, first outline neuroimmune interactions tryptophan derivatives then summarized changes metabolism neurological disorders. Finally, discuss potential therapeutic targets

Language: Английский

Citations

9
Wiring and Volume Transmission: An Overview of the Dual Modality for Serotonin Neurotransmission DOI Creative Commons

Giulia Gianni,

Massimo Pasqualetti

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(23), P. 4093 - 4104

Published: Nov. 15, 2023

Serotonin is a neurotransmitter involved in the modulation of multitude physiological and behavioral processes. In spite relatively reduced number serotonin-producing neurons present mammalian CNS, complex long-range projection system provides profuse innervation to whole brain. Heterogeneity serotonin receptors, grouped seven families, their spatiotemporal expression pattern account for its widespread impact. Although neuronal communication occurs primarily at tiny gaps called synapses, wiring transmission, another mechanism based on extrasynaptic diffusion neuroactive molecules referred as volume has been described. While transmission rapid specific one-to-one modality communication, broader slower mode which single element can simultaneously act several different targets one-to-many mode. Some experimental evidence regarding ultrastructural features, localization receptors transporters, serotonin-glia interactions collected over past four decades supports existence serotonergic dual neurotransmission, coexist. To date, radical difference two modalities, limited information available way they are coordinated mediate activities participates. Understanding how modalities contribute neurotransmission utmost relevance comprehension functions both pathological conditions.

Language: Английский

Citations

19
Histone serotonylation regulates ependymoma tumorigenesis DOI
Hsiao‐Chi Chen, Peihao He, Malcolm F. McDonald

et al.

Nature, Journal Year: 2024, Volume and Issue: 632(8026), P. 903 - 910

Published: July 31, 2024

Language: Английский

Citations

6
Neuron–Glial Interactions: Implications for Plasticity, Behavior, and Cognition DOI
Mauricio Rangel‐Gomez, Cristina M. Alberini,

Benjamin Deneen

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(40), P. e1231242024 - e1231242024

Published: Oct. 2, 2024

The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, include a diversity other functions, such regulation complex behaviors. Astrocytes, the most abundant central nervous system (CNS), have been shown modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling behavioral functions. Contemporary studies further highlight astrocytes’ involvement cognitive For instance, inhibiting astrocytes hippocampus can lead memory deficits, suggesting their integral role processes. Moreover, astrocytic calcium activity astrocyte–neuron metabolic coupling linked changes strength learning. Microglia, another type cell, also extend beyond roles, contributing learning processes, with microglial reductions impacting these developmentally dependent manner. Oligodendrocytes, traditionally thought limited roles postdevelopment, are now recognized for activity-dependent modulation myelination plasticity, thus responses. Recent advancements computational modeling expanded our understanding particularly how influence circuits This review underscores importance CNS need research unravel complexities neuron–glia interactions, impact interactions on brain potential implications neurological diseases.

Language: Английский

Citations

5