Unveiling glial pathways involved in neuronal communication DOI

Carlos Mallén Rivera

Published: Dec. 1, 2022

[EMBARGOED UNTIL 12/1/2023] Glia have been understudied throughout time largely because of a lack basic understanding. Early experiments showing that glia do not respond with action potentials after an electrical stimulation, like their neuronal counterparts did, greatly reduced the scope for studying glia. Now, we understand enough to know they neurons and can influence firing patterns. There is lot controversy in details behind how activity, some groups evidence glio-transmission, while other against glio-transmission. The major discrepancies between these two hypotheses come from use improper controls. A stronger comprehension glio-biology should reduce our ignorance allow us better address questions. Neither group denies glia's ability modulate so there still exists niche greater genetic understanding communicate neurons. Drosophila model organism excellent gaining insight onto glio-biology. overall goal this dissertation was identify glial genes which modify activity. To accomplish this, I took advantage TRPA1-induced paralysis behavior prowess forward modifier screens Then conducted secondary subsets utilized candidate identified first screen. Chapter 1 lays out general background information built on my research. In chapter 2, delve into specific modifiers using find utilize transporters calcium- SNARE-dependent mechanism alter We rationalized despite artificial activation through ectopic TRPA1 expression, data provide supporting 3, complexities observed including gender differences broad category tested. found strong male female flies particularly when were SNARE- or ion-related, unique biphasic temperature-dependent response behavior. addition, gap junction modulation From screen, ensheathing subset driver NP6520-GAL4 phenocopied results primary screen Repo-GAL4, concluding forms tripartite synapses glutamate-inhibitory neuron synapse. Lastly, 4 finishes up conclusions sets be tested future. Overall, further studies are needed fully elucidate interactions

Language: Английский

Gamma-aminobutyric acid (GABA): a comprehensive review of dietary sources, enrichment technologies, processing effects, health benefits, and its applications DOI
Dianzhi Hou, Jian Tang,

Qiqian Feng

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2023, Volume and Issue: 64(24), P. 8852 - 8874

Published: April 25, 2023

Gamma-aminobutyric acid (GABA) is a naturally occurring potential bioactive compound present in plants, microorganisms, animals, and humans. Especially, as main inhibitory neurotransmitter the central nervous system, GABA possesses broad spectrum of promising bioactivities. Thus, functional foods enriched with have been widely sought after by consumers. However, levels natural are usually low, which cannot meet people's demand for health effects. With increasing public awareness on food securities processes, using enrichment technologies to elevate contents instead exogenous addition can enhance acceptability health-conscious Herein, this review provides comprehensive insight dietary sources, technologies, processing effects GABA, its applications industry. Furthermore, various benefits GABA-enriched foods, mainly including neuroprotection, anti-insomnia, anti-depression, anti-hypertensive, anti-diabetes, anti-inflammatory also summarized. The challenges future research related exploring high producing strains, enhancing stability during storage, developing emerging without affecting quality other active ingredients. A better understanding may introduce new windows application foods.

Language: Английский

Citations

63
Ecdysone acts through cortex glia to regulate sleep in Drosophila DOI Creative Commons
Yongjun Li, Paula Haynes, Shirley Zhang

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 31, 2023

Steroid hormones are attractive candidates for transmitting long-range signals to affect behavior. These lipid-soluble molecules derived from dietary cholesterol easily penetrate the brain and act through nuclear hormone receptors (NHRs) that function as transcription factors. To determine extent which NHRs sleep:wake cycles, we knocked down each of 18 highly conserved found in Drosophila adults report ecdysone receptor (EcR) its direct downstream NHR Eip75B (E75) glia regulate rhythm amount sleep. Given synthesis genes have little no expression fly brain, appears a long-distance signal our data suggest it enters more at night. Anti-EcR staining localizes cortex functional screening glial subtypes revealed EcR functions adult Cortex implicated lipid metabolism, be relevant actions treatment mobilizes droplets (LDs), knockdown results LDs. In addition, sleep-promoting effects exogenous diminished lsd-2 mutant flies, lean deficient accumulation. We propose is systemic secreted factor modulates sleep by stimulating metabolism glia.

Language: Английский

Citations

24
Contributions of Gamma-Aminobutyric Acid (GABA) Produced by Lactic Acid Bacteria on Food Quality and Human Health: Current Applications and Future Prospects DOI Creative Commons
Mehmet Arif İçer,

Buse Sarikaya,

Emine Koçyiğit

et al.

Foods, Journal Year: 2024, Volume and Issue: 13(15), P. 2437 - 2437

Published: Aug. 1, 2024

The need to increase food safety and improve human health has led a worldwide in interest gamma-aminobutyric acid (GABA), produced by lactic bacteria (LABs). GABA, from glutamic reaction catalyzed glutamate decarboxylase (GAD), is four-carbon, non-protein amino that increasingly used the industry safety/quality of foods. In addition possible positive effects called postbiotic, on neuroprotection, improving sleep quality, alleviating depression relieving pain, various benefits GABA-enriched foods such as antidiabetic, antihypertension, anti-inflammatory are also being investigated. For all these reasons, it not surprising efforts identify LAB strains with high GABA productivity production LABs through genetic engineering yield accelerating. However, GABA's contributions have yet been fully discussed literature. Therefore, this current review highlights synthesis applications LABs, discusses its as, for example, drug withdrawal syndromes regulating obesity overeating. Still, other potential interactions (among others) remain unanswered questions be elucidated future. Hence, paves way toward further studies.

Language: Английский

Citations

13
Multicore fiber optic imaging reveals that astrocyte calcium activity in the mouse cerebral cortex is modulated by internal motivational state DOI Creative Commons

Yung‐Tian A. Gau,

Eric T. Hsu, Jaepyeong Cha

et al.

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

Published: April 8, 2024

Astrocytes are a direct target of neuromodulators and can influence neuronal activity on broad spatial temporal scales in response to rise cytosolic calcium. However, our knowledge about how astrocytes recruited during different animal behaviors remains limited. To measure astrocyte calcium vivo normative behaviors, we utilize high-resolution, long working distance multicore fiber optic imaging system that allows visualization individual transients the cerebral cortex freely moving mice. We define spatiotemporal dynamics changes diverse ranging from sleep-wake cycles exploration novel objects, showing their is more variable less synchronous than apparent head-immobilized conditions. In accordance with molecular diversity, often exhibit distinct thresholds patterns explorative allowing encoding across network. Astrocyte events were induced by noradrenergic cholinergic systems modulated internal state. The exhibited provides means vary neuromodulatory behavioral contexts states.

Language: Английский

Citations

8
Activation of GABA receptor attenuates intestinal inflammation by modulating enteric glial cells function through inhibiting NF-κB pathway DOI

Ziteng Deng,

Dan Li,

Xue Yan

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 329, P. 121984 - 121984

Published: July 30, 2023

Language: Английский

Citations

15
Glia: The Cellular Glue that binds Circadian Rhythms and Sleep DOI Creative Commons

Catarina Cavalhas-Almeida,

Amita Sehgal

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

Published: Jan. 15, 2025

Glia are increasingly appreciated as serving an important function in the control of sleep and circadian rhythms. Glial cells Drosophila mammals regulate daily rhythms locomotor activity well homeostatic rebound following deprivation. In addition, they contribute to proposed functions sleep, with different mapping varied glial subtypes. Here, we discuss recent findings rodent models establishing a role glia or regulation synaptic plasticity, brain metabolism, removal cellular debris immune challenges. These underscore relevance for benefits attributed have implications understanding neurobiological mechanisms underlying associated disorders.

Language: Английский

Citations

0
Role of astrocytes in sleep deprivation: accomplices, resisters, or bystanders? DOI Creative Commons

Mengxin Que,

Yujuan Li, Xuan Wang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 26, 2023

Sleep plays an essential role in all studied animals with a nervous system. However, sleep deprivation leads to various pathological changes and neurobehavioral problems. Astrocytes are the most abundant cells brain involved important functions, including neurotransmitter ion homeostasis, synaptic neuronal modulation, blood–brain barrier maintenance; furthermore, they associated numerous neurodegenerative diseases, pain, mood disorders. Moreover, astrocytes increasingly being recognized as vital contributors regulation of sleep-wake cycles, both locally specific neural circuits. In this review, we begin by describing regulating circadian rhythms, focusing on: (i) activity; (ii) metabolism; (iii) glymphatic system; (iv) neuroinflammation; (v) astrocyte–microglia cross-talk. review comorbidities deprivation-related Finally, discuss potential interventions targeting prevent or treat Pursuing these questions would pave way for deeper understanding cellular mechanisms underlying deprivation-comorbid

Language: Английский

Citations

9
Fly into tranquility: GABA’s role in Drosophila sleep DOI
Ratna Chaturvedi, Patrick Emery

Current Opinion in Insect Science, Journal Year: 2024, Volume and Issue: 64, P. 101219 - 101219

Published: June 5, 2024

Language: Английский

Citations

3
A transporter’s doom or destiny: SLC6A1 in health and disease, novel molecular targets and emerging therapeutic prospects DOI Creative Commons
Nikita Shah, Ameya Kasture, Florian P. Fischer

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 29, 2024

As the first member of solute carrier 6 (SLC6) protein family, γ-aminobutyric acid (GABA) transporter 1 (GAT1, SLC6A1 ), plays a pivotal role in uptake GABA from synaptic cleft into neurons and astrocytes. This process facilitates subsequent storage presynaptic vesicles. The human gene is highly susceptible to missense mutations, leading severe clinical outcomes, such as epilepsy, afflicted patients. molecular mechanisms -associated disorders are discerned some degree; many mutations now known impair folding, consequently fail reach plasma membrane. Inherently, once inside endoplasmic reticulum (ER), GAT1 abides by complex cascade events that enable efficient intracellular trafficking. involves association with specialized chaperones responsible for steering folding process, oligomerization, sorting through Golgi apparatus, ultimately delivery cell surface. entire subject stringent quality control at multiple checkpoints. While majority existing loss-of-function variants interfere membrane targeting, certain mutants retain abundant surface expression. In either scenario, suppressed activity disrupts GABAergic neurotransmission, preceding disease manifestation individuals harboring these mutations. nervous system enthralling calls systematic, groundbreaking research efforts dissect precise factors associated onset neurological disorders, uncover additional non-canonical therapeutic targets. Recent has given hope misfolded variants, which can be salvaged small molecules, i.e., chemical pharmacological chaperones, acting on upstream targets secretory pathway. We here highlight significance pharmacochaperoning strategy treatment -related disorders.

Language: Английский

Citations

3
Use-dependent, untapped dual kinase signaling localized in brain learning circuitry DOI
James C. Sears, Kendal Broadie

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1126232024 - e1126232024

Published: Jan. 24, 2024

Imaging brain learning and memory circuit kinase signaling is a monumental challenge. The s eparation of p hases-based ctivity r eporter k inase (SPARK) biosensors allow circuit-localized studies multiple interactive kinases in vivo , including protein A (PKA) extracellular signal-regulated (ERK) signaling. In the precisely-mapped Drosophila learning/memory circuit, we find PKA ERK differentially enriched distinct Kenyon cell connectivity nodes. We discover that potentiating normal activity induces signaling, expanding function within new presynaptic postsynaptic domains. Activity-induced shows extensive overlap with previously selective nodes, while activity-induced arises targeted synaptic transmission blockade cells elevates induction normally high baseline suggesting lateral feedback inhibition. overexpression pathway-linking Meng-Po (human SBK1) serine/threonine to improve acquisition consolidation results dramatically heightened separable revealing both synchronized untapped potential. Finally, mechanically-induced epileptic seizure model ( easily shocked “bang-sensitive” mutants) has strongly elevated, Both sexes were used all experiments, except for hemizygous male-only model. Hyperexcitable, learning-enhanced, models have comparably elevated common basis use-dependent induction. conclude modulation locally coordinated spatial dynamics underlying susceptibility linked Significance Statement Critical act circuits enable experience-dependent plasticity. This work images elucidate circuit-level organization relative mapped different exhibit domains, which reorganized by levels. newest kinase, Meng-Po/SBK1, co-regulates Targeted over-expression Meng-Po/SBK1 improves memory, indicating potential may enhance capabilities learn remember. Linked similarly increases circuitry, trade-off benefit instability. mechanistically connects hyperexcitation via

Language: Английский

Citations

2