scholarly journals Purinergic signaling controls spontaneous activity in the auditory system throughout early development

2020 ◽  
Author(s):  
Travis A. Babola ◽  
Sally Li ◽  
Zhirong Wang ◽  
Calvin Kersbergen ◽  
Ana Belén Elgoyhen ◽  
...  
Keyword(s):  
Electrical Activity ◽  
Spontaneous Activity ◽  
Auditory System ◽  
Developmental Disorders ◽  
Developmental Stages ◽  
Purinergic Signaling ◽  
Atp Release ◽  
Auditory Neurons ◽  
Ganglion Neurons

ABSTRACTSpontaneous bursts of electrical activity in the developing auditory system arise within the cochlea prior to hearing onset and propagate through future sound processing circuits of the brain to promote maturation of auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K+ efflux and subsequent depolarization of inner hair cells (IHCs). However, little is known about when this activity emerges or whether different mechanisms underlie distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in IHCs and spiral ganglion neurons (SGNs), which begins at birth and follows a base to apex developmental gradient. At all developmental stages, pharmacological inhibition of P2Y1 metabotropic purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging within the inferior colliculus of awake mice revealed that auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period, yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea, indicate that this input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the auditory system uses a consistent mechanism involving ATP release from ISCs and activation of purinergic autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound.SIGNIFICANCE STATEMENTIn developing sensory systems, groups of neurons that will process information from similar sensory space exhibit highly correlated electrical activity that is critical for proper maturation and circuit refinement. Defining the period when this activity is present, the mechanisms responsible and the features of this activity are crucial for understanding how spontaneous activity influences circuit development. We show that, from birth to hearing onset, the auditory system relies on a consistent mechanism to elicit correlate firing of neurons that will process similar frequencies of sound. Targeted disruption of this activity will increase our understanding of how these early circuits mature and may provide insight into processes responsible for developmental disorders of the auditory system.

Spontaneous activity of cat spinal ganglion neurons in vivo

1993 ◽  
Vol 31 (5) ◽  
pp. 523-530 ◽  
Author(s):  
Lu Guo-Wei ◽  
Marvin J. Hoffert ◽  
Vjekoslav Miletic
Keyword(s):  
Spontaneous Activity ◽  
Spinal Ganglion ◽  
Spinal Ganglion Neurons ◽  
Ganglion Neurons

scholarly journals ATP-release drives inflammation with lysophosphatidylcholine

2020 ◽  
Author(s):  
Sana Ismaeel ◽  
Ayub Qadri
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Purinergic Signaling ◽  
Low Density Lipoprotein ◽  
Neuronal Cells ◽  
Atp Release ◽  
Density Lipoprotein ◽  
Independent Manner ◽  
Caspase 1

AbstractLysophosphatidylcholine (LPC), a dominant lipid component of oxidized low-density lipoprotein, plays a major role in inflammation associated with atherosclerosis and neurodegenerative disorders. It activates inflammatory responses from macrophages, neuronal cells and endothelial cells. However, the exact mechanism by which LPC promotes inflammation remains incompletely understood. Here, we show that the production of inflammatory cytokines and cytotoxicity with LPC are both critically dependent on its ability to bring about release of ATP from cells. The induction of caspase-1-mediated IL-1β-release with LPC from TLR-primed macrophages and neuronal cells is reduced in presence of ATP-hydrolyzing enzyme, apyrase and the inhibitors of purinergic signaling. ATP released from LPC-treated cells also promotes an IL-12p70hi, low phagocytic and poorly co-stimulatory phenotype in macrophages in a caspase-1 – independent manner. Treatment with apyrase reduces production of inflammatory cytokines with LPC in vivo. These findings reveal a previously unappreciated pathway for generation of inflammatory responses with LPC, and these have significant implications for therapeutic intervention in chronic inflammatory disorders promoted by this lipid.

scholarly journals Kölliker’s Organ and the Development of Spontaneous Activity in the Auditory System: Implications for Hearing Dysfunction

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
M. W. Nishani Dayaratne ◽  
Srdjan M. Vlajkovic ◽  
Janusz Lipski ◽  
Peter R. Thorne
Keyword(s):  
Spontaneous Activity ◽  
Auditory System ◽  
Purinergic Signalling ◽  
Auditory Neurons ◽  
Supporting Cells ◽  
Developmental Abnormalities ◽  
Neural Connections ◽  
P2 Purinergic Receptors ◽  
Auditory Development ◽  
Connexin Hemichannels

Prior to the “onset of hearing,” developing cochlear inner hair cells (IHCs) and primary auditory neurons undergo experience-independent activity, which is thought to be important in retaining and refining neural connections in the absence of sound. One of the major hypotheses regarding the origin of such activity involves a group of columnar epithelial supporting cells forming Kölliker’s organ, which is only present during this critical period of auditory development. There is strong evidence for a purinergic signalling mechanism underlying such activity. ATP released through connexin hemichannels may activate P2 purinergic receptors in both Kölliker’s organ and the adjacent IHCs, leading to generation of electrical activity throughout the auditory system. However, recent work has suggested an alternative origin, by demonstrating the ability of IHCs to generate this spontaneous activity without activation by ATP. Regardless, developmental abnormalities of Kölliker’s organ may lead to congenital hearing loss, considering that mutations in ion channels (hemichannels, gap junctions, and calcium channels) involved in Kölliker’s organ activity share strong links with such types of deafness.

scholarly journals Purinergic signaling controls spontaneous activity in the auditory system throughout early development

2020 ◽  
pp. JN-RM-2178-20
Author(s):  
Travis A. Babola ◽  
Sally Li ◽  
Zhirong Wang ◽  
Calvin J. Kersbergen ◽  
Ana Belén Elgoyhen ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Early Development ◽  
Auditory System ◽  
Purinergic Signaling

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

2002 ◽  
Vol 283 (2) ◽  
pp. C569-C578 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Release ◽  
Anion Channel ◽  
P2y Receptors ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Medium Osmolarity ◽  
Subsequent Activation

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.

scholarly journals Genome-Wide Transcriptomic Identification and Functional Insight of Lily WRKY Genes Responding to Botrytis Fungal Disease

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 776
Author(s):  
Shipra Kumari ◽  
Bashistha Kumar Kanth ◽  
Ju young Ahn ◽  
Jong Hwa Kim ◽  
Geung-Joo Lee
Keyword(s):  
Abiotic Stress ◽  
Biotic Stress ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Lilium Longiflorum ◽  
Biotic And Abiotic Stress ◽  
Biotic Stresses ◽  
Genome Wide

Genome-wide transcriptome analysis using RNA-Seq of Lilium longiflorum revealed valuable genes responding to biotic stresses. WRKY transcription factors are regulatory proteins playing essential roles in defense processes under environmental stresses, causing considerable losses in flower quality and production. Thirty-eight WRKY genes were identified from the transcriptomic profile from lily genotypes, exhibiting leaf blight caused by Botrytis elliptica. Lily WRKYs have a highly conserved motif, WRKYGQK, with a common variant, WRKYGKK. Phylogeny of LlWRKYs with homologous genes from other representative plant species classified them into three groups- I, II, and III consisting of seven, 22, and nine genes, respectively. Base on functional annotation, 22 LlWRKY genes were associated with biotic stress, nine with abiotic stress, and seven with others. Sixteen unique LlWRKY were studied to investigate responses to stress conditions using gene expression under biotic and abiotic stress treatments. Five genes—LlWRKY3, LlWRKY4, LlWRKY5, LlWRKY10, and LlWRKY12—were substantially upregulated, proving to be biotic stress-responsive genes in vivo and in vitro conditions. Moreover, the expression patterns of LlWRKY genes varied in response to drought, heat, cold, and different developmental stages or tissues. Overall, our study provides structural and molecular insights into LlWRKY genes for use in the genetic engineering in Lilium against Botrytis disease.

Developmental stages influence in vivo antimalarial activity of aerial part extracts of Schkuhria pinnata

2021 ◽  
pp. 114341
Author(s):  
Catherine Nuwagira ◽  
Emanuel L. Peter ◽  
Clement Olusoji Ajayi ◽  
John Adriko ◽  
Kagoro-Rugunda Grace ◽  
...  
Keyword(s):  
Aerial Part ◽  
Developmental Stages ◽  
Antimalarial Activity

scholarly journals Cloning, Characterization, and RNA Interference Effect of the UDP-N-Acetylglucosamine Pyrophosphorylase Gene in Cnaphalocrocis medinalis

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 464
Author(s):  
Yuan-Jin Zhou ◽  
Juan Du ◽  
Shang-Wei Li ◽  
Muhammad Shakeel ◽  
Jia-Jing Li ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Developmental Stages ◽  
Phylogenetic Analyses ◽  
Digital Pcr ◽  
Cnaphalocrocis Medinalis ◽  
Chitin Synthesis ◽  
Reading Frame ◽  
Rnai Technology ◽  
Glyphodes Pyloalis ◽  
Key Enzyme

The rice leaf folder, Cnaphalocrocis medinalis is a major pest of rice and is difficult to control. UDP-N-acetylglucosamine pyrophosphorylase (UAP) is a key enzyme in the chitin synthesis pathway in insects. In this study, the UAP gene from C. medinalis (CmUAP) was cloned and characterized. The cDNA of CmUAP is 1788 bp in length, containing an open reading frame of 1464 nucleotides that encodes 487 amino acids. Homology and phylogenetic analyses of the predicted protein indicated that CmUAP shared 91.79%, 87.89%, and 82.75% identities with UAPs of Glyphodes pyloalis, Ostrinia furnacalis, and Heortia vitessoides, respectively. Expression pattern analyses by droplet digital PCR demonstrated that CmUAP was expressed at all developmental stages and in 12 tissues of C. medinalis adults. Silencing of CmUAP by injection of double-stranded RNA specific to CmUAP caused death, slow growth, reduced feeding and excretion, and weight loss in C. medinalis larvae; meanwhile, severe developmental disorders were observed. The findings suggest that CmUAP is essential for the growth and development of C. medinalis, and that targeting the CmUAP gene through RNAi technology can be used for biological control of this insect.

scholarly journals NF-κB activity during pancreas development regulates adult β-cell mass by modulating neonatal β-cell proliferation and apoptosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dror Sever ◽  
Anat Hershko-Moshe ◽  
Rohit Srivastava ◽  
Roy Eldor ◽  
Daniel Hibsher ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Developmental Stages ◽  
Cell Mass ◽  
Diabetes Incidence ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Regulatory Circuit ◽  
Proliferation And Apoptosis

AbstractNF-κB is a well-characterized transcription factor, widely known for its roles in inflammation and immune responses, as well as in control of cell division and apoptosis. However, its function in β-cells is still being debated, as it appears to depend on the timing and kinetics of its activation. To elucidate the temporal role of NF-κB in vivo, we have generated two transgenic mouse models, the ToIβ and NOD/ToIβ mice, in which NF-κB activation is specifically and conditionally inhibited in β-cells. In this study, we present a novel function of the canonical NF-κB pathway during murine islet β-cell development. Interestingly, inhibiting the NF-κB pathway in β-cells during embryogenesis, but not after birth, in both ToIβ and NOD/ToIβ mice, increased β-cell turnover, ultimately resulting in a reduced β-cell mass. On the NOD background, this was associated with a marked increase in insulitis and diabetes incidence. While a robust nuclear immunoreactivity of the NF-κB p65-subunit was found in neonatal β-cells, significant activation was not detected in β-cells of either adult NOD/ToIβ mice or in the pancreata of recently diagnosed adult T1D patients. Moreover, in NOD/ToIβ mice, inhibiting NF-κB post-weaning had no effect on the development of diabetes or β-cell dysfunction. In conclusion, our data point to NF-κB as an important component of the physiological regulatory circuit that controls the balance of β-cell proliferation and apoptosis in the early developmental stages of insulin-producing cells, thus modulating β-cell mass and the development of diabetes in the mouse model of T1D.

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