scholarly journals Lose it to use it

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Seth G. Haddix ◽  
Matthew N. Rasband
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Activity ◽  
Motor Axon ◽  
Trophic Factors ◽  
Synapse Elimination ◽  
Anterograde Transport ◽  
Neuregulin 1 ◽  
Synaptic Pruning

In this issue, Wang et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.201911114) describe a phenomenon in which neuromuscular junction synapse elimination triggers myelination of terminal motor axon branches. They propose a mechanism initiated by synaptic pruning that depends on synaptic activity, cytoskeletal maturation, and the associated anterograde transport of trophic factors including Neuregulin 1-III.

scholarly journals The ketogenic diet increases Neuregulin 1 expression via elevating histone acetylation and its anti-seizure effect requires ErbB4 kinase activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Wang ◽  
Jie Huang ◽  
Shan Yao ◽  
Jia-Hui Wu ◽  
Hui-Bin Li ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Ketogenic Diet ◽  
Chromatin Immunoprecipitation ◽  
Kinase Activity ◽  
Control Diet ◽  
Synaptic Activity ◽  
Therapeutic Interventions ◽  
Type I ◽  
Neuregulin 1

Abstract Background The ketogenic diet (KD)has been considered an effective treatment for epilepsy, whereas its underlying mechanisms remain obscure. We have previously reported that the KD feeding increased Neuregulin 1 (NRG1) expression in the hippocampus; disruption of NRG1 signaling by genetically deleting its receptor-ErbB4 abolished KD’s effects on inhibitory synaptic activity and seizures. However, it is still unclear about the mechanisms underlying the effect of KD on NRG1 expression and whether the effects of KD require ErbB4 kinase activity. Methods The effects of the KD on NRG1 expression were assessed via western blotting and real-time PCR. Acetylation level at the Nrg1 promoter locus was examined using the chromatin immunoprecipitation technique. Kainic acid (KA)-induced acute seizure model was utilized to examine the effects of KD and histone deacetylase inhibitor-TSA on seizures. Synaptic activities in the hippocampus were recorded with the technique of electrophysiology. The obligatory role of ErbB4 kinase activity in KD’s effects on seizures and inhibitory synaptic activity was evaluated by using ErbB kinase antagonist and transgenic mouse-T796G. Results We report that KD specifically increases Type I NRG1 expression in the hippocampus. Using the chromatin immunoprecipitation technique, we observe increased acetylated-histone occupancy at the Nrg1 promoter locus of KD-fed mice. Treatment of TSA dramatically elevates NRG1 expression and diminishes the difference between the effects of the control diet (CD) and KD. These data indicate that KD increases NRG1 expression via up-regulating histone acetylation. Moreover, both pharmacological and genetic inhibitions of ErbB4 kinase activity significantly block the KD’s effects on inhibitory synaptic activity and seizure, suggesting an essential role of ErbB4 kinase activity. Conclusion These results strengthen our understanding of the role of NRG1/ErbB4 signaling in KD and shed light on novel therapeutic interventions for epilepsy.

Facilitation at the Lobster Neuromuscular Junction: A Stimulus-Dependent Mobilization Model

1997 ◽  
Vol 78 (1) ◽  
pp. 417-428 ◽  
Author(s):  
Mary Kate Worden ◽  
Maria Bykhovskaia ◽  
John T. Hackett
Keyword(s):  
Neuromuscular Junction ◽  
Kinetic Equations ◽  
Nerve Impulse ◽  
Stimulation Frequency ◽  
Synaptic Activity ◽  
Quantal Content ◽  
Physiological Basis ◽  
Low Frequencies ◽  
Average Probability ◽  
Frequency Facilitation

Worden, Mary Kate, Maria Bykhovskaia, and John T. Hackett. Facilitation at the lobster neuromuscular junction: a stimulus-dependent mobilization model. J. Neurophysiol. 78: 417–428, 1997. Frequency facilitation is a process whereby neurosecretion increases as a function of stimulation frequency during repetitive synaptic activity. To examine the physiological basis underlying facilitation, we have estimated the frequency dependence of the synaptic parameters n (number of units capable of responding to a nerve impulse) and P (average probability of responding) at the lobster neuromuscular junction. Both n and P increase as a function of frequency, suggesting that the efficiency of quantal docking and quantal fusion is regulated by repetitive synaptic activity. In experiments in which facilitation is strong and quantal content does not saturate over the frequency range tested, the value of P saturates at low frequencies of stimulation, and increases in quantal content at higher frequencies of stimulation are due to an increase in n. Therefore the value of P does not limit facilitation. We propose that transmitter release is limited by the rates of quantal mobilization and demobilization, and that each excitatory stimulus causes additional mobilization of quanta to dock at the presynaptic release sites. In such a model the binomial parameter n will correspond to the number of quanta docked at the release sites and available for release. We have developed and solved kinetic equations that describe how the number of docked quanta changes as a function of time and of stimulation frequency. The stimulus-dependent mobilization model of facilitation predicts that the reciprocal value of the quantal content depends linearly on the reciprocal product of the stimulation frequency and the probability of release. Fits of the experimental data confirm the accuracy of this prediction, showing that the model proposed here quantitatively describes frequency facilitation. The model predicts that high rates of quantal demobilization will produce strong frequency facilitation.

TGFβ Trophic Factors Differentially Modulate Motor Axon Outgrowth and Protection from Excitotoxicity

2000 ◽  
Vol 161 (2) ◽  
pp. 664-675 ◽  
Author(s):  
Tony W. Ho ◽  
Lynn A. Bristol ◽  
Carol Coccia ◽  
Yun Li ◽  
Jeffrey Milbrandt ◽  
...  
Keyword(s):  
Axon Outgrowth ◽  
Motor Axon ◽  
Trophic Factors

scholarly journals Native chick laminin-4 containing the beta 2 chain (s-laminin) promotes motor axon growth.

1996 ◽  
Vol 135 (6) ◽  
pp. 1583-1592 ◽  
Author(s):  
R Brandenberger ◽  
R A Kammerer ◽  
J Engel ◽  
M Chiquet
Keyword(s):  
Basement Membrane ◽  
Neuromuscular Junction ◽  
Coiled Coil ◽  
Axon Growth ◽  
Motor Axon ◽  
Specific Sequence ◽  
Recombinant Fragment ◽  
Structural Context ◽  
Coiled Coil Region ◽  
Beta 2

After denervation of muscle, motor axons reinnervate original synaptic sites. A recombinant fragment of the synapse specific laminin beta 2 chain (s-laminin) was reported to inhibit motor axon growth. Consequently, a specific sequence (leucine-arginine-glutamate, LRE) of the laminin beta 2 chain was proposed to act as a stop signal and to mediate specific reinnervation at the neuromuscular junction (Porter, B.E., J. Weis, and J.R. Sanes. 1995. Neuron. 14:549-559). We demonstrate here that native chick laminin-4, which contains the beta 2 chain and is present in the synaptic basement membrane, does not inhibit but rather promotes motor axon growth. In native heterotrimeric laminin, the LRE sequence of the beta 2 chain is found in a triple coiled-coil region that is formed by all three subunits. We show here that the effect of LRE depends on the structural context. Whereas a recombinant randomly coiled LRE peptide indeed inhibited outgrowth by chick motoneurons, a small recombinant triple coiled-coil protein containing this sequence did not.

scholarly journals Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning

2018 ◽  
Vol 115 (24) ◽  
pp. 6303-6308 ◽  
Author(s):  
Balázs A. Györffy ◽  
Judit Kun ◽  
György Török ◽  
Éva Bulyáki ◽  
Zsolt Borhegyi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Sensory Deprivation ◽  
Complement Cascade ◽  
Synapse Elimination ◽  
Microglial Phagocytosis ◽  
Synapse Loss ◽  
Preferential Localization ◽  
Proteomic Investigation ◽  
Apoptosis Markers ◽  
Synaptic Pruning

C1q, a member of the immune complement cascade, is implicated in the selective pruning of synapses by microglial phagocytosis. C1q-mediated synapse elimination has been shown to occur during brain development, while increased activation and complement-dependent synapse loss is observed in neurodegenerative diseases. However, the molecular mechanisms underlying C1q-controlled synaptic pruning are mostly unknown. This study addresses distortions in the synaptic proteome leading to C1q-tagged synapses. Our data demonstrated the preferential localization of C1q to the presynapse. Proteomic investigation and pathway analysis of C1q-tagged synaptosomes revealed the presence of apoptotic-like processes in C1q-tagged synapses, which was confirmed experimentally with apoptosis markers. Moreover, the induction of synaptic apoptotic-like mechanisms in a model of sensory deprivation-induced synaptic depression led to elevated C1q levels. Our results unveiled that C1q label-based synaptic pruning is triggered by and directly linked to apoptotic-like processes in the synaptic compartment.

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