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Article ; Online: Pre- and post-synaptic roles of action potential activity in synapse elimination revealed by using ectopic neuromuscular junction formation by a foreign nerve.

Busetto, Giuseppe / Cangiano, Alberto

2020 Volume 722, Page(s) 134835

Abstract: The formation of the neuromuscular junction (nmj) is based on molecular cascades initiated by neural agrin as well as electrical activity in the neuromuscular structures. This review focuses on the latter factor, emphasizing the multiplicity of its ... ...

Abstract	The formation of the neuromuscular junction (nmj) is based on molecular cascades initiated by neural agrin as well as electrical activity in the neuromuscular structures. This review focuses on the latter factor, emphasizing the multiplicity of its mechanisms in the process of synapse elimination following initial polyneuronal innervation. Pre- and post-synaptic components of activity have in fact been identified through experiments on an adult model of nmj formation: ectopic reinnervation of the rat soleus muscle by the fibular nerve. Two activity-dependent elimination processes are thus compared: competition between distributed nmjs, which depends on evoked muscle impulse activity, and competition between axons converging on single nmjs, which instead depends on differences in the timing of impulses in the converging axons.
MeSH term(s)	Action Potentials/physiology ; Animals ; Choristoma/physiopathology ; Humans ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/innervation ; Muscle, Skeletal/physiology ; Neuromuscular Junction/physiology ; Synapses/physiology
Language	English
Publishing date	2020-02-10
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2020.134835
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Article ; Online: Activity-dependent vs. neurotrophic modulation of acetylcholine receptor expression: Evidence from rat soleus and extensor digitorum longus muscles confirms the exclusive role of activity.

Buffelli, Mario / Tognana, Enrico / Cangiano, Alberto / Busetto, Giuseppe

The European journal of neuroscience

2018 Volume 47, Issue 12, Page(s) 1474–1481

Abstract: Evoked electrical muscle activity suppresses the transcription of mRNAs for acetylcholine receptors in extrajunctional myonuclei. Muscle denervation or disuse releases such inhibition and extrajunctional receptors appear. However, in soleus muscles ... ...

Abstract	Evoked electrical muscle activity suppresses the transcription of mRNAs for acetylcholine receptors in extrajunctional myonuclei. Muscle denervation or disuse releases such inhibition and extrajunctional receptors appear. However, in soleus muscles paralysed with nerve-applied tetrodotoxin, a restricted perijunctional region has been described where myonuclei remain inhibited, a finding attributed to nerve-derived trophic factor(s). Here, we reinvestigate extrajunctional acetylcholine receptor expression in soleus and extensor digitorum longus muscles up to 90 days after denervation or up to 20 days of disuse, to clarify the role of trophic factors, if any. The perijunctional region of soleus muscles strongly expressed acetylcholine receptors during the first 2-3 weeks of denervation. After 2-3 months, this expression had disappeared. No perijunctional expression was seen after paralysis by tetrodotoxin or botulinum toxin A. In contrast, the extensor digitorum longus never displayed suppressed perijunctional acetylcholine receptor expression after any treatment, suggesting that it is an intrinsic property of soleus muscles. Soleus denervation only transiently removed the suppression, and its presence in long-term denervated soleus muscles contradicts any contribution from nerve-derived trophic factor(s). In conclusion, our results confirm that evoked electrical activity is the physiological factor controlling the expression of acetylcholine receptors in the entire extrajunctional membrane of skeletal muscles.
MeSH term(s)	Acetylcholine Release Inhibitors/pharmacology ; Animals ; Autoradiography ; Electrophysiological Phenomena/physiology ; Male ; Motor Activity/physiology ; Muscle Denervation ; Muscle, Skeletal/innervation ; Muscle, Skeletal/metabolism ; Nerve Growth Factors/metabolism ; Rats ; Rats, Wistar ; Receptors, Cholinergic/metabolism ; Sodium Channel Blockers/pharmacology
Chemical Substances	Acetylcholine Release Inhibitors ; Nerve Growth Factors ; Receptors, Cholinergic ; Sodium Channel Blockers
Language	English
Publishing date	2018-06-26
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.14020
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Article ; Online: The Impact of Venous Thromboembolism on Upper Tract Urothelial Carcinomas Undergoing Open or Minimally Invasive Radical Nephroureterectomy in the USA: Perioperative Outcomes and Health Care Costs from Insurance Claims Data.

Tresh, Anas S / Del Giudice, Francesco / Li, Shufeng / Basran, Satvir / Belladelli, Federico / De Berardinis, Ettore / Asero, Vincenzo / Ferro, Matteo / Tataru, Sabin / Maria Busetto, Gian / Falagario, Ugo / Autorino, Riccardo / Crocetto, Felice / Barone, Biagio / Pradere, Benjamin / Moschini, Marco / Mari, Andrea / Krajewski, Wojciech / Nowak, Łukasz /

Małkiewicz, Bartosz / Szydełko, Tomasz / Crivellaro, Simone / Rane, Abhay / Challacombe, Benjamin / Nair, Rajesh / Chung, Benjamin I

European urology focus

2024

Abstract: Background and objective: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing ...

Abstract	Background and objective: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Our aim was to assess the impact of a preoperative VTE diagnosis on perioperative outcomes in the RNU context. Methods: Patients aged 18 yr or older with a UTUC diagnosis undergoing RNU were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of VTE prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism [PE] and/or deep venous thrombosis [DVT]) was examined. Key findings and limitations: Within the investigated cohort of 6922 patients, history of any VTE preceding RNU was reported in 568 (8.21%) cases, including DVT (n = 290, 51.06%), PE (n = 169, 29.75%), and superficial VTE (n = 109, 19.19%). The history of VTE before RNU was predictive of higher rates of complications, the most prevalent being respiratory complications (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.43-2.22). Preoperative VTE was found to be associated with an increased risk of VTE following RNU (OR: 14.3, 95% CI: 11.48-17.82), higher rehospitalization rates (OR: 1.26, 95% CI 1.01-1.56) other than home discharge status (OR: 1.44, 95% CI: 1.18-1.77), and higher costs (OR 1.42, 95% CI: 1.20-1.68). Limitations include the retrospective nature and the use of an insurance database that relies on accurate coding and does not include information such as pathologic staging. Conclusions and clinical implications: The presented findings will contribute to the counseling process for patients. These patients may benefit from enhanced pre/postoperative anticoagulation. More research is needed before the following results can be used in the clinical setting. Patient summary: Patients aged 18 yr or older with an upper tract urothelial carcinoma (UTUC) diagnosis undergoing radical nephroureterectomy (RNU) were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of venous thromboembolism (VTE) prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism and/or deep venous thrombosis) was examined. The presented findings will contribute to the counseling of patients with UTUC and preoperative VTE.
Language	English
Publishing date	2024-03-02
Publishing country	Netherlands
Document type	Journal Article
ISSN	2405-4569
ISSN (online)	2405-4569
DOI	10.1016/j.euf.2024.02.004
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Article ; Online: The timing of impulse activity shapes the process of synaptic competition at the neuromuscular junction.

Favero, M / Buffelli, M / Cangiano, A / Busetto, G

Neuroscience

2010 Volume 167, Issue 2, Page(s) 343–353

Abstract: The development of neuromuscular junctions exhibits profound remodeling that brings from an immature state characterized by multiple motoneuronal inputs per muscle fiber, to a mature mononeuronal innervation. This striking elimination process occurs both ...

Abstract	The development of neuromuscular junctions exhibits profound remodeling that brings from an immature state characterized by multiple motoneuronal inputs per muscle fiber, to a mature mononeuronal innervation. This striking elimination process occurs both perinatally and during adult reinnervation, and is also widely present in the developing CNS. The accelerating influence of the amount of impulse activity on this process, has been shown by various studies, but a more subtle role of the time correlation of action potential firing in the competing inputs, has also been suggested. Here we explore the latter influence using a rat adult model of neuromuscular junction formation, that is reinnervation following a motor nerve crush. This shares all important features with perinatal development, especially the strict juxtaposition of the competing inputs. In fact the regenerating axons converge on a single cluster of postsynaptic receptors, that is the original endplate of each muscle fiber. This focus on the spatial aspect of competition between nerve endings was missing in our previous experiments employing a similar paradigm. We impose a chronic synchronous firing to the competing terminals, by in vivo electrical stimulation of their axons distal to a sciatic nerve conduction block. Control preparations, with similar post-crush reinnervation, are left with their natural impulse activity unperturbed. We find that the experimental muscles display a prolonged duration of polyneuronal innervation with respect to controls, indicating that hebbian mechanisms participate in the synapse elimination process. Another aspect dealt with in our study is the genuine nature of the polyneuronal innervation occurring during adult muscle reinnervation, because it is supported by both confocal microscopy and by appropriate electrophysiological tests that exclude electrical coupling of myofibers by gap junctions.
MeSH term(s)	Animals ; Electric Stimulation ; Male ; Membrane Potentials ; Motor Endplate/physiology ; Motor Neurons/physiology ; Muscle, Skeletal/innervation ; Nerve Crush ; Nerve Fibers/physiology ; Neuromuscular Junction/physiology ; Peripheral Nerves/physiology ; Rats ; Rats, Wistar ; Synapses/physiology
Language	English
Publishing date	2010-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2010.01.055
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Article ; Online: Adult rat motor neurons do not re-establish electrical coupling during axonal regeneration and muscle reinnervation.

Favero, Morgana / Cangiano, Alberto / Busetto, Giuseppe

PloS one

2015 Volume 10, Issue 4, Page(s) e0123576

Abstract: Gap junctions (GJs) between neurons are present in both the newborn and the adult nervous system, and although important roles have been suggested or demonstrated in a number of instances, in many other cases a full understanding of their physiological ... ...

Abstract	Gap junctions (GJs) between neurons are present in both the newborn and the adult nervous system, and although important roles have been suggested or demonstrated in a number of instances, in many other cases a full understanding of their physiological role is still missing. GJs are expressed in the rodent lumbar cord at birth and mediate both dye and electrical coupling between motor neurons. This expression has been proposed to mediate: (i) fast synchronization of motoneuronal spike activity, in turn linked to the process of refinement of neuromuscular connections, and (ii) slow synchronization of locomotor-like oscillatory activity. Soon after birth this coupling disappears. Since in the adult rat regeneration of motor fibers after peripheral nerve injury leads to a recapitulation of synaptic refinement at the target muscles, we tested whether GJs between motor neurons are transiently re-expressed. We found that in conditions of maximal responsiveness of lumbar motor neurons (such as no depression by anesthetics, decerebrate release of activity of subsets of motor neurons, use of temporal and spatial summation by antidromic and orthodromic stimulations, testing of large ensembles of motor neurons) no firing is observed in ventral root axons in response to antidromic spike invasion of nearby counterparts. We conclude that junctional coupling between motor neurons is not required for the refinement of neuromuscular innervation in the adult.
MeSH term(s)	Action Potentials ; Animals ; Axons/physiology ; Electrophysiological Phenomena ; Hindlimb/innervation ; Hindlimb/physiopathology ; Male ; Motor Neurons/physiology ; Muscles/innervation ; Muscles/physiopathology ; Nerve Crush ; Nerve Regeneration/physiology ; Rats, Wistar ; Sciatic Nerve/physiopathology ; Time Factors
Language	English
Publishing date	2015-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0123576
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Article: Lesson from the neuromuscular junction: role of pattern and timing of nerve activity in synaptic development.

Favero, Morgana / Cangiano, Alberto / Busetto, Giuseppe

Neural regeneration research

2015 Volume 10, Issue 5, Page(s) 686–688

Language	English
Publishing date	2015-04-08
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.156944
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Article ; Online: Hebb-based rules of neural plasticity: are they ubiquitously important for the refinement of synaptic connections in development?

Favero, Morgana / Cangiano, Alberto / Busetto, Giuseppe

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

2014 Volume 20, Issue 1, Page(s) 8–14

Abstract: Neuronal death and suppression of functional synaptic inputs are well-known regressive events characterizing PNS and CNS development. In the CNS, participation of activity in synapse elimination has been known ever since the pioneering studies of Hubel ... ...

Abstract	Neuronal death and suppression of functional synaptic inputs are well-known regressive events characterizing PNS and CNS development. In the CNS, participation of activity in synapse elimination has been known ever since the pioneering studies of Hubel and Wiesel, but only recently has a Hebb-based mechanism of spike synchrony versus asynchrony received unequivocal experimental support in the visual system. At the neuromuscular junction (NMJ), where synapse elimination was discovered, the specific function of the "timing of activity" was addressed by only one group of studies and did not receive widespread attention. Here we critically review the latest NMJ investigation advocating an "activity-independent" mechanism for synapse elimination and contrast it with an equally recent study demonstrating a key role for spike timing. Finally, we highlight how the striking similarities between the two mentioned studies on spike timing (visual system and NMJ) establish conclusively its role in the development of the nervous system in general.
MeSH term(s)	Action Potentials/physiology ; Animals ; Brain/growth & development ; Brain/physiology ; Humans ; Nerve Degeneration ; Neuromuscular Junction/growth & development ; Neuromuscular Junction/physiology ; Neuronal Plasticity/physiology ; Synapses/physiology
Language	English
Publishing date	2014-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1233753-5
ISSN	1089-4098 ; 1073-8584
ISSN (online)	1089-4098
ISSN	1073-8584
DOI	10.1177/1073858413491148
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Article ; Online: How urinary stone emergencies changed in the time of COVID-19?

Flammia, S. / Salciccia, S. / Tufano, A. / Busetto, G. M. / Ricciuti, G. P. / Sciarra, A.

2020

Abstract: The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named COVID-19 [1], is generating a severe health emergency all over the world but particularly in some countries. The healthcare challenge is to provide assistance to the increasing ... ...

Abstract	The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named COVID-19 [1], is generating a severe health emergency all over the world but particularly in some countries. The healthcare challenge is to provide assistance to the increasing number of infected patients, to contain ways of transmission and at the same time to treat all the non-deferrable medical conditions that continue to affect the population. Moreover, the most relevant problems are in the management of all first aid accesses and emergencies other than COVID-19. In this brief communication, we report our experience on the diagnostic and therapeutic procedures requested and performed for urinary stone emergencies during a 6-week period activity in a hospital partially converted to COVID-19 care and in the highest national level of COVID-19 infection (March–April 2020), with the management performed in the same hospital in a no-COVID-19 period (March–April 2019) 1 year ago. In particular, we analyzed differences between these two time-related populations in terms of patients and urinary stone characteristics, symptoms and complications at presentation, diagnostic and therapeutic approaches, time of hospitalization. ANOVA analysis and Chi square test were used to quantify the differences between the two time periods. Some relevant data are obtained (Table (Table1):1): (1) independent to COVID-19 infection, in our hospital, the number of first aid accesses for urinary stone emergencies did not significantly change (44 cases in the no COVID-19 period versus 36 cases in the COVID-19 period) (2) patients presenting during COVID-19 time showed significantly higher serum levels of creatinine (p = 0.026) when compared to a no-COVID-19 period. These data may suggest a delay in terms of patient presentation to the hospital, related to the pandemic. (3) However, no significant differences were detected in terms of complication rates, urinary stone diameter or grade of hydronephrosis due to COVID-19 pandemic. (4) Stone position significantly changed with a higher rate of lumbar ureter and lower of juxta-vesical site during COVID-19 period (p = 0.036). The reduction of first aid access for juxta-vesical site stones may be interpreted through a higher rate of its management using medical therapies at home. (5) Diagnostic and therapeutic approach to urinary stone emergencies did not significantly change compared to the non-pandemic period. In particular, the use of nephrostomy or ureteral stent for the first aid did not significantly change. Across a 6-week period during the peak of the COVID-19 pandemic, urinary stone emergencies continued to be managed with few significant variations in a geographical area at medium density for COVID-19 and in a hospital partially converted in first aid cares
Keywords	urolithiasis ; covid ; covid19
Subject code	333
Language	English
Publisher	Springer
Publishing country	it
Document type	Article ; Online
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Article ; Online: The timing of activity is a regulatory signal during development of neural connections.

Favero, Morgana / Cangiano, Alberto / Busetto, Giuseppe

Journal of molecular neuroscience : MN

2013 Volume 53, Issue 3, Page(s) 324–329

Abstract: In PNS and CNS remarkable rearrangements occur soon after the connections are laid down in the course of embryonic life. These processes clearly follow the period of developmental cell death and mostly take place during the very beginning of postnatal ... ...

Abstract	In PNS and CNS remarkable rearrangements occur soon after the connections are laid down in the course of embryonic life. These processes clearly follow the period of developmental cell death and mostly take place during the very beginning of postnatal life. They consist in changes of the peripheral fields of neurons, marked by elimination of many inputs, while others undergo further maturation and strengthening. Along the efforts to uncover the signals that regulate development, it turned out that while the initial construction of the circuits is heavily based on chemical cues, the subsequent rearrangement is markedly influence by activity. Here we describe experiments testing the influence on developmental plasticity of a particular aspect of activity, the timing of nerve impulses in the competing inputs. Two recent investigations are reviewed, indicating strikingly similar developmental features in quite different systems, neuromuscular and visual. A sharp contrast between the effects of synchrony and asynchrony emerges, indicating that Hebb-related activity rules are important not only for learning but also for development.
MeSH term(s)	Animals ; Humans ; Motor Neurons/physiology ; Neuromuscular Junction/growth & development ; Neuromuscular Junction/physiology ; Retinal Ganglion Cells/physiology ; Synaptic Potentials
Language	English
Publishing date	2013-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1043392-2
ISSN	1559-1166 ; 0895-8696
ISSN (online)	1559-1166
ISSN	0895-8696
DOI	10.1007/s12031-013-0128-z
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Zs.A 3006: Show issues

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Article ; Online: Endocannabinoid-dependent disinhibition of orexinergic neurons: Electrophysiological evidence in leptin-knockout obese mice.

Becker, Thorsten Michael / Favero, Morgana / Di Marzo, Vincenzo / Cristino, Luigia / Busetto, Giuseppe

Molecular metabolism

2017 Volume 6, Issue 6, Page(s) 594–601

Abstract: Objectives: In the : Methods: We performed : Results: We found that OX neurons of : Conclusions: ... ...

Abstract	Objectives: In the Methods: We performed Results: We found that OX neurons of Conclusions: In
MeSH term(s)	Animals ; Arachidonic Acids/pharmacology ; Cannabinoid Receptor Agonists/pharmacology ; Endocannabinoids/pharmacology ; Glycerides/pharmacology ; Leptin/genetics ; Mice ; Mice, Obese ; Neurons/drug effects ; Neurons/metabolism ; Neurons/physiology ; Orexins/genetics ; Orexins/metabolism ; Synaptic Potentials
Chemical Substances	Arachidonic Acids ; Cannabinoid Receptor Agonists ; Endocannabinoids ; Glycerides ; Leptin ; Orexins ; glyceryl 2-arachidonate (8D239QDW64)
Language	English
Publishing date	2017-04-22
Publishing country	Germany
Document type	Journal Article
ISSN	2212-8778
ISSN (online)	2212-8778
DOI	10.1016/j.molmet.2017.04.005
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