Terminal sprouting in mouse neuromuscular junctions poisoned with botulinum type a toxin: Morphological and electrophysiological features

Angaut-Petit, D.; Molgó, Jordi; Comella, Joan X.; Faille, Lucette; Tabti, Nacira

doi:10.1016/0306-4522(90)90109-h

Cited by 116 publications

(65 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…54 There is also evidence forncpuro_2007_279f3.eps subsequent compensatory nerve sprouting and the creation of extrajunctional synapses. [55][56][57][58] When exocytosis at the parent terminal eventually recovers, the nerves retract and endplate functioning returns to normal. 55,59 BTX-A administration has a similar effect on neuroeffector transmission in both smooth and striated muscle.…”

Section: Action On Striated Versus Smooth Musclementioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

View full text Add to dashboard Cite

SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

show abstract

Section: Action On Striated Versus Smooth Musclementioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The affected nerve terminals do not degenerate, and function recovers through axonal sprouting and the formation of new synaptic contacts. 11 The time necessary to recover function from paralysis depends on toxin type and the type of nerve terminals. It usually takes 2-4 months at the mammalian N-M junction, and longer in autonomic neurons, sometimes more than a year.…”

Section: Botulinum Toxin a And Vulvodynia H Yoon Et Almentioning

confidence: 99%

Botulinum toxin A for the management of vulvodynia

2006

View full text Add to dashboard Cite

Clinically, botulinum toxin A blocks the cholinergic innervation of the target tissue. Recently, it has been proved effective not only at a neuromuscular junction but also within parasympathetic or sympathetic neural synapses. Seven women with pain on genitalia that could not be controlled with conventional pain managements were enrolled in this study. Twenty to 40 U of botulinum toxin A were used in each injection. Injection sites were the vestibule, levator ani muscle or the perineal body. Repeat injections were administered every 2 weeks if the patient's symptoms had not fully subsided. In all patients, pain had disappeared with botulinum toxin A injections. Five patients needed to be injected twice; the other two patients needed only one injection. We did not observe complications related to botulinum toxin A injections, such as pain, hemorrhage, infection, muscle paralysis or other complications. The subjective pain score improved from 8.3 to 1.4, and no one has experienced a recurrence (the follow-up period was four to 24 months, with a mean follow-up of 11.6 months). Botulinum toxin A is effective in blocking nociception. Even though further investigation and well-controlled study will be necessary, we suggest that the botulinum toxin therapy would be useful and safe in managing vulvodynia of muscular or neuroinflammatory origins.

show abstract

“…The ability of nerve endings at the neuromuscular junction to sprout after the potent blockade of neurotransmission by botulinum neurotoxin type A (BoTx͞A) is a striking example of synaptic plasticity (1)(2)(3)(4). Although significant progress already has been made in identifying the factors triggering such outgrowth (see ref.…”

mentioning

confidence: 99%

“…7 and 8) causes an unique and long-term eradication of synaptic activity, while, advantageously, avoiding removal of the nerve endings (9,10). Despite the extent of the paralysis induced by this toxin, recovery of neurotransmission does occur eventually, as manifested in animal experiments (2,(11)(12)(13) and in the clinical treatment of dystonias involving involuntary movement of certain skeletal muscles (see ref. 14).…”

mentioning

confidence: 99%

Functional repair of motor endplates after botulinum neurotoxin type A poisoning: Biphasic switch of synaptic activity between nerve sprouts and their parent terminals

Paiva

Meunier

Molgó

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

604

414

View full text Add to dashboard Cite

Blockade of acetylcholine release by botulinum neurotoxin type A at the neuromuscular junction induces the formation of an extensive network of nerve-terminal sprouts. By repeated in vivo imaging of N-(3-triethyl ammonium propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide uptake into identified nerve endings of the mouse sternomastoid muscle after a single intramuscular injection of the toxin, inhibition of stimulated uptake of the dye at the terminals was detected within a few days, together with an increase in staining of the newly formed sprouts. After 28 days, when nerve stimulation again elicited muscle contraction, regulated vesicle recycling occurred only in the sprouts [shown to contain certain soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAREs) and to abut acetylcholine receptors] and not at the parent terminals. Therefore, only these sprouts could be responsible for nerve-muscle transmission at this time. However, a second, distinct phase of the rehabilitation process followed with a return of vesicle turnover to the original terminals, accompanied by an elimination of the by then superf luous sprouts. This extension and later removal of ''functional'' sprouts indicate their fundamental importance in the repair of paralyzed endplates, a finding with ramifications for the vital process of nerve regeneration.The ability of nerve endings at the neuromuscular junction to sprout after the potent blockade of neurotransmission by botulinum neurotoxin type A (BoTx͞A) is a striking example of synaptic plasticity (1-4). Although significant progress already has been made in identifying the factors triggering such outgrowth (see ref. 5), as well as that induced on, for example, partial denervation by nerve crush (1, 6), the significance of endplate remodeling in the intricate series of interactions between presynaptic and postsynaptic cells during recovery of transmission at paralyzed synapses has yet to be shown. The selective blockade of the regulated exocytosis of acetylcholine (ACh) by BoTx͞A after its intracellular proteolytic cleavage of synaptosomal-associated protein with a molecular mass of 25 kDa ref. 7 and 8) causes an unique and long-term eradication of synaptic activity, while, advantageously, avoiding removal of the nerve endings (9, 10). Despite the extent of the paralysis induced by this toxin, recovery of neurotransmission does occur eventually, as manifested in animal experiments (2, 11-13) and in the clinical treatment of dystonias involving involuntary movement of certain skeletal muscles (see ref. 14). Although BoTx͞A is known to promote nerve sprouting, it has remained unclear what the precise contribution, if any, these newly formed outgrowths make to the recovery from this initially dramatic, but ultimately temporary, paralysis.Limitations encountered in earlier studies on this fundamentally important question originated from the need to employ conventional histological techniques in vitro to excised tissues. These limitations have been overcome in our stu...

show abstract

Terminal sprouting in mouse neuromuscular junctions poisoned with botulinum type a toxin: Morphological and electrophysiological features

Cited by 116 publications

References 43 publications

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Botulinum toxin A for the management of vulvodynia

Functional repair of motor endplates after botulinum neurotoxin type A poisoning: Biphasic switch of synaptic activity between nerve sprouts and their parent terminals

Contact Info

Product

Resources

About