Nerve terminal sprouting in botulinum type-A treated mouse levator auris longus muscle

doi:10.1016/0960-8966(96)00041-7

Neuromuscular Disorders

Volume 6, Issue 3, May 1996, Pages 177-185

https://doi.org/10.1016/0960-8966(96)00041-7 Get rights and content

Abstract

The marked outgrowth of the motor nerve terminal arborization triggered by an in vivo local injection of Clostridium botulinum type-A toxin in the mouse levator auris longus muscle was studied with morphological and immunochemical approaches. The increase in total nerve terminal length depended on the time elapsed after toxin administration and was due to both increased number of terminal branches and branch length as revealed by a quantitative morphological analysis of whole mounts using the combined cholinesterase-silver stain. Nerve terminal sprouts increased in number, length and complexity even after the functional recovery of neuromuscular transmission had occurred as revealed by electrophysiological examination. Although we cannot exclude that transmitter release sites from the original nerve terminal arborization may still be functional after botulinum type-A toxin (BoTx-A) treatment, it is likely that newly formed functional release sites on the sprouts play a major role in the functional recovery of neuromuscular transmission. The presence of an immunoreactivity to synaptophysin and synaptotagmin-II, integral proteins of synaptic vesicles, gives support to our previous findings suggesting that nerve terminal sprouts have the molecular machinery for acetylcholine release.

References (36)

H. Niemann et al.
Clostridial neurotoxins: new tools for dissecting exocytosis
Trends in Cell Biol
(1994)
A. Pestronk et al.
Motor nerve outgrowth: reduced capacity for sprouting in the terminals of longer axons
Brain Res
(1988)
D. Angaut-Petit et al.
Terminal sprouting in mouse neuromuscular junctions poisoned with botulinum type A toxin: morphological and electrophysiological features
Neuroscience
(1990)
A.B. Scott
Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery
Ophthalmology
(1980)
D. Angaut-Petit et al.
Mouse motor nerve terminal immunoreactivity to synaptotagmin II during sustained quantal transmitter release
Brain Res
(1995)
P.H. Bonner et al.
Botulinum A toxin stimulates branching in nerve-muscle cocultures
Dev Brain Res
(1994)
J.X. Comella et al.
Sprouting of mammalian motor nerve terminals induced by in vivo injection of botulinum type D toxin and the functional recovery of paralysed neuromuscular junctions
Neurosci Lett
(1993)
A. Wernig et al.
Sprouting and remodelling at the nerve-muscle junction
Prog Neurobiol
(1986)
A.L. Connold et al.
Neuromuscular contacts of expanded motor units in rat soleus muscle are rescued by leupeptin
Neuroscience
(1994)
S.M. Hassan et al.
Calcitonin gene-related peptide like immunoreactivity, in botulinum toxin-paralysed rat muscles
Neuromusc Disord
(1994)

L.W. Duchen

An electron microscopic study of the changes induced by botulinum toxin in the motor end-plates of slow and fast skeletal muscle fibres of the mouse

J Neurol Sci

(1971)

E. Habermann et al.

Clostridial neurotoxins: handling and action at the cellular and molecular level

Curr Top Microbiol Immunol

(1986)

J. Molgó et al.

Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions

J Physiol (Paris)

(1990)

C. Montecucco et al.

Mechanism of action of tetanus and botulinum neurotoxins

Mol Microbiol

(1994)

B. Poulain et al.

Quantal neurotransmitter release and the clostridial neurotoxins' targets

Curr Top Microbiol Immunol

(1995)

L.W. Duchen et al.

The effects of botulinum toxin on the pattern of innervation of skeletal muscle in the mouse

Quart J Exp Physiol

(1968)

E.J. Schantz et al.

Properties and use of botulinum toxin and other microbial neurotoxins in medicine

Microbiol Rev

(1992)

J. Jankovic et al.

Therapeutic uses of botulinum toxin

New Engl J Med

(1991)

Cited by (79)

The binding of botulinum neurotoxins to different peripheral neurons
2018, Toxicon
Citation Excerpt :
the mechanisms of the recovery of motor and of the autonomic nerve terminals could be different and could depend on different mediators. It is long known that the BoNT poisoned NMJ undergoes a profound remodelling with novel nerve terminals, which sprout from their unmyelinated motor axon terminal and, to a lesser extent, from the first node of Ranvier (Duchen, 1971; Juzans et al., 1996; Meunier et al., 2002). The sprouts are guided by proliferating perisynaptic Schwann cells and eventually reach novel muscle fibres to form new nerve-muscle contacts even though are poorly efficient in ACh release (Rogozhin et al., 2008), providing a limited contribution to the recovery of the neurotransmission from nerve to the muscle fibre.
Botulinum neurotoxins are the most potent toxins known. The double receptor binding modality represents one of the most significant properties of botulinum neurotoxins and largely accounts for their incredible potency and lethality. Despite the high affinity and the very specific binding, botulinum neurotoxins are versatile and multi-tasking toxins. Indeed they are able to act both at the somatic and at the autonomic nervous system.
In spite of the preference for cholinergic nerve terminals botulinum neurotoxins have been shown to inhibit to some extent also the noradrenergic postganglionic sympathetic nerve terminals and the afferent nerve terminals of the sensory neurons inhibiting the release of neuropeptides and glutamate, which are responsible of nociception. Therefore, there is increasing evidence that the therapeutic effect in both motor and autonomic disorders is based on a complex mode of botulinum neurotoxin action modulating the activity of efferent as well as afferent nerve fibres.
Clostridial neurotoxins: From the cellular and molecular mode of action to their therapeutic use
2015, The Comprehensive Sourcebook of Bacterial Protein Toxins
Botulinum (BoNT) and tetanus (TeNT) neurotoxins are potent toxins responsible for flaccid and spastic paralysis, respectively. BoNTs are divided into types and subtypes according to their immunological properties and amino acid sequence variations, whereas only one type of TeNT has been characterized. BoNTs associate with nontoxic proteins to form large complexes that are resistant to acidic pH and protease degradation, unlike TeNT, which is produced as a unique protein. BoNTs and TeNT enter target neuronal cells by interacting with specific cell surface receptors. BoNTs proteolytically cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins (SNAP-25, VAMP, or syntaxin) mainly at the cholinergic neuromuscular junctions impairing the evoked release of acetylcholine, whereas TeNT inhibits the neuroexocytosis in central inhibitory interneurons by cleavage of VAMP. BoNT-mediated muscle paralysis induces neuronal sprouting, which after various time periods, leads to a recovery of neurotransmission. BoNT/A, which has a long duration of activity, is used in numerous medical applications.
Effect of botulinum toxin injection on length and lengthening velocity of rectus femoris during gait in hemiparetic patients
2013, Clinical Biomechanics
Citation Excerpt :
Two assessments were carried out: before injection (PRE) and 1 month post injection (POST). The second assessment was carried out one month post injection because this is when the toxin is at maximal effectiveness (Juzans et al., 1996). A clinical assessment and gait analysis were carried out at each assessment.
In hemiparetic patients, rectus femoris spasticity is one of the main causes of reduced knee flexion in swing phase, known as stiff knee gait. Botulinum toxin is often used to reduce rectus femoris spasticity and to increase knee flexion during swing phase. However, the mechanisms behind these improvements remain poorly understood. The aim of this study was (1) to quantify maximal rectus femoris length and lengthening velocity during gait in ten adult hemiparetic subjects with rectus femoris spasticity and stiff knee gait and to compare these parameters with those of ten healthy subjects and (2) to study the effect of botulinum toxin injection in the rectus femoris muscle on the same parameters.
10 patients with stiff knee gait and rectus femoris spasticity underwent 3D gait analysis before and one month after botulinum toxin injection of the rectus femoris (200 U Botox®, Allergan Inc., Markham, Ontario, CANADA). Rectus femoris length and lengthening velocity were quantified using a musculoskeletal model (SIMM®, MusculoGraphics, Inc., Santa Rosa, California, USA).
Maximal length and lengthening velocity of the rectus femoris were significantly reduced on the paretic side. There was a significant increase in muscle length as well as lengthening velocity during gait following botulinum toxin injection.
This study showed that botulinum toxin injection in the spastic rectus femoris of hemiparetic patients improves muscle kinematics during gait. However maximal rectus femoris length did not reach normal values following injection, suggesting that other mechanisms are likely involved.
Long-term Effects of Repeated Botulinum Toxin Injection in Cosmetic Therapeutics
2022, Annals of Plastic Surgery
Contribution of single-fiber evaluation on monitoring outcomes following injection of botulinum toxin-a: A narrative review of the literature
2021, Toxins
Botulinum toxin type A versus anticholinergics for cervical dystonia
2021, Cochrane Database of Systematic Reviews

View all citing articles on Scopus

View full text

Research paperNerve terminal sprouting in botulinum type-A treated mouse levator auris longus muscle

Abstract

Trends in Cell Biol

Brain Res

Neuroscience

Ophthalmology

Brain Res

Dev Brain Res

Neurosci Lett

Prog Neurobiol

Neuroscience

Neuromusc Disord

J Neurol Sci

Clostridial neurotoxins: handling and action at the cellular and molecular level

Curr Top Microbiol Immunol

Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions

J Physiol (Paris)

Mechanism of action of tetanus and botulinum neurotoxins

Mol Microbiol

Quantal neurotransmitter release and the clostridial neurotoxins' targets

Curr Top Microbiol Immunol

The effects of botulinum toxin on the pattern of innervation of skeletal muscle in the mouse

Quart J Exp Physiol

Properties and use of botulinum toxin and other microbial neurotoxins in medicine

Microbiol Rev

Therapeutic uses of botulinum toxin

New Engl J Med

Research paper
Nerve terminal sprouting in botulinum type-A treated mouse levator auris longus muscle