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PubMed1975

[The structure of muscle spindles in the intercostal muscles and rectus abdominis of the human fetus].

The structure and innervation of muscle fibres were studied in external intercostal muscles and the streight muscle of the abdomen in 24--26-week human fetuses. The diameter of most spindles was shown to be within the range of 50--70 mkm, while in the streight muscle of the abdomen it could reach 100 mkm. In the external intercostal muscles the spindles, as a rule, were longer (300-500 mkm) than in the streight muscle of the abdomen (100--300 mkm) which was likely due to special functioning of the spindles in rhythmically working muscles. According to sensory innervation all the spindles may be divided into 3 main types: simple, intermediate and complex. In the external intercostal muscles there occur 3 types of spindles, while in the streight muscle of the abdomen there are spindles of a complex type.

Humans↗

PubMed1975

Topological distribution of muscle spindles in the human tongue and its significance in proprioception.

In order to obtain numerical data concerning the lingual muscle spindle distribution, the muscle spindles were histologically surveyed on the serial frontal and horizontal sections (stained by hematoxylin-eosin) from the apex to the radix of the tongue. On one side four hundred and sixty-six muscle spindles were counted in seven muscles, the superior longitudinal muscle containing 159 spindles, the genioglossus 80, the transverse 79, the styloglossus 75, the hyoglossus 37, the inferior longitudinal 22 and the vertical 14. The chondroglossus and the palatoglossus are devoid of the spindles. The question of whether the proprioceptive impulses from the lingual spindles lie in the hypoglossus nerve or in the lingual nerve has remained unsolved. This histological confirmation of the pathway and primary cell station of the lingual proprioceptive afferents is the subject in which the authors are greatly interested.

Humans↗

PubMed2003

Induction of C-anaphase and diplochromosome through dysregulation of spindle assembly checkpoint by sodium arsenite in human fibroblasts.

Cytogenetic alterations induced by arsenite are associated with its carcinogenic activity. Cytogenetic analysis revealed first that arsenite induced c-anaphases in a time- and dose-dependent manner in human fibroblasts (HFW). With additional incubation of arsenite-arrested mitotic cells in drug-free medium for 0-48 h, approximately 35% exited from mitosis without cell division. This was confirmed by the appearance of tetraploid metaphase, mainly diplochromosomes, in the subsequent cell division. Treatment of HFW cells with both nocodazole, a known agent of microtubular depolymerization, and Taxol, which induces tubulin polymerization and inhibits disassembly of microtubules, resulted in remarkable mitotic arrest but induced only negligible c-anaphase, tetraploidy, and diplochromosomes. Staurosporine, a kinase inhibitor that could effectively reduce arsenite-induced c-anaphase, could also decrease the development of diplochromosomes in the subsequent cell division cycle. These results imply that arsenite-induced c-anaphases mainly exited from mitosis without cell division and became tetraploid in the subsequent cell cycle. Antitubulin immunofluorescent staining confirmed no formation of bipolar spindles in nocodazole-arrested mitotic HFW cells, whereas in arsenite-arrested mitotic cells bipolar spindles were present but distorted in appearance and apparently dysfunctional. Mitotic arrest deficient 2 (Mad2) signal was, as expected, clearly visible at centromeres of nocodazole-arrested mitotic cells. However, the Mad2 signal at centrosomes became insignificant in either arsenite-arrested or nocodazole/arsenite-arrested mitotic cells. In addition, the association of Mad2 with the APC/C(cdc20) complex and the accumulation of Pds1, an anaphase inhibitor, were remarkably reduced in arsenite-arrested mitotic cells as compared with nocodazole-arrested mitotic cells. These results support the observation that nocodazole can inhibit spindle formation and, hence, activate spindle assembly checkpoint to arrest cells at metaphase. In contrast, the dysfunctional bipolar spindles in arsenite-arrested mitotic cells could not effectively activate spindle assembly checkpoint and, hence, resulted in formation of c-anaphase and diplochromosomes in the subsequent cell division.

Anaphase↗

PubMed2004

[Influence of cryoprotectant and cooling rate in vitrification method on the spindles of rabbit oocytes].

OBJECTIVE: To investigate the influence of cryoprotectants and cooling rates in vitrification method on the spindles of rabbit M II oocytes. METHODS: Rabbit oocytes were verified by using cryoloop with ethylene glycol (EG) singly or EG combined with dimethyl sulphoxide (DMSO) as cryoprotectants, and cooled by taking oocytes directly into liquid nitrogen or by vitrification machine. After frozen rabbit oocytes thawed, the microtubulin and chromosome of the spindles were fixation and stained by immunofluorescent method. Confocal microscope was used to reveal spindle configuration. RESULTS: In the two protocols of single EG used and EG combined with DMSO, the spindles were severely injured. But in protocol of EG combined with DMSO and at ultra-rapid cooling rate, the normal configuration of spindle rate of thawed rabbit oocytes was similar to that of the control group. CONCLUSION: The protocol of EG combined with DMSO as cryoprotectants and with extremely high cooling rate by vitrification machine can produce the best effect on conservation of spindle configuration in vitrification of rabbit oocytes.

Animals↗

PubMed2005

Mitotic spindle checkpoint inactivation by trichostatin a defines a mechanism for increasing cancer cell killing by microtubule-disrupting agents.

Microtubule-disrupting agents such as the taxanes comprise some of the most clinically useful chemotherapeutic agents and invoke the spindle checkpoint in proliferating cells. A robust spindle checkpoint in turn may forestall mitotic catastrophe, potentially providing a mechanism that permits cancer cells to survive transient exposure to these drugs. Previous reports on G2-M cell cycle progression by histone deacetylase inhibitors suggested a potential role in modulating the therapeutic efficacy of microtubule-disrupting agents. As both classes of agents are generally administered in clinical trials as pulse treatments, we investigated in human cancer cells the effects of brief treatments with the histone deacetylase inhibitor trichostatin A (TSA) alone or with nocodazole or paclitaxel (Taxol) on cell cycle progression and the spindle checkpoint. Treatment of synchronized cells with 200 ng/ml of TSA alone for eight hours to completely block class I and II HDACs did not interfere with progression into mitosis with chromosomal condensation as confirmed by MPM-2 expression. TSA treatment at this concentration surprisingly did not interfere with formation of the mitotic spindle or centrosomal separation, but instead led to missegregation of chromosomes, suggesting effects on the spindle checkpoint. Consistent with this hypothesis, TSA abrogated the phosphorylation and kinetochore localization of the mitotic checkpoint protein BubR1 and the phosphorylation of histone H3 after paclitaxel and nocodazole treatment. These effects in turn led to rapid cell death and considerably reduced clonogenic survival. These results together suggest that by inactivating the spindle checkpoint, TSA can potentiate the lethal effects of microtubule-disrupting drugs, a strategy that might be usefully exploited for optimizing anticancer therapy.

Antineoplastic Agents↗

PubMed2005

[Effects of three Chinese traditional drugs on afferent discharge from single muscle spindle in toads].

OBJECTIVE: To shed some light on treatment of muscle atrophy through testing the effects of several Chinese traditional drugs that can invigorate blood circulation on the afferent discharge of muscle spindle. METHOD: Single muscle spindle was isolated from sartorius muscle of toad. Afferent discharge from the muscle spindle was recorded using air-gap technique and effects of three Chinese traditional drugs on afferent activity of the muscle spindle were observed. RESULT: Ligustrazine could markedly tingle the spontaneous electrical activity of the muscle spindle, and it also showed a good dose-response relationship, while Salvia Miltiorrhiza and Safflower had no such excitative effect. CONCLUSION: It is known that ligustrazine can expand blood vessels and agitate microcirculation, and this effect on the muscle spindle makes it helpful for persons with muscle atrophy.

Animals↗

PubMed1979

Muscle spindle supply to the masticatory muscles in the Japane ermine (Carnivora).

Histological examination of the jaw muscles of the Japanese ermine showed that 4 jaw-closing muscles have 13 muscle spindles on one side of the face. The temporal muscle has 99 muscle spindles, 68 being in the anterior vertical and 31 in the posterior horizontal belly. The masseter muscle has 33 muscle spindles, 23 being in the profound and 10 in the superficial belly. The medial pterygoid muscle has 7 muscle spindles and the zygomaticomandibular muscle contains 4 muscle spindles. The lateral pterygoid and the jaw-opening muscles have no spindles.

Animals↗

PubMed2005

Objective measurement of spindle orientation in early Caenorhabditis elegans embryo.

The spindle orientation is a crucial piece of information to understand the development of embryo. The spindle forms during cell division and the cell divides along the spindle axis. Spindle orientation was measured in many different mutant embryos of Caenrohabditis elegans. However, the objectivity and the productivity of these measurements were low because these measurements were made manually. Here we present a system that automates the measurement of the spindle orientation in C. elegans embryo. Automation increases the objectivity and productivity of the measurement. We confirmed the applicability of the system by applying it to spindles during the second divisions in wild-type and mutant C. elegans embryos.

Animals↗

PubMed1991

Fusimotor reflex profiles of individual triceps surae primary muscle spindle afferents assessed with multi-afferent recording technique.

The experiments were performed on 21 cats anaesthetized with alpha-chloralose. The aim of the study was to investigate sets of simultaneously recorded spindle afferents (2-4 in each set) from the triceps surae muscle (GS) with respect to the pattern of fusimotor reflex effects evoked by different types of ipsi- and contralateral reflex stimulation. The afferents' responses to sinusoidal stretching of the GS muscle were determined and the fusimotor reflex effects were assessed by comparing the afferent responses (i.e. the mean rate of firing and the depth of modulation) elicited during reflex stimulation with those evoked in absence of any reflex stimulus. Natural of electrical activations of ipsi- and contralateral muscle, skin and joint receptor afferents were used as reflex stimuli. The spindle afferents were influenced by several modalities and from wide areas, with a majority responding to both ipsi- and contralateral stimuli. A particular reflex stimulus often caused different effects on different afferents, and the various reflex stimuli seldom gave similar effects on a particular afferent. Multivariate analysis revealed that the variation in response profiles among simultaneously recorded afferents were as great as between afferents recorded on different occasions. This suggests that the individualized response prifiles, observed in earlier investigations, represent a very diversified reflex control of the spindle primary afferents, and are not a reflection of changes in the setting of the spinal interneuronal network, occurring during the time interval between the recordings of different units. Also, there was no relation between the conduction velocity of the afferents and the reflex profiles of the afferents, but non-linear relations were found between effects elicited by different types of stimuli. Indications were also found that it may be possible to separate the population of GS muscle spindles into subgroups, according to the fusimotor effects exhibited by activation of various categories of ipsi- and contralateral receptor afferents. It is concluded that one possible way of making the very complex reflex system controlling the muscle spindles intelligible may be a combination of multiple simultaneous recordings of spindle afferents and multivariate analysis.

Afferent Pathways↗

PubMed1978

Position sensitivity of de-efferented muscle spindles in experimental acrylamide neuropathy.

An experimental neuropathy was induced in cats by injections of acrylamide (7.5, 15 or 30 mg/kg/day) for 2 to 10 days. The responses of primary and secondary endings of soleus muscle spindles to stretch were evaluated and correlated with the appearance of ataxia and incoordinated motor movements. Animals that received 15 or 30 mg/kg/day became ataxic and demonstrated poor motor coordination on the 7th or 4th day, respectively. At these times, both primary and secondary endings of muscle spindles had elevated thresholds and diminished discharge frequencies. Continued acrylamide administration resulted in exacerbation of the clinical symptoms and further attenuation of spindle responses. The discontinuation of acrylamide was followed by slow recovery. Only those cats which received a total dose of 75 mg/kg or less remained asymptomatic and had normal spindle function. The coincidence of onset of motor coordination deficits and spindle dysfunction, coupled with a lack of demonstrable motor defect at the same time, suggests that the initial clinical features of acrylamide neuropathy may be partly the consequence of impaired spindle function.

Acrylamides↗

PubMed1986

Effects of nerve growth factor on differentiation of muscle spindles following nerve lesion in neonatal rats.

Central synaptic function of Group Ia sensory fibers has been shown to be enhanced by daily applications of NGF in neonatal rats. In the periphery, Group Ia sensory fibers are known to trigger the differentiation of muscle spindles. In the present study we examined, in neonatal rats, whether daily NGF treatment affects the number or structure of spindles formed in muscle whose nerve has been crushed. The results show that 25-35 d after nerve crush, de novo supernumerary spindles were formed by treatment with NGF in the temporarily denervated muscle. The number of spindles in the corresponding muscle on the contralateral, intact side was not affected by NGF treatment. Following nerve crush alone, the mean number of spindles in the muscle was not significantly different from the normal value. It is suggested that treatment of neonatal rats with NGF may facilitate the outgrowth of excessive peripheral collaterals of regenerating Group Ia sensory fibers, which, in turn, contributes to the formation of de novo spindles as a result of interaction with myotubes.

Animals↗

PubMed1986

Immunofluorescence analysis of sucrose-induced changes in spindle morphology.

Metaphase and anaphase PtK1 cells show spindle elongation without concomitant chromosome motion when treated with culture medium containing 0.5 M sucrose. Electron microscopy has shown sucrose-induced changes in microtubule (MT) organization, changes in trilaminar kinetochore structure, and specific kinetochore-MT associations which may account for these results. In this paper we employ double-label immunofluorescence techniques using antibodies against tubulin and the kinetochore to analyze changes in spindle microtubule and kinetochore distribution produced by sucrose treatment. Cells treated from prometaphase through anaphase with 0.5 M sucrose from 10 min to 2 h showed spindle elongation and a distinct rearrangement of spindle microtubules into bundles, with a pronounced increase in length of interpolar microtubule bundles. In sucrose-treated mitotic cells kinetochores remained as antigenically distinct structures, similar to those found in untreated interphase cells. Kinetochore determinants remained positioned within a diffuse chromatin mass, but the orientation of sister kinetochores to opposite spindle poles was lost. Instead, kinetochore pairs were found in lateral association with microtubule bundles, with several pairs of determinants associated with a single bundle in many instances. Cells released from 0.5 M sucrose treatment showed a return of the spindle to a pretreatment arrangement for both the microtubules and kinetochore determinants.

Anaphase↗

PubMed1980

Number and distribution of muscle spindles in the masticatory muscles of the rat.

The frequency and distribution of muscle spindles in the muscles of mastication of the rat have been studied. The average number of spindles found was 110 in the masseter, 75 in the temporalis and 25 in the medial pterygoid muscle, the spindles being predominantly in the medial parts of these muscles. No muscle spindles were found in the lateral pterygoid or posterior digastric muscle, and only isolated spindles were found in a few of the anterior digastric muscles. These differences between the jaw-closing and the jaw-opening muscles are intriguing and ask for further investigation of the role of the muscle spindles in mastication.

Animals↗

PubMed1980

The number, distribution and density of muscle spindles in two wing muscles of the domestic duck.

A study by serial longitudinal sections of two dorsal wing muscles of the duck, the extensor pollicis and the extensor digitorum communis, has shown that: (1) The extensor pollicis muscle shows a spindle content range of 19--27, mean 23.2, giving a spindle density of 76.7/g; the extensor digitorum communis muscle shows a spindle content range of 37--59, mean 47.6, and a spindle density of 119.0/g. (2) Spindles in the extensor pollicis muscle are randomly distributed, while those in the extensor digitorum muscle are located primarily in the proximal two thirds of the muscle. (3) The present data have been discussed in relation to previous observations of muscle spindles occurring in some avian and mammalian skeletal muscles.

Animals↗

PubMed1984

From proto-mitosis to mitosis--an alternative hypothesis on the origin and evolution of the mitotic spindle.

Based on the assumption that the ancestral proto-eukaryote evolved from an ameboid prokaryote I propose the hypothesis that nuclear division of the proto-eukaryote was effected by the same system of contractile filaments it used for ameboid movement and cytosis . When the nuclear membranes evolved from the cell membrane, contractile filaments remained associated with them. The attachment site of the genome in the nuclear envelope was linked to the cell membrane by specialized contractile filaments. During protomitosis , i.e., nuclear and cell division of the proto-eukaryote, these filaments performed segregation of the chromosomes, whereas others constricted and cleaved the nucleus and the mother cell. When microtubules (MTs) had evolved in the cytoplasm, they also became engaged in nuclear division. Initially, an extranuclear bundle of MTs assisted chromosome segregation by establishing a defined axis. The evoluntionary tendency then was towards an increasingly important role for MTs. Spindle pole bodies ( SPBs ) developed from the chromosomal attachment sites in the nuclear envelope and organized an extranuclear central spindle. The chromosomes remained attached to the SPBs during nuclear division. In a subsequent step the spindle became permanently lodged inside the nucleus. Chromosomes detached from the SPBs and acquired kinetochores and kinetochore-MTs. At first, this spindle segregated chromosomes by elongation, the kinetochore-MTs playing the role of static anchors. Later, spindle elongation was supplemented by poleward movement of the chromosomes. When dissolution of the nuclear envelope at the beginning of mitosis became a permanent feature, the open spindle of higher eukaryotes was born.

Animals↗

PubMed1994

Interspike intervals of secondary muscle spindle and urinary bladder afferents in relation to the oscillation periods of sacral spinal oscillators for continence in man.

Two pairs of wire electrodes were used to record afferent and efferent single fibre extracellular action potentials (APs) from human nerve root filaments. The nerve fibres were identified according to the group to which they belong by comparing the afferent and efferent conduction velocity distribution histograms and identifying peaks and ranges of nerve fibre groups. Secondary muscle spindle afferents and alpha 2-motoneurones (FR) were identified by having the same peak group conduction velocity (calibration relation), which is 50 m/s at 36 degrees C. On the basis of AP wave form comparisons, the natural impulse patterns of five secondary muscle spindle afferents, two fusimotor motoneurones and two oscillatory firing alpha 2-motoneurones could be identified in the dorsal S4 root. The patterns of single endings of secondary spindle afferent fibres could be identified. The shortest interspike intervals of single endings of all secondary muscle spindle afferents had the same duration as the shortest interspike intervals of the two fusimotor fibres (80 ms) and equalled a half of the oscillation period of one repetitively firing alpha 2-motoneurone (6 Hz) probably innervating the external anal sphincter (three AP impulse train firing). In another more rostral dorsal root filament (probably S3 or S2) of the same human, the interspike intervals of six secondary spindle afferents were more variable. The values of peaks in the interspike interval distributions ranged from 60 to 102 ms. In the coccygeal root, the interspike interval duration ranged from 160 to 185 ms, directly contributing to the drive of the oscillatory firing alpha 2-motoneurone. The different agreement between the oscillation period and the interspike intervals of the spindle afferents in different segments indicate that the oscillatory firing CNS circuitry was localized within S3 to S5 segments of the conus medullaris for the drive of the anal sphincter. An alpha 2-motoneurone firing repeatedly with 1 to 2 AP impulse trains, innervating most likely the external urethral sphincter, fired at a frequency of 9.1 to 6.7 Hz, a similar frequency of the oscillation as the interspike intervals from two activated stretch receptors of the urinary bladder wall. The measurements of this brain-dead human indicates that in this case the neuronal circuitry driving the external anal sphincter was mainly confined to the sacral micturition and defecation centre, mainly located in the S3 to S5 segments.

Action Potentials↗

PubMed1993

Impulse patterns of single encoding sites of human secondary muscle spindle afferents.

1. By recording single-fibre action potentials (APs) from human sacral nerve roots, the impulse patterns of 6 secondary spindle afferents could be identified, analysed and compared with the impulse trains of oscillatory firing alpha 2-motoneurons. 2. Secondary spindle afferents fired with single APs, doublets, bursts and equidistant APs. On the assumption that the most simple firing pattern of a single fibre with a shortest interspike interval (II) of 80 msec was generated by a single encoding site, the firing patterns of the other afferents could be splitted into firing patterns of single encoding sites with similar II distributions and also with a shortest II of about 80 msec. 3. Successive IIs also reflected the different ways of firing of the secondary muscle spindle afferents. A fibre from a paraplegic with bladder dyssynergia seemed to show a higher activity than a comparable probably normal fibre. The doublet IIs of two secondary spindle afferents ranged from about 9 to 14 msec with peaks at 10.2, 11.2 and 13 msec in the distributions. Multiple encoder sites increased discharge rates of parent fibres, but did not always regularize the output discharge. 4. The simultaneously plotted impulse patterns of 4 secondary spindle afferents showed coordinated firing: they did not fire simultaneously but regularized the summed activity. A phase of 50 msec (range 30 to 70 msec) often occurred between the spindle afferent APs and the impulse trains of an oscillatory firing alpha 2-motoneuron. An afferent drive of the oscillator with a certain phase is likely.

Action Potentials↗

PubMed1996

Characteristic properties of superficial lumbrical spindles in the cat hind limb, related to their bag1 fibres.

Superficial lumbrical spindles of the cat show several important differences as compared with the classic picture of the spindle, derived principally from tenuissimus. Thus long chain fibres occur in a high proportion of superficial lumbrical spindles, and there is great individual variation in the number of bag fibres present. This study is especially concerned with the morphology and relationships of the bag1, fibre, which are again highly unusual. Most notably, bag1 fibres were almost always the longest intrafusal fibres, typically exceeding bag2 fibres by about 2 mm in total length. They also commonly exhibited the greatest diameter, especially in the extracapsular region where, uniquely, they normally increased in size on leaving the capsule, often becoming similar to extrafusal fibres in this respect. In a few spindles where there was only a single bag fibre this was more often a bag1 than is the case for similar spindles in tenuissimus, and in tandem-linked spindles the continuous bag fibres were more often bag1 than bag2. These results contribute to growing evidence that different muscles exhibit characteristic features of the structure and innervation of their proprioceptors, which may reflect adaptations to local control requirements.

Animals↗