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Sample records for supernumerary mauthner axons

  1. In vivo Imaging of Mitochondrial Transport in Single-Axon Regeneration of Zebrafish Mauthner Cells

    Science.gov (United States)

    Xu, Yang; Chen, Min; Hu, Bingbing; Huang, Rongchen; Hu, Bing

    2017-01-01

    Mitochondrial transport is essential for neuronal function, but the evidence of connections between mitochondrial transport and axon regeneration in the central nervous system (CNS) of living vertebrates remains limited. Here, we developed a novel model to explore mitochondrial transport in a single Mauthner axon (M axon) of zebrafish with non-invasive in vivo imaging. To confirm the feasibility of using this model, we treated labeled zebrafish with nocodazole and demonstrated that it could disrupt mitochondrial transport. We also used two-photon laser axotomy to precisely axotomize M axons and simultaneously recorded their regeneration and the process of mitochondrial transport in living zebrafish larvae. The findings showed that the injured axons with stronger regenerative capability maintain greater mitochondrial motility. Furthermore, to stimulate axon regeneration, treatment with dibutyryl cyclic adenosine monophosphate (db-cAMP) could also augment mitochondrial motility. Taken together, our results provide new evidence that mitochondrial motility is positively correlated with axon regeneration in the living vertebrate CNS. This promising model will be useful for further studies on the interaction between axon regeneration and mitochondrial dynamics, using various genetic and pharmacological techniques. PMID:28174522

  2. Morphometric analysis of Mauthner axon cytoskeletal components in adult and subadult fish.

    Science.gov (United States)

    Alfei, L; Medolago-Albani, L; Zezze, G M; Stefanelli, A

    1992-01-01

    A previous cytoskeletal analysis on trout MA during developmental stages demonstrated, during the subadult stages, neurofilaments (NF) as main components as expressed by the high values of neurofilament to microtubules (MT) ratio which was found to be of the order of 300:1. Since the MA cytoskeletal composition is not known in the adult fish, the MA cytoskeletal composition has been compared to other axons of much smaller diameter of the fasciculus longitudinalis medialis (flm) among which the MA run in the ventral spinal cord. The following parameters were measured on conventional electron microscopy in MA and flm axons cross sections micrographs by means of a computer linked graphic tablet (Apple II): axonal caliber, number of microtubules (MT), microtubular (MT/microns2) and neurofilament (NF/microns2) densities. The analysis of these parameters demonstrated that neurofilaments are the main architectural components in the adult and subadult fish MA and flm axons. However, MA cytoskeletal composition differs from the other flm axons because of its particular very high ratio of neurofilaments to microtubules. The inverse relationship of axonal caliber to microtubular density, previously found in the trout during developmental stages and suggested also for many other vertebrate species, was further confirmed for flm axons which, with calibers 10 times smaller than MA, exhibit a microtubular density 10 times larger.

  3. Visual input controls the functional activity of goldfish Mauthner neuron through the reciprocal synaptic mechanism.

    Science.gov (United States)

    Moshkov, Dmitry A; Shtanchaev, Rashid S; Mikheeva, Irina B; Bezgina, Elena N; Kokanova, Nadezhda A; Mikhailova, Gulnara Z; Tiras, Nadezhda R; Pavlik, Lyubov' L

    2013-03-01

    Goldfish are known to exhibit motor asymmetry due to functional asymmetry of their Mauthner neurons that induce the turns to the right or left during free swimming. It has been previously found that if the less active neuron is subjected to prolonged aimed visual stimulation via its ventral dendrite, the motor asymmetry of goldfish is inverted, testifying that this neuron becomes functionally dominant, while the size of the ventral dendrite under these conditions is reduced 2-3 times compared to its counterpart in mirror neuron. Earlier it has been also revealed that training optokinetic stimulation induces adaptation, a substantial resistance of both fish motor asymmetry and morphofunctional state of Mauthner neurons against prolonged optokinetic stimulation. The aim of this work was to study the cellular mechanisms of the effect of an unusual visual afferent input on goldfish motor asymmetry and Mauthner neuron function in norm and under adaptation. It was shown that serotonin applied onto Mauthner neurons greatly reduces their activity whereas its antagonist ondansetron increases it. Against the background of visual stimulation, serotonin strengthens functional asymmetry between neurons whereas ondansetron smoothes it. Taken together these data suggest the involvement of serotonergic excitatory synaptic transmission in the regulation of Mauthner neurons by vision. Ultrastructural study of the ventral dendrites after prolonged optokinetic stimulation has revealed depletions of numeral axo-axonal synapses with specific morphology, identified by means of immunogold label as serotonergic ones. These latter in turn are situated mainly on shaft boutons, which according to specific ultrastructural features are assigned to axo-dendritic inhibitory synapses. Thus, the excitatory serotonergic synapses seem to affect Mauthner neuron indirectly through inhibitory synapses. Further, it was morphometrically established that adaptation is accompanied by the significant

  4. Origin and function of spiral fibers projecting to the goldfish Mauthner cell.

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    Scott, J W; Zottoli, S J; Beatty, N P; Korn, H

    1994-01-01

    Two neuron types contact the Mauthner cell (M cell) in the axon cap, a specialized region of high electrical resistance surrounding the initial segment of the M cell axon. One type produces a mixed electrical and chemical inhibition of the M cell. The second sends axons into the central core of the axon cap, where they spiral around the initial segment making both conventional synapses and gap junction contacts. The origin and synaptic effects of these spiral fibers have not been studied previously. When goldfish M cells were filled with Lucifer yellow, presynaptic spiral fibers were seen in the axon cap. These fibers could be traced back through the medial longitudinal fasciculus to their somata, near the contralateral fifth nerve motor nucleus. The same somata were labeled by horseradish peroxidase injected extracellularly into the axon cap. Recordings were made in the axon cap and the M cell after stimulation of hindbrain areas near the spiral fiber somata and axons. Extracellularly, a negative potential was observed close to the termination of the spiral fibers and termed the spiral fiber potential (SFP). Intracellularly, a graded, short latency depolarization of the M cell corresponded to the SFP and could cause the M cell to spike. This depolarization did not shunt the membrane, indicating that it may be produced through gap junctions. Intracellular responses to hindbrain stimulation also had a chloride-dependent, second component that shunted the membrane during paired-pulse testing. This inhibitory second component was probably evoked by cells other than the spiral fiber cells themselves.

  5. Dendrite-derived supernumerary axons on adult axotomized motor neurons possess proteins that are essential for the initiation and propagation of action potentials and synaptic vesicle release

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; MacDermid, Victoria E; Montague, Steven J

    2011-01-01

    on these processes matches the arrangement of these channels that is necessary for the initiation and conduction of action potentials. At terminal bouton-like structures they possess key proteins necessary for the release of synaptic vesicles (SV2 and synaptophysin). Thus, axon-like processes emanating from the tips......Axotomy can trigger profound alterations in the neuronal polarity of adult neurons in vivo. This can manifest itself in the development of new axon-like processes emanating from the tips of distal dendrites. Previously, these processes have been defined as axonal based on their axonal morphology....... This study extends this definition to determine whether, more importantly, these processes possess the prerequisite molecular machinery to function as axons. Using a combination of intracellular labeling and immunohistochemistry, we demonstrate that the distribution of voltage-gated sodium channels...

  6. Effect of the pesticide Deltamethrin on the Mauthner cells of Lake Balaton fish.

    Science.gov (United States)

    Csillik, B; Fazakas, J; Nemcsók, J; Knyihár-Csillik, E

    2000-06-01

    Deltamethrin, a synthetic pesticide [(S)alpha-cyano-3-phenoxybenzyl-(1R)-cis-3-(2.2-dibromovinyl)-2,2-dim ethylcyclopropane-carboxylate] used for extermination of mosquitoes on the shores of lake Balaton, has been found to induce severe impairments of the nervous system of several Lake Balaton fish, such as carp (Cyprinus carpio), goldfish (Carassius auratus gibelis Bloch), eel (Anguilla anguilla) and wels (Silurus glanis). It has been shown that Deltamethrin, in a concentration of 1 microgram/liter in the aquarium water, inhibits acetylcholinesterase enzyme activity of the giant Mauthner's nerve cells as well as of the axon terminals synapsing with these cells. Even more importantly, however, Deltamethrin in a concentration of 10 micrograms per liter, induces blockade of the expression of choline acetyltransferase in the bulbous axon terminals synapsing with the lateral dendrites of the Mauthner cells. Since, under normal conditions, the function of the Mauthner cells is to co-ordinate the C-start reaction, by which fish rapidly leave sites of nociceptive stimulation, it stands for reason to assume that Deltamethrin intoxicated fish may be prone to become victims of various factors which endanger survival of the individual. During the last decade, waves of fish deaths were observed in Lake Balaton, which is the largest fresh-water lake in Europe. Fish death coincided with airborne mosquito-killing campaigns. Results of the enzyme- and immunohistochemical studies described in this paper, together with the deleterious effects of Deltamethrin to the enteric nervous system of fish which has been reported earlier (Lang et al., 1997) suggest that fish death might be caused by the indiscriminate use of Deltamethrin airborne spray in the mosquito-extermination campaigns.

  7. Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses

    Science.gov (United States)

    Tabor, Kathryn M.; Bergeron, Sadie A.; Horstick, Eric J.; Jordan, Diana C.; Aho, Vilma; Porkka-Heiskanen, Tarja; Haspel, Gal

    2014-01-01

    Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish. PMID:24848468

  8. Management of supernumerary teeth

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    Abhishek Parolia

    2011-01-01

    Full Text Available Supernumerary paramolars are the rare anomalies of the maxillofacial complex. These are more common in the maxilla than in the mandible. This article reviews the etiology, frequency, classification, complications, diagnosis and management of supernumerary teeth (bilateral maxillary paramolars

  9. Intracranial supernumerary tooth

    Energy Technology Data Exchange (ETDEWEB)

    Sjoeberg, S.; Loerinc, P.

    1984-12-01

    Case report of an accidentally diagnosed supernumerary tooth in the superior orbital fissure. Computed tomography (CT) contributed with a more precise localization of the tooth being situated between the orbit and the brain. CT also showed that there was no cyst or other pathological process around the supernumerary tooth, which is plausible and frequently reported in the literature.

  10. Supernumerary teeth in clinical practice

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    Anna K. Szkaradkiewicz

    2011-07-01

    Full Text Available Introduction: Hyperdontia is the condition of having supernumerary teeth, or teeth which appear in addition to the regular number of teeth. The prevalence rates of supernumerary teeth in the permanent dentition amounts 0.1-6.9%, and in deciduous dentition 0.4-0.8%. The presence of supernumerary teeth can be found in everyday dental practice.Case presentation: We describe 3 cases of patients with supernumerary teeth. First patient had supernumerary lateral incisor 12s, second - premolar fused, multicuspid, supernumerary deciduous tooth 64s of having several interconnected roots, and third - erupted odontoma between teeth 13 and 14. In all cases treatment involved the removal of the supernumerary tooth.Conclusions: The decision on proceeding with the supernumerary teeth should be based on the full clinical picture and interview. Early diagnosis and removal of supernumerary teeth allow to avoid or reduce possible complications.

  11. Supernumerary Teeth in Nepalese Children

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    Varun Pratap Singh

    2014-01-01

    Full Text Available Objective. The objectives of the present study were to investigate the prevalence and characteristics of supernumerary teeth in a patient sample of Nepalese children. Study Design. A survey was performed on 2684 patients (1829 females and 1035 males ranging in age from 6 to 14 for the presence of supernumerary teeth. For each patient with supernumerary teeth the demographic variables (age and sex, number, location, eruption status, and morphology were recorded. Descriptive statistics were performed. Results. Supernumerary teeth were detected in 46 subjects (1.6%, of which 26 were males and 20 were females with a male : female ratio of 1.3 : 1. The most commonly found supernumerary tooth was mesiodens followed by maxillary premolars, maxillary lateral incisor, and mandibular lateral incisor. Of the 55 supernumerary teeth examined, 58.18% (n=32 had conical morphology, followed by tuberculate (30.90%, n=17 and supplemental (10.90%, n=6 forms. The majority of the supernumerary teeth were erupted (56.36%, n=31. Conclusion. The prevalence of supernumerary teeth in Nepalese children was found to be 1.6%, the most frequent type being mesiodens. Conical morphology was found to be the most common form of supernumerary tooth.

  12. Supernumerary teeth in Nepalese children.

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    Singh, Varun Pratap; Sharma, Amita; Sharma, Sonam

    2014-01-01

    The objectives of the present study were to investigate the prevalence and characteristics of supernumerary teeth in a patient sample of Nepalese children. A survey was performed on 2684 patients (1829 females and 1035 males) ranging in age from 6 to 14 for the presence of supernumerary teeth. For each patient with supernumerary teeth the demographic variables (age and sex), number, location, eruption status, and morphology were recorded. Descriptive statistics were performed. Supernumerary teeth were detected in 46 subjects (1.6%), of which 26 were males and 20 were females with a male : female ratio of 1.3 : 1. The most commonly found supernumerary tooth was mesiodens followed by maxillary premolars, maxillary lateral incisor, and mandibular lateral incisor. Of the 55 supernumerary teeth examined, 58.18% (n = 32) had conical morphology, followed by tuberculate (30.90%, n = 17) and supplemental (10.90%, n = 6) forms. The majority of the supernumerary teeth were erupted (56.36%, n = 31). The prevalence of supernumerary teeth in Nepalese children was found to be 1.6%, the most frequent type being mesiodens. Conical morphology was found to be the most common form of supernumerary tooth.

  13. A convergent and essential interneuron pathway for Mauthner-cell-mediated escapes.

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    Lacoste, Alix M B; Schoppik, David; Robson, Drew N; Haesemeyer, Martin; Portugues, Ruben; Li, Jennifer M; Randlett, Owen; Wee, Caroline L; Engert, Florian; Schier, Alexander F

    2015-06-01

    The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits.

  14. Supernumerary Jawbone Tooth: Clinical Case

    OpenAIRE

    Rivas Gutiérrez, Jesús; Carlos Sánchez, María Dolores

    2016-01-01

    Introduction: supernumerary teeth are dental development anomalies, alsoknown as hyperdontia or extra teeth. Their prevalence ranges between 0.3% and 3.8%.Their morphology may be normal or dismorphic and are associated to the etiology ofocclusal alterations. It is important to make an early diagnostic through a radiographicalstudy. Case presentation:this article presents a clinical case of a supernumerary tooth thatcaused rotation and crowding of the anterior bottom teeth, which was addressed...

  15. Supernumerary teeth "mesiodens". Case report.

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    Itro, A; Difalco, P

    2003-09-01

    The supernumerary tooth is an anomaly of dental eruption that is not rare to find in the clinical practice. Among the supernumerary teeth the "mesiodens" is most frequent. The mesiodens is found in the region of the superior central incisors and it can be the cause of many complications. The aim of this work is the description of a rare symptomatic case of mesiodens and the diagnostic and therapeutic strategies to adopt when this dental anomaly occurs. In particular the authors suggest making radiographic examinations only in the family of patients with dental anomalies of number, thinking that the incidence of such anomalies is too low to justify mass radiographic examinations.

  16. Late Developing Supernumeraries in a Case of Nonsyndromic Multiple Supernumerary Teeth

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    Mine Bozkurt

    2015-01-01

    Full Text Available Objective. This case report presents 3-year follow-up of a case of nonsyndromic multiple supernumerary teeth (NSMST with 11 supernumerary teeth, 2 of which showed subsequent formation. Case Report. A 10-year-old girl was referred to the dental clinic with the chief complaint of delayed eruption. Radiographic examination showed 9 retained supernumerary teeth. The treatment plan consisted of extraction of the supernumerary teeth and associated primary teeth in order to allow the permanent teeth to erupt. After 2 years of follow-up, 2 additional supernumerary teeth were observed. Conclusion. Regular follow-up for late forming supernumeraries is crucial for NSMST cases.

  17. Supernumerary teeth in non-syndromic patients

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    Mali, Santosh; Karjodkar, Freny Rashmiraj; Sontakke, Subodh; Sansare, Kaustubh [Nair Hospital Dental College, Maharashtra (India)

    2012-03-15

    Hyperdontia or supernumerary teeth without associated syndrome is a rare phenomenon, as supernumerary teeth are usually associated with cleft lip and palate or other syndromes such as Gardner's syndrome, cleidocranial dysplasia, and so on. Five patients with supernumerary teeth visited our department. They had no familial history or other pathology, certain treatment protocols was modified due to the presence of supernumerary teeth. Non-syndromic supernumerary teeth, if asymptomatic, need to have periodical radiographic observation. If they showed no variation as they impacted in the jaw, careful examination is necessary because they may develop into pathological status such as dentigerous cysts. The importance of a precise clinical history and radiographic examination for patients with multiple supernumerary teeth should be emphasized.

  18. Late Developing Supernumeraries in a Case of Nonsyndromic Multiple Supernumerary Teeth

    OpenAIRE

    Mine Bozkurt; Tugba Bezgin; Ayşegül Tüzüner Öncül; Rukiye Göçer; Şaziye Sarı

    2015-01-01

    Objective. This case report presents 3-year follow-up of a case of nonsyndromic multiple supernumerary teeth (NSMST) with 11 supernumerary teeth, 2 of which showed subsequent formation. Case Report. A 10-year-old girl was referred to the dental clinic with the chief complaint of delayed eruption. Radiographic examination showed 9 retained supernumerary teeth. The treatment plan consisted of extraction of the supernumerary teeth and associated primary teeth in order to allow the permanent tee...

  19. Fibroadenoma in axillary supernumerary breast: case report

    OpenAIRE

    Délio Marques Conde; Renato Zocchio Torresan; Eiji Kashimoto; Luiz Eduardo Campos de Carvalho; Cássio Cardoso Filho

    2005-01-01

    CONTEXT: Supernumerary breast tissue may be affected by the same diseases and alterations that compromise topical breast tissue. Nevertheless, reports of fibroadenoma in supernumerary breast tissue in the axillae are rare. OBJECTIVE: To describe a case of fibroadenoma in an axillary supernumerary breast. DESIGN: Case report. CASE REPORT: A 39-year-old woman was referred to the gynecology and obstetrics outpatient clinic at Hospital Estadual Sumaré, complaining of bilateral axillary masses. Th...

  20. Fibroadenoma in axillary supernumerary breast: case report

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    Délio Marques Conde

    Full Text Available CONTEXT: Supernumerary breast tissue may be affected by the same diseases and alterations that compromise topical breast tissue. Nevertheless, reports of fibroadenoma in supernumerary breast tissue in the axillae are rare. OBJECTIVE: To describe a case of fibroadenoma in an axillary supernumerary breast. DESIGN: Case report. CASE REPORT: A 39-year-old woman was referred to the gynecology and obstetrics outpatient clinic at Hospital Estadual Sumaré, complaining of bilateral axillary masses. The patient reported cosmetic problems and local pain and discomfort. On physical examination, alterations compatible with bilateral axillary accessory breasts, without palpable nodules, were observed. Supplementary examinations (mammography and ultrasonography revealed a 1.1 cm mass in the right axillary breast. The patient underwent resection of the supernumerary breasts and histopathological examination revealed fibroadenoma of the right axillary breast tissue.

  1. Opioids potentiate electrical transmission at mixed synapses on the Mauthner cell.

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    Cachope, Roger; Pereda, Alberto E

    2015-07-01

    Opioid receptors were shown to modulate a variety of cellular processes in the vertebrate central nervous system, including synaptic transmission. While the effects of opioid receptors on chemically mediated transmission have been extensively investigated, little is known of their actions on gap junction-mediated electrical synapses. Here we report that pharmacological activation of mu-opioid receptors led to a long-term enhancement of electrical (and glutamatergic) transmission at identifiable mixed synapses on the goldfish Mauthner cells. The effect also required activation of both dopamine D1/5 receptors and postsynaptic cAMP-dependent protein kinase A, suggesting that opioid-evoked actions are mediated indirectly via the release of dopamine from varicosities known to be located in the vicinity of the synaptic contacts. Moreover, inhibitory inputs situated in the immediate vicinity of these excitatory synapses on the lateral dendrite of the Mauthner cell were not affected by activation of mu-opioid receptors, indicating that their actions are restricted to electrical and glutamatergic transmissions co-existing at mixed contacts. Thus, as their chemical counterparts, electrical synapses can be a target for the modulatory actions of the opioid system. Because gap junctions at these mixed synapses are formed by fish homologs of the neuronal connexin 36, which is widespread in mammalian brain, it is likely that this regulatory property applies to electrical synapses elsewhere as well.

  2. The management of premolar supernumeraries in three orthodontic cases.

    LENUS (Irish Health Repository)

    McNamara, C M

    1997-01-01

    This paper reviews the incidence, etiology and location of supernumerary teeth with emphasis on premolar supernumeraries and examines the management of supernumerary premolars of three patients undergoing orthodontics. These cases demonstrate that the management of premolars is assessed individually and treatments based on potential complications, which may occur during the orthodontic and surgical management of the dentition. Progress and posttreatment radiographs are recommended for the assessment of late forming supernumerary teeth.

  3. Prevalence, etiology, diagnosis, treatment and complications of supernumerary teeth

    OpenAIRE

    Ata-Ali Mahmud, Fadi; Ata-Ali Mahmud, Francisco Javier; Peñarrocha Oltra, David; Peñarrocha Diago, Miguel

    2014-01-01

    The aim of this article was to review the literature on supernumerary teeth, analyzing their prevalence, etiology, diagnosis, treatment and possible complications. An electronic search was made in the Pubmed-Medline database up to January 2014 using the key search terms “multiple supernumerary teeth” (n=279), “prevalence supernumerary teeth” (n=361), and “supernumerary teeth” (n=2412). In addition to the articles initially identified, others were included in the review proceeding from a manua...

  4. Dynamics of electrical transmission at club endings on the Mauthner cells.

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    Pereda, Alberto E; Rash, John E; Nagy, James I; Bennett, Michael V L

    2004-12-01

    Identifiable mixed electrical and chemical synapses on Mauthner cells, the club endings, have historically provided a window for the study of electrical transmission in vertebrates because of their accessibility for both physiological and ultrastructural characterization. Recent data show that electrical transmission at these terminals is mediated by connexin35 (Cx35), the fish ortholog of the mammalian neuronal gap junction protein, connexin36 (Cx36). While electrical synapses are still perceived by many as passive intercellular channels that lack modifiability, a wealth of experimental evidence shows that electrical synapses at club endings are very plastic and subject to dynamic regulatory control by several mechanisms. The widespread distribution of connexin35 and connexin36 and the ubiquity of some of the proposed regulatory elements suggest that other electrical synapses may be similarly regulated.

  5. Supernumerary teeth: Report of four unusual cases

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    Arun Kumar

    2012-01-01

    Full Text Available Supernumerary tooth denotes duplication of tooth in the normal series. It is a developmental anomaly and has been argued to arise from multiple etiologies. These teeth may remain embedded in the alveolar bone or can erupt into the oral cavity. The supernumerary tooth might cause esthetic and/or functional problems, especially if it is situated in the maxillary anterior region. Complications reported were delayed or prevented eruption of succedaneous teeth, displacement or rotation, crowding of the affected region, abnormal diastema, dilacerations, cystic formation, and sometime eruption into the nasal cavity. In this case report, four unusual cases of supernumerary teeth that resulted in varying degrees of disturbances in permanent dentition are presented. Conservative surgical intervention and light orthodontic forces were used to bring the teeth into normal position with minimal disturbance to the surrounding oral structures.

  6. Supernumerary teeth: Report of four unusual cases.

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    Kumar, Arun; Namdev, Ritu; Bakshi, Lokesh; Dutta, Samir

    2012-04-01

    Supernumerary tooth denotes duplication of tooth in the normal series. It is a developmental anomaly and has been argued to arise from multiple etiologies. These teeth may remain embedded in the alveolar bone or can erupt into the oral cavity. The supernumerary tooth might cause esthetic and/or functional problems, especially if it is situated in the maxillary anterior region. Complications reported were delayed or prevented eruption of succedaneous teeth, displacement or rotation, crowding of the affected region, abnormal diastema, dilacerations, cystic formation, and sometime eruption into the nasal cavity. In this case report, four unusual cases of supernumerary teeth that resulted in varying degrees of disturbances in permanent dentition are presented. Conservative surgical intervention and light orthodontic forces were used to bring the teeth into normal position with minimal disturbance to the surrounding oral structures.

  7. Laparoscopic management of tumor in supernumerary ovary

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    Prakash, Ved; Kant, Anita; Parashar, Abha; Rani, Uma

    2016-01-01

    Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities. PMID:27134478

  8. Laparoscopic management of tumor in supernumerary ovary

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    Ved Prakash

    2016-01-01

    Full Text Available Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities.

  9. Ear manipulations reveal a critical period for survival and dendritic development at the single-cell level in Mauthner neurons.

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    Elliott, Karen L; Houston, Douglas W; DeCook, Rhonda; Fritzsch, Bernd

    2015-12-01

    Second-order sensory neurons are dependent on afferents from the sense organs during a critical period in development for their survival and differentiation. Past research has mostly focused on whole populations of neurons, hampering progress in understanding the mechanisms underlying these critical phases. To move toward a better understanding of the molecular and cellular basis of afferent-dependent neuronal development, we developed a new model to study the effects of ear removal on a single identifiable cell in the hindbrain of a frog, the Mauthner cell. Ear extirpation at various stages of Xenopus laevis development defines a critical period of progressively-reduced dependency of Mauthner cell survival/differentiation on the ear afferents. Furthermore, ear removal results in a progressively decreased reduction in the number of dendritic branches. Conversely, addition of an ear results in an increase in the number of dendritic branches. These results suggest that the duration of innervation and the number of inner ear afferents play a quantitative role in Mauthner cell survival/differentiation, including dendritic development.

  10. Supernumerary Teeth in Indian Children: A Survey of 300 Cases

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    Amita Sharma

    2012-01-01

    Full Text Available The aim of this investigation was to study children with supernumerary teeth who visited the Department of Pedodontics and Preventive Dentistry, Government Dental College and Hospital, Rohtak, Haryana, India. Only children with supernumerary teeth were included in the study while patients having supernumerary teeth with associated syndromes were excluded. Supernumeraries were detected by clinical and radiographic examination. The results indicated that males were affected more than females with a sex ratio of 2.9 : 1. Single supernumerary tooth was seen in 79% of the patients, 20% had double, and 1% had three or more supernumeraries. Premaxillary supernumeraries accounted for 93.8% of the cases. Conical shaped supernumerary teeth were the most common type (59.7%. Majority of supernumeraries remained unerupted (65%. Fusion of supernumerary tooth with a regular tooth was observed in 4% of the patients. Talon cusp, an associated dental anomaly, was seen in 5% of the cases. Simultaneous hypodontia occurred in 2.3% of patients with supernumeraries.

  11. Non-syndromic supernumerary teeth: report of a case with 6 supernumerary teeth

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    Taghibakhsh M

    2011-02-01

    Full Text Available "nBackground and Aims: Multiple supernumerary teeth are rare and often found in association with syndromes such as Gardner, Cleidocranial dysplasia and cleft lip and palate, with a much less chance for isolated"nnon-syndromic cases. The aim of this study was to report a case with 6 supernumerary teeth without syndromic association."nCase Report: The patient was a 33 year-old female, referred to oral diseases and diagnosis department with chief complaint of sensitivity to cold and hot food in right upper premolar region. Oral examination revealed 5 erupted lingually supernumerary teeth (four in mandibular and one in maxillary premolar region, respectively. Further panoramic radiography clarified an extra impacted tooth in the palatal region of left premolar maxillary area. All extra teeth had been appeared since the age of 17 during one year, as the patient claimed. Medical history and thorough clinical and paraclinical examinations were not significant except for the hypothyroidism, since 5 years ago. No other family member noticed to be the case. Based on our findings, a diagnosis of non-syndromic multiple supernumerary teeth was established."nConclusion: A thorough examination of each patient presented with supernumerary teeth, including panoramic and intraoral radiographic images may provide valuable information regarding accompanying syndromes and unerupted teeth. Early diagnosis is an essential step for orthodontic or surgical decisions making, preventing or avoiding worsening complications such as malocclusion, adjacent normal teeth delayed eruption or rotation, diasthema, cystic lesions and resorption of contiguous teeth.

  12. Canaliculitis in supernumerary puncta and canaliculi

    Directory of Open Access Journals (Sweden)

    Ku Chui Yong

    2011-08-01

    Full Text Available We report the first case of supernumerary puncta and canaliculi presented with canaliculitis. A-59 year-old gentleman presented with painful swelling of the left lower lid for a week, which was associated with epiphora. The swelling was confined to the nasal aspect of the left lower lid (0.5¥0.5 mm with inflamed overlying skin. Two puncta (0.5 mm apart were noted. The outer punctum at the normal anatomical position was a cul-de-sac while the inner punctum it the caruncle was patent. We described the embryology leading to supernumerary puncta and canaliculi to explain the paradoxical patency of the abnormally located punctum as well as the pathomechanism leading to canaliculitis. The patient was treated with oral cloxacillin 500 mg, 6 hourly for 5 days; the cellulitis subsided after three days.

  13. Supernumerary teeth: Review of literature and decision support system

    Directory of Open Access Journals (Sweden)

    Deepti Amarlal

    2013-01-01

    Full Text Available Supernumerary teeth are those which are additional or in excess of the normal number. They can be either single or multiple, unilateral or bilateral and can be present anywhere in the dental arch with predilection for the premaxilla. Supernumerary teeth are mostly classified on position and form. Timing of surgical intervention of supernumerary teeth has been controversial with various authors having different opinions. Hence a new decision support system is put forward which can help in the treatment planning of supernumerary teeth.

  14. The effects of impacted premaxillary supernumerary teeth on permanent incisors

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yun Hoa; Kim, Ji Yeon; Cho, Bong Hae [School of Dentistry, Pusan National University, Yangsan (Korea, Republic of)

    2016-12-15

    The aim of this study was to examine the radiographic features associated with impacted premaxillary supernumerary teeth, to determine the relationship between their characteristics and their effects on permanent incisors, and to investigate the types of orthodontic treatment that patients received after the extraction of impacted supernumerary teeth. The clinical records and radiographs of 193 patients whose impacted premaxillary supernumerary teeth were removed were retrospectively reviewed, and 241 impacted supernumerary teeth were examined. Cone-beam computed tomographic images and panoramic radiographs were examined to determine the number, location, sagittal position, orientation, and morphology of the supernumerary teeth. Their effects on permanent incisors and the orthodontic treatment received by patients after the extraction of the supernumeraries were also investigated. Supernumerary teeth were most frequently observed in the central incisor region, in the palatal position, in the inverted orientation, and were most commonly conical in shape. The most common complication was median diastema, followed by displacement and delayed eruption of the adjacent incisors. Ten (71.4%) of the 14 odontomas showed delayed eruption of the adjacent incisors. Displacement of the incisors was more frequently observed in association with supernumerary teeth with tuberculate or supplemental shapes. Orthodontic traction was most frequently performed after the removal of odontomas. In 32 cases (13.3%), permanent incisors erupted after the orthodontic creation of sufficient space. Median diastema was most common complication. The delayed eruption of incisors was common in supernumerary teeth with a vertical orientation and an odontoma shape.

  15. The effects of impacted premaxillary supernumerary teeth on permanent incisors

    Science.gov (United States)

    Jung, Yun-Hoa; Kim, Ji-Yeon

    2016-01-01

    Purpose The aim of this study was to examine the radiographic features associated with impacted premaxillary supernumerary teeth, to determine the relationship between their characteristics and their effects on permanent incisors, and to investigate the types of orthodontic treatment that patients received after the extraction of impacted supernumerary teeth. Materials and Methods The clinical records and radiographs of 193 patients whose impacted premaxillary supernumerary teeth were removed were retrospectively reviewed, and 241 impacted supernumerary teeth were examined. Cone-beam computed tomographic images and panoramic radiographs were examined to determine the number, location, sagittal position, orientation, and morphology of the supernumerary teeth. Their effects on permanent incisors and the orthodontic treatment received by patients after the extraction of the supernumeraries were also investigated. Results Supernumerary teeth were most frequently observed in the central incisor region, in the palatal position, in the inverted orientation, and were most commonly conical in shape. The most common complication was median diastema, followed by displacement and delayed eruption of the adjacent incisors. Ten (71.4%) of the 14 odontomas showed delayed eruption of the adjacent incisors. Displacement of the incisors was more frequently observed in association with supernumerary teeth with tuberculate or supplemental shapes. Orthodontic traction was most frequently performed after the removal of odontomas. In 32 cases (13.3%), permanent incisors erupted after the orthodontic creation of sufficient space. Conclusion Median diastema was most common complication. The delayed eruption of incisors was common in supernumerary teeth with a vertical orientation and an odontoma shape. PMID:28035303

  16. Bilateral supernumerary teeth in deciduous dentition-a rarity.

    Science.gov (United States)

    Acharya, Sonu; Ghosh, Chiranjit; Mondal, Pradeep Kumar

    2014-05-01

    Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stages. They are of great concern to the dentists and parents because of the eruption, occlusal, and esthetic problems they can cause. Supernumerary teeth occur more frequently in the permanent dentition but rarely in primary dentition and more often seen in males. A supernumerary tooth in the primary dentition can cause ectopic or delayed eruption of permanent central incisors which will further alter occlusion and may compromise esthetics and formation of dentigerous cysts. Here we discuss a case of bilateral supernumerary teeth in deciduous dentition in a female child.

  17. NMDA receptors on zebrafish Mauthner cells require CaMKII-α for normal development.

    Science.gov (United States)

    Roy, Birbickram; Ferdous, Jannatul; Ali, Declan W

    2015-02-01

    Calcium/calmodulin dependent protein kinase 2 (CaMKII) is a multifunctional protein that is highly enriched in the synapse. It plays important roles in neuronal functions such as synaptic plasticity, synaptogenesis, and neural development. Gene duplication in zebrafish has resulted in the occurrence of seven CaMKII genes (camk2a, camk2b1, camk2b2, camk2g1, camk2g2, camk2d1, and camk2d2) that are developmentally expressed. In this study, we used single cell, real-time quantitative PCR to investigate the expression of CaMKII genes in individual Mauthner cells (M-cells) of 2 days post fertilization (dpf) zebrafish embryos. We found that out of seven different CaMKII genes, only the mRNA for CaMKII-α was expressed in the M-cell at detectable levels, while all other isoforms were undetectable. Morpholino knockdown of CaMKII-α had no significant effect on AMPA synaptic currents (mEPSCs) but decreased the amplitude of NMDA mEPSCs. NMDA events exhibited a biexponential decay with τfast ≈ 30 ms and τslow ≈ 300 ms. Knockdown of CaMKII-α specifically reduced the amplitude of the slow component of the NMDA-mediated currents (mEPSCs), without affecting the fast component, the frequency, or the kinetics of the mEPSCs. Immunolabelling of the M-cell showed increased dendritic arborizations in the morphants compared with controls, and knockdown of CaMKII-α altered locomotor behaviors of touch responses. These results suggest that CaMKII-α is present in embryonic M-cells and that it plays a role in the normal development of excitatory synapses. Our findings pave the way for determining the function of specific CaMKII isoforms during the early stages of M-cell development.

  18. β-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner.

    Science.gov (United States)

    Banote, Rakesh Kumar; Edling, Malin; Eliassen, Fredrik; Kettunen, Petronella; Zetterberg, Henrik; Abramsson, Alexandra

    2016-05-01

    Amyloid precursor protein (APP) is a transmembrane glycoprotein that has been the subject of intense research because of its implication in Alzheimer's disease. However, the physiological function of APP in the development and maintenance of the central nervous system remains largely unknown. We have previously shown that the APP homologue in zebrafish (Danio rerio), Appb, is required for motor neuron patterning and formation. Here we study the function of Appb during neurogenesis in the zebrafish hindbrain. Partial knockdown of Appb using antisense morpholino oligonucleotides blocked the formation of the Mauthner neurons, uni- or bilaterally, with an aberrant behavior as a consequence of this cellular change. The Appb morphants had decreased neurogenesis, increased notch signaling and notch1a expression at the expense of deltaA/D expression. The Mauthner cell development could be restored either by a general decrease in Notch signaling through γ-secretase inhibition or by a partial knock down of Notch1a. Together, this demonstrates the importance of Appb in neurogenesis and for the first time shows the essential requirement of Appb in the formation of a specific cell type, the Mauthner cell, in the hindbrain during development. Our results suggest that Appb-regulated neurogenesis is mediated through balancing the Notch1a signaling pathway and provide new insights into the development of the Mauthner cell.

  19. Impacted supernumerary tooth in coronoid process: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Won Se; Lee, Je Ho; Park, Hyok; Jung, Ho Gul; Kim, Kee Deog [Yonsei University College of Dentistry, Seoul (Korea, Republic of)

    2010-06-15

    Impaction of tooth is a situation in which an unerupted tooth is wedged against another tooth or teeth or otherwise located so that it cannot erupt normally. The supernumerary tooth is also called as hyperdontia and defined as the condition of having additional tooth to the regular number of teeth. The most common supernumerary tooth is a mesiodens, which is a mal-formed, peg-like tooth that occurs between the maxillary incisors. The supernumerary tooth is commonly impacted but they are frequently impacted on maxilla. Ectopic impaction of supernumerary tooth on mandibular condyle, coronoid process, ascending ramus, and pterygomandibular space is very rare condition. In this case, we report a case of impacted supernumerary tooth on mandibular sigmoid notch without definite pathologic change.

  20. Bilaterally impacted mandibular supernumerary premolars associated with unusual clinical complications

    Directory of Open Access Journals (Sweden)

    Zameer Pasha

    2013-01-01

    Full Text Available Supernumerary teeth are extra teeth in comparison to the normal dentition. Their prevalence varies between 0.1% and 3.8%. Supernumeraries are more common in permanent dentition and its incidence is higher in maxillary incisor region, followed by maxillary third molar and mandibular molar, premolar, canine, and lateral incisor. The prevalence of supernumerary premolars is between 0.075-0.26%, and they may occur in single or multiple numbers Bilateral occurrence is uncommon and large percentage of supernumerary premolars remains impacted, unerupted, and usually asymptomatic; radiograph plays an important role in diagnosis of these. The present paper reports a case of bilaterally impacted completely developed supernumerary premolars associated with common clinical complication in unusual manner along with taurodontism of the upper and lower molars.

  1. Multilobed mesiodens: a supernumerary tooth with unusual morphology.

    Science.gov (United States)

    Dave, Bhavna; Patel, Jalark; Swadas, Milan; Mallikarjuna, Rachappa

    2013-02-06

    An 8-year-old boy came with a chief complaint of an abnormally shaped tooth situated in upper front teeth region. On examination a supernumerary tooth with multiple lobes was present palatally to the maxillary right permanent central incisor. The morphology of the tooth crown was found to be unusual due to the presence of five lobes in the crown portion. Because of the supernumerary tooth, the permanent right central incisor was displaced labially. Radiographic examination showed a completely formed supernumerary tooth with dilacerated root. On the basis of clinical and radiographic examination, the supernumerary tooth was diagnosed as multilobed mesiodens. Since patient expressed dissatisfaction with the presence of supernumerary tooth, it was decided to extract this mesiodens followed by orthodontic treatment for alignment of labially placed maxillary right permanent central incisor.

  2. Supernumerary and supplemental teeth: case report.

    Science.gov (United States)

    Lo Giudice, G; Nigrone, V; Longo, A; Cicciù, M

    2008-06-01

    This is to report the case of a ten year old child affected by a numeric dental anomaly showing the pathologic condition characterised by the simultaneous presence of supernumerary and supplemental teeth. The anomaly was analysed to plan the best surgical and orthodontic treatments. Dental history, clinical and instrumental examinations were made to perform a correct orthodontic examination and diagnosis. A young patient was affected by numeric dental anomaly in the upper jaw. We observed a high number of teeth, specifically two normally formed supplemental lateral permanent incisors and an unerupted mesiodens placed between the upper central incisors. Firstly, the supplemental lateral teeth were extracted. This surgical therapy and the application of a space maintainer were made to permit the eruption of the permanent canines. Then the mesiodens also underwent surgical treatment (i.e. extraction). Eventually, physiologic eruption of permanent teeth was allowed by the planned surgical-orthodontic treatment. Aim of the surgical-orthodontic treatment was extraction of the unerupted supernumerary teeth to obtain the physiologic eruption of the permanent ones. Orthodontic treatment is important to solve malocclusions and maintaining the space for the eruption of permanent teeth. Aesthetics and function are two important parameters in modern dentistry. All clinicians should try to make a correct and rational diagnosis for both simple and complex dental pathologies. Particularly in young children, invasive and surgical disinclusive techniques can be substituted by interceptive orthodontic treatments.

  3. Graphene with vacancies: Supernumerary zero modes

    Science.gov (United States)

    Weik, Norman; Schindler, Johannes; Bera, Soumya; Solomon, Gemma C.; Evers, Ferdinand

    2016-08-01

    The density of states ϱ (E ) of graphene is investigated within the tight-binding (Hückel) approximation in the presence of vacancies. They introduce a nonvanishing density of zero modes nzm that act as midgap states, ϱ (E ) =nzmδ (E ) +smooth . As is well known, the actual number of zero modes per sample can, in principle, exceed the sublattice imbalance, Nzm≥|NA-NB| , where NA,NB denote the number of carbon atoms in each sublattice. In this paper, we establish a stronger relation that is valid in the thermodynamic limit and that involves the concentration of zero modes, nzm>|cA-cB| , where cA and cB denote the concentration of vacancies per sublattice; in particular, nzm is nonvanishing even in the case of balanced disorder, NA/NB=1 . Adopting terminology from benzoid graph theory, the excess modes associated with the current carrying backbone (percolation cluster) are called supernumerary. In the simplest cases, such modes can be associated with structural elements such as carbon atoms connected with a single bond, only. Our result suggests that the continuum limit of bipartite hopping models supports nontrivial "supernumerary" terms that escape the present continuum descriptions.

  4. The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

    Energy Technology Data Exchange (ETDEWEB)

    Cioni, C.; De Palma, F.; De Vito, L.; Stefanelli, A. [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell`Uomo

    1997-12-31

    In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

  5. Clinical management of supernumerary teeth: A report of two cases

    Directory of Open Access Journals (Sweden)

    Mittal M

    2010-09-01

    Full Text Available Supernumerary tooth may closely resemble the teeth of the group to which it belongs, i.e. molars, premolars or anterior teeth, or it may bear little resemblancein size or shape to which it is associated. Many complications can be associated with supernumeraries, like impaction, delayed eruption or ectopic eruption of adjacent teeth, crowding, development of median diastema and eruption into floor of the nasal cavity. This may also cause the formation of follicular cysts with significant bone destruction. Early intervention to remove it is usually required to obtain reasonable alignment and occlusal relationship. This article will present the clinical management of an (i impacted supernumerary tooth impeding the eruption of maxillary central incisor and (ii erupted supernumerary tooth with midline diastema.

  6. Multiple Geminated Supernumerary Premolars: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Atul Soin

    2015-01-01

    Full Text Available Supernumerary teeth may be defined as any teeth or tooth substance in excess of the usual configuration of 20 deciduous and 32 permanent teeth. Gemination is defined as an attempt by a single tooth bud to divide, with a resultant formation of either a large tooth with a bifid crown or two completely divided teeth throughout the crown and root. Geminated supernumerary premolar is a rarity and the possibility of multiple occurrences is even rarer. An exhaustive review of English literature and a PubMed search conducted using the terms “gemination’’ and “multiple geminated supernumerary” revealed no case of multiple geminated supernumerary premolars. We report a case of multiple geminated supernumerary premolars in a 23-year-old male.

  7. Multiple Geminated Supernumerary Premolars: A Rare Case Report

    Science.gov (United States)

    Soin, Atul; Sharma, Gaurav; Soin, Gayatri; Raina, Anudeep; Mutneja, Puneet; Nagpal, Archna

    2015-01-01

    Supernumerary teeth may be defined as any teeth or tooth substance in excess of the usual configuration of 20 deciduous and 32 permanent teeth. Gemination is defined as an attempt by a single tooth bud to divide, with a resultant formation of either a large tooth with a bifid crown or two completely divided teeth throughout the crown and root. Geminated supernumerary premolar is a rarity and the possibility of multiple occurrences is even rarer. An exhaustive review of English literature and a PubMed search conducted using the terms “gemination” and “multiple geminated supernumerary” revealed no case of multiple geminated supernumerary premolars. We report a case of multiple geminated supernumerary premolars in a 23-year-old male. PMID:26078889

  8. Rare occurrence of bilaterally impacted mandibular supernumerary teeth

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Bhardwaj

    2012-01-01

    Full Text Available Introduction: Supernumerary teeth are present in addition to the normal complement of teeth in permanent or deciduous dentitions. Incidence is high in permanent dentition, affects both the gender. They are more common in males, with the male to female ratio of 2:1. When the supernumerary teeth are causing problems such as, extensive resorption of adjacent teeth, hindering the eruption or malposition of permanent teeth, early surgical intervention is recommended. Case Report: A case of bilaterally impacted supernumerary premolars was reported when an orthopentomograph view was taken which revealed the presence of additional teeth impacted in relation to 35-36 and 45-46. Surgical removal was done as they were resorbing the roots of teeth in their vicinity. Discussion: Literature reports increased occurrence of the supernumeraries in the maxilla but supernumerary premolars are more likely to develop in the mandible. Etiology of supernumerary teeth is ambiguous and is due to following conditions:atavism or reversion, heredity, aberrations during embryologic formation, progress zone, and unified etiologic explanation.

  9. Computing along the axon

    Institute of Scientific and Technical Information of China (English)

    Chen Haiming; Tseren-Onolt Ishdorj; Gheorghe Pǎun

    2007-01-01

    A special form of spiking neural P systems, called axon P systems, corresponding to the activity of Ranvier nodes of neuron axon, is considered and a class of SN-like P systems where the computation is done along the axon is introduced and their language generative power is investigated.

  10. Small Supernumerary Marker Chromosomes in Human Infertility.

    Science.gov (United States)

    Armanet, Narjes; Tosca, Lucie; Brisset, Sophie; Liehr, Thomas; Tachdjian, Gérard

    2015-01-01

    Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by banding cytogenetics. The objective of this study was to provide an overview of sSMC frequency and characterization in a context of infertility and to review the literature describing sSMC in relation with male and female infertility. Therefore, a systematic literature review on sSMC associated with infertility was conducted by means of a PubMed literature and a sSMC database (http://ssmc-tl.com/sSMC.html) search. A total of 234 patients with infertility were identified as carriers of sSMC. All chromosomes, except chromosomes 10, 19 and the X, were involved in sSMC, and in 72% the sSMC originated from acrocentric chromosomes. Euchromatic imbalances were caused by the presence of sSMC in 30% of the cases. Putative genes have been identified in only 1.2% of sSMC associated with infertility. The implication of sSMC in infertility could be due to a partial trisomy of some genes but also to mechanical effects perturbing meiosis. Further precise molecular and interphase-architecture studies on sSMC are needed in the future to characterize the relationship between this chromosomal anomaly and human infertility.

  11. Non-syndrome associated multiple supernumerary teeth: A report of two cases

    Directory of Open Access Journals (Sweden)

    Nayak Ullal

    2006-05-01

    Full Text Available Multiple supernumerary teeth are usually associated with syndromes. On the contrary, multiple supernumerary teeth without association with any syndromes are very rare. This article presents a report of two cases with multiple supernumerary teeth not associated with any syndrome and emphasizes the routine advice of orthopantomogram whenever a single supernumerary tooth is detected irrespective of whether the patient has any syndrome or not.

  12. Whole-exome sequencing analysis of supernumerary teeth occurrence in Japanese individuals.

    Science.gov (United States)

    Takahashi, Masahiro; Hosomichi, Kazuyoshi; Yamaguchi, Tetsutaro; Yano, Keisuke; Funatsu, Takahiro; Adel, Mohamed; Haga, Shugo; Maki, Koutaro; Tajima, Atsushi

    2017-01-01

    A common disorder of human dentition is the existence of supernumerary teeth. Impacted supernumerary teeth occur most frequently in the maxillary incisor area and are termed mesiodens. We conducted whole-exome sequencing of non-syndromic Japanese individuals possessing supernumerary teeth to identify genes and/or loci involved in the pathogenesis of the condition.

  13. Late-Developing Supernumerary Premolars: Analysis of Different Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Sergio Paduano

    2016-01-01

    Full Text Available This case series describes the different potential approaches to late-developing supernumerary premolars (LDSP. LDSP are supernumerary teeth (ST formed after the eruption of the permanent dentition; usually they develop in the premolar region of the upper and lower jaw. The choice to extract or to monitor the LDSP depends on many factors and has to be carefully planned due to the several risks that either the monitoring or the extraction could provoke. These four cases of LDSP showed different treatment plan alternatives derived from a scrupulous assessment of the clinical and radiographic information.

  14. Unique case of a geminated supernumerary tooth with trifid crown

    Energy Technology Data Exchange (ETDEWEB)

    Ather, Amber; Ather, Hunaiza; Sheth, Sanket Milan; Muliya, Vidya Saraswathi [Manipal College of Dental Sciences, Manipal (Korea, Republic of)

    2012-09-15

    Gemination, a relatively uncommon dental anomaly, is characterized by its peculiar representation as a tooth with a bifid crown and a common root and root canal. It usually occurs in primary dentition. To come across gemination in a supernumerary tooth is a rare phenomenon. The purpose of this paper is to present a unique case of hyperdontia wherein gemination in an impacted supernumerary tooth resulted in a trifid crown unlike the usual bifid crown. The role of conventional radiographs as well as computed tomography, to accurately determine the morphology and spatial location, and to arrive at a diagnosis, is also emphasized in this paper.

  15. Supernumerary Teeth in Primary Dentition and Early Intervention: A Series of Case Reports

    Science.gov (United States)

    Bahadure, Rakesh N.; Thosar, Nilima; Jain, Eesha S.; Kharabe, Vidhi; Gaikwad, Rahul

    2012-01-01

    Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stages. They are of great concern to the dentists and parents because of the eruption, occlusal, and esthetic problems they can cause. Supernumerary teeth occur more frequently in the permanent dentition but rarely in primary dentition. Mesiodens is the most common type of supernumerary teeth but rarely seen in lower arch. Early recognition and diagnosis of supernumerary teeth is important to prevent further complications in permanent dentition. Four cases of supernumerary teeth with mesiodens in upper and lower arch in primary dentition and their management have been discussed. PMID:22888456

  16. Supernumerary Teeth in Primary Dentition and Early Intervention: A Series of Case Reports

    Directory of Open Access Journals (Sweden)

    Rakesh N. Bahadure

    2012-01-01

    Full Text Available Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stages. They are of great concern to the dentists and parents because of the eruption, occlusal, and esthetic problems they can cause. Supernumerary teeth occur more frequently in the permanent dentition but rarely in primary dentition. Mesiodens is the most common type of supernumerary teeth but rarely seen in lower arch. Early recognition and diagnosis of supernumerary teeth is important to prevent further complications in permanent dentition. Four cases of supernumerary teeth with mesiodens in upper and lower arch in primary dentition and their management have been discussed.

  17. Supernumerary teeth in primary dentition and early intervention: a series of case reports.

    Science.gov (United States)

    Bahadure, Rakesh N; Thosar, Nilima; Jain, Eesha S; Kharabe, Vidhi; Gaikwad, Rahul

    2012-01-01

    Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stages. They are of great concern to the dentists and parents because of the eruption, occlusal, and esthetic problems they can cause. Supernumerary teeth occur more frequently in the permanent dentition but rarely in primary dentition. Mesiodens is the most common type of supernumerary teeth but rarely seen in lower arch. Early recognition and diagnosis of supernumerary teeth is important to prevent further complications in permanent dentition. Four cases of supernumerary teeth with mesiodens in upper and lower arch in primary dentition and their management have been discussed.

  18. Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20.

    Science.gov (United States)

    Guediche, N; Brisset, S; Benichou, J-J; Guérin, N; Mabboux, P; Maurin, M-L; Bas, C; Laroudie, M; Picone, O; Goldszmidt, D; Prévot, S; Labrune, P; Tachdjian, G

    2010-02-01

    The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.

  19. Supernumerary ring chromosome 17 identified by fluorescent in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Fagan, K. [Hunter Area Pathology Service, New South Wales (Australia); Edwards, M. [Western Suburbs Hospital, New South Wales (Australia)

    1997-04-14

    We present a patient with multiple anomalies and severe developmental delay. A small supernumerary ring chromosome was found in 40% of her lymphocyte cells at birth. The origin of the marker chromosome could not be determined by GTG banding, but fluorescent in situ hybridization (FISH) later identified the marker as deriving from chromosome 17. 20 refs., 2 figs., 1 tab.

  20. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  1. BILATERAL MOLARIFORM SUPERNUMERARY TEETH IN THE ANTERIOR MAXILLA: A REPORT OF TWO CASES

    Directory of Open Access Journals (Sweden)

    Mehmet Cem ÖZDEN

    2017-01-01

    Full Text Available Supernumerary teeth are additional teeth besides the normal series and can be found in any region of the dental arch. Supernumerary teeth can be classified according to their form and locations. Early diagnosis and treatment of patients with supernumerary teeth may prevent or minimize complications. The treatment options depend on the type and position of the supernumerary tooth and its effect on the adjacent structures. Two male patients were referred to our clinic due to swelling in their maxillae and interrupted eruption of teeth. Upon radiological examination of the patients, impacted supernumerary teeth were found. Surgical removal of these teeth were perfomed and they were found to be molariform. We aim to present the two rare cases of molariform supernumerary teeth in this article.

  2. Múltiples dientes supernumerarios distomolares Multiple distomolars supernumerary teeth

    Directory of Open Access Journals (Sweden)

    F.J. Rodríguez Romero

    2009-12-01

    Full Text Available En una dentición normal, los dientes supernumerarios son aquellos descritos como adicionales a la serie. La etiología no esta clara. Se han descritos tanto en dentición primaria como en permanente, aunque son mas frecuentes en la dentición permanente. El objetivo de este informe es presentar un caso de una paciente con múltiples dientes supernumerarios distomolares. Cuartos molares bilaterales simétricos son sumamente raros.Supernumerary teeth are described as the teeth formed in excess of the number found in a normal dentition. The aetiology is not clear. Have been reported in both the primary and permanent dentition, although they are more prevalent in the permanent dentition. The purpose of this case report is to present a case of female patient with multiple distomolars supernumerary teeth. Bilateral symmetrical impacted fourth molars exceedingly uncommon.

  3. Axons take a dive

    Science.gov (United States)

    Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2015-01-01

    In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

  4. An observational study of the frequency of supernumerary teeth in a population of 2000 patients

    OpenAIRE

    Leco Berrocal, María Isabel; Martín Morales, José F.; Martínez González, José María

    2007-01-01

    An evaluation is made of the epidemiological characteristics of supernumerary teeth, with an analysis of the associated clinical-eruptive complications. A longitudinal observational study was made of 2000 patients, with the documentation of demographic data, the presence of supernumerary teeth, their location, mechanical accidents and the presence of associated pathology. The presence of supernumerary teeth was recorded in 1.05% of the study subjects (mean age 20.2 years), with a greater freq...

  5. Mesiodens with an unusual morphology and multiple impacted supernumerary teeth in a non-syndromic patient.

    Science.gov (United States)

    Srivatsan, Pavithra; Aravindha Babu, N

    2007-01-01

    Supernumerary teeth are a relatively frequent disorder of odontogenesis characterized by an excess number of teeth. Mesiodens is the most common type of supernumerary tooth found in the premaxilla between the two central incisors. They can be supplemental (resembling natural teeth), conical, tuberculate or molariform. We present the case of a 19 year-old girl who presented with a mesiodens of an unusual morphology and multiple impacted supernumerary teeth not associated with any syndrome.

  6. Mesiodens with an unusual morphology and multiple impacted supernumerary teeth in a non-syndromic patient

    Directory of Open Access Journals (Sweden)

    Srivatsan Pavithra

    2007-01-01

    Full Text Available Supernumerary teeth are a relatively frequent disorder of odontogenesis characterized by an excess number of teeth. Mesiodens is the most common type of supernumerary tooth found in the premaxilla between the two central incisors. They can be supplemental (resembling natural teeth, conical, tuberculate or molariform. We present the case of a 19 year-old girl who presented with a mesiodens of an unusual morphology and multiple impacted supernumerary teeth not associated with any syndrome.

  7. Axonal bleb recording

    Institute of Scientific and Technical Information of China (English)

    Wenqin Hu; Yousheng Shu

    2012-01-01

    Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments.The cell body and relatively thick dendrites are the most accessible compartments of a neuron,due to their large diameters and therefore great membrane surface areas.However,axons are normally inaccessible to patch pipettes because of their thin structure; thus studies of axon physiology have long been hampered by the lack of axon recording methods.Recently,a new method of patchclamp recording has been developed,enabling direct and tight-seal recording from cortical axons.These recordings are performed at the enlarged structure (axonal bleb) formed at the cut end of an axon after slicing procedures.This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal,the action potential,and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode.

  8. Prevalence and characteristics of supernumerary teeth in a non-syndromic South Indian pediatric population

    Directory of Open Access Journals (Sweden)

    Rajesh T Anegundi

    2014-01-01

    Full Text Available Background: Supernumerary teeth are one of the most widely reported and significant anomaly in patients affecting the primary and early mixed dentition. Aim: To describe the distribution and characteristics of the supernumerary teeth in South Indian population of paediatric patients. Design: In a 12 year retrospective study, a total of 63,569 patients up to the age of 14 years who visited our department between June 2003 and May 2013 were revised.790 cases of supernumerary teeth were found. Patients were evaluated for age, sex, site, status of dentition, number, position, orientation and type of supernumerary teeth. Statistical analysis was carried out using chi square test. Results: 790 subjects with supernumerary teeth (481 males and 309 females were detected, revealing male-female ratio of 1.55:1.The most common supernumerary teeth were mesiodens (82.28%, the most common site was the anterior maxilla (92.53%region. Majority of patients had a single erupted supernumerary oriented straight in the arch. Patients in mixed dentition stage reported with maximum number of supernumerary teeth. Conclusions: The prevalence of supernumerary teeth in non syndromicSouth Indian paediatric population is 1.24% with slight male predilection and conical mesiodens being the commonest.

  9. Prevalence and characteristics of supernumerary teeth in a non-syndromic South Indian pediatric population.

    Science.gov (United States)

    Anegundi, Rajesh T; Tegginmani, Veeresh S; Battepati, Prashant; Tavargeri, Anand; Patil, Shruthi; Trasad, Vijay; Jain, Garima

    2014-01-01

    Supernumerary teeth are one of the most widely reported and significant anomaly in patients affecting the primary and early mixed dentition. To describe the distribution and characteristics of the supernumerary teeth in South Indian population of paediatric patients. In a 12 year retrospective study, a total of 63,569 patients up to the age of 14 years who visited our department between June 2003 and May 2013 were revised.790 cases of supernumerary teeth were found. Patients were evaluated for age, sex, site, status of dentition, number, position, orientation and type of supernumerary teeth. Statistical analysis was carried out using chi square test. 790 subjects with supernumerary teeth (481 males and 309 females) were detected, revealing male-female ratio of 1.55:1.The most common supernumerary teeth were mesiodens (82.28%), the most common site was the anterior maxilla (92.53%)region. Majority of patients had a single erupted supernumerary oriented straight in the arch. Patients in mixed dentition stage reported with maximum number of supernumerary teeth. The prevalence of supernumerary teeth in non syndromic South Indian paediatric population is 1.24% with slight male predilection and conical mesiodens being the commonest.

  10. Dentigerous cyst in a child associated with multiple inverted supernumerary teeth: a rare occurrence.

    Science.gov (United States)

    Agrawal, Neeraj K

    2012-01-01

    Dentigerous cysts associated with supernumerary teeth are rare with most of them developing around a mesiodens in the anterior maxilla. Dentigerous cysts from multiple supernumerary teeth, especially with inverted tooth, are rare in other regions of the maxilla. We report a unique case of a dentigerous cyst in a child associated with multiple inverted supernumerary teeth and relevant review of literarature. Dentigerous cyst arising from multiple supernumerary teeth and not anterior maxillary mesiodens is quite uncommon. In a child, such findings associated with inverted tooth are still rare. Such cysts should be managed by excision as soon as possible.

  11. Genetics and presence of non-syndromic supernumerary teeth: A mystery case report and review of literature

    OpenAIRE

    Neha Khambete; Rahul Kumar

    2012-01-01

    Presence of supernumerary teeth is well-recognized clinical phenomenon. However, it is uncommon to find multiple supernumeraries in individuals with no other associated disease or syndrome. Presence of multiple supernumerary teeth is thought to have genetic component. We report a rare case where multiple supernumerary teeth were seen without presence of any other syndrome in 3 generations; father, son, and two grandsons. We also present a review of similar cases published in literature till d...

  12. Diagnosis and Surgical Management of Nonsyndromic Nine Supernumerary Teeth and Leong's Tubercle.

    Science.gov (United States)

    Cruz, Christiane V; Soares, Andrea L; Braga, David N; Costa, Marcelo C

    2016-01-01

    Nonsyndromic multiple supernumerary teeth (ST) and Leong's tubercle are a condition with a very low prevalence and a multidisciplinary approach is required to restore function and aesthetics. So, this case report aimed at presenting a rare case of nonsyndromic nine supernumerary teeth and Leong's tubercle in a pediatric patient, without any evident familial history, showing its diagnosis and surgical management.

  13. Radiographic Follow-Up during Orthodontic Treatment for Early Diagnosis of Sequential Supernumerary Teeth

    Science.gov (United States)

    Suga, Uhana Seifert Guimarães; Terada, Raquel Sano Suga

    2016-01-01

    Most supernumerary teeth are impacted and asymptomatic. Objective. The aim of this paper is to describe two cases of sequential development of supernumerary teeth in the mandibular premolar region, identified during orthodontic treatment. Reports. The first case describes the radiographic follow-up of a female patient that presented a supernumerary tooth at the age of 9 years and 10 months in the right mandibular premolar region, followed by a further supernumerary tooth in the left mandibular premolar region identified at the age of 11 years and 3 months. In the second case, the radiographic follow-up of a male patient demonstrated 3 supernumerary teeth in the premolar region at the age of 16 years. During orthognathic surgery planning at the age of 20 years and 5 months, a supplemental supernumerary tooth was found in the left mandibular region. Conclusion. Considering the late developing of supernumerary premolars, appropriate follow-up with panoramic radiographs of patients with previous experience of supernumerary teeth is essential for early diagnosis of supplemental premolars to prevent possible complications. PMID:27313911

  14. Prevalence of impacted and supernumerary teeth in the North Indian population.

    Science.gov (United States)

    Patil, Santosh; Maheshwari, Sneha

    2014-04-01

    Dental impaction is a very frequent problem. Supernumerary teeth, or hyperdontia, are the presence of additional teeth to the normal series in the either of the dentition. The presence of impacted and/or supernumerary teeth can cause various complications. The objective of the present study was to determine the prevalence of impacted and supernumerary teeth in the North Indian population. The panoramic radiographic records of 4750 patients attending the Department of Oral Medicine and Radiology, Jodhpur Dental College General Hospital between September 2008 to December 2012 were examined for this retrospective study. The ages of the patients ranged from 8 to 72 years, with a mean of 34.6 years. A total of 798 (16.8%) patients presented with 1126 impacted teeth. Impacted canines were the most prevalent (9.7%), followed by impacted premolars (4.3%). Supernumerary teeth (1.6%) and impacted molars (1.2%) were less prevalent. Among the 842 impacted teeth, the most frequently affected teeth were the canines (56.7%), followed by premolars (27.8%), and supernumerary teeth (9.3%), while the prevalence of impacted molars was quite lower (6.2%). The most frequently impacted teeth were maxillary canines and the mesiodens were the most common supernumerary tooth. The early diagnosis of supernumerary and impacted teeth is essential to prevent malocclusion and malalignment of permanent teeth demonstrating the importance of panoramic radiographs in their detection. Key words:Impacted, supernumerary, prevalence, canines, mesiodens.

  15. Prevalence of supernumerary teeth in a nonsyndromic Syrian sample.

    Science.gov (United States)

    Burhan, Ahmad S; Nawaya, Fehmieh R; Arabi Katbi, Mohammad E; Al-Jawabra, Alaa S

    2015-12-01

    Supernumerary teeth (ST), also known as hyperdontia, is a condition in which more than the normal number of teeth are present in the series. The prevalence of ST varies between and within different populations. These teeth may cause various complications. The aim of the current study was to investigate the prevalence and characteristics of ST in Damascus inhabitants, Syria. A cross-sectional study was carried out using retrospectively collected digital panoramic radiographs of 2753 patients (1047 males and 1706 females) ranging in age from 12.2 to 20.5 years between January 2012 and December 2014. These radiographs were obtained from private dental offices spread across Damascus, Syria. For each patient with ST, the demographic variables, number, location, type, position, morphology of ST, and complications were recorded. ST were detected in 39 patients (1.4%), of whom 25 (64.1%) were males and 14 (35.9%) were females, with a male to female ratio of 1.8 : 1 (PMesiodens was the most prevalent ST (39.1%), followed by supernumerary premolars (28.3%), supernumerary laterals (26.1%), distomolars (4.3%), and paramolars (2.2%). This series includes cases with one and two ST. Of the 46 ST detected, 56.5% had a conical morphology, 89.1% were in a vertical position, and 19.6% were erupted. ST caused displacement of the adjacent teeth in 17 cases (37.0%) and the impaction of the permanent teeth in five cases (10.9%). The prevalence of ST in Damascus inhabitants was found to be 1.4%; the most frequent type was mesiodens. A conical morphology was found to be the most common form of ST. Displacement of permanent teeth is the most frequent complication. Further studies should be carried out on more representative samples of both the public and the private sector patients.

  16. Non-syndromic multiple supernumerary premolars: Clinicoradiographic report of five cases

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    Renu Tanwar

    2017-03-01

    Full Text Available Hyperdontia or supernumerary teeth in both arches without any syndromic manifestation are extremely rare. Supernumerary teeth are commonly associated with Gardner’s syndrome, cleft lip and palate, cleidocranial dysplasia and trichorhinopha-langeal syndrome. Five cases of non-syndromic multiple premolars of maxillary and mandibular arches in Indian patients are presented here. This case series reports three cases with multiple (9 in maximum, bilaterally impacted and erupted supernumerary teeth and two cases with supernumerary premolars in non-syndromic cases from Indian patients. Supernumerary teeth can be present in any region of the oral cavity. Although the occurrence of maxillary para-premolars is rare, radio-logical investigations play a major and decisive role in determining the management of such cases.

  17. The study of impacted and supernumerary teeth in young man by the full mouth roentgenograms

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hung Kyu [Department of Dental Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1977-11-15

    The author has observed 906 full mouth roentgenograms in Korean young man who had the impacted and supernumerary teeth. Impacted and supernumerary teeth were analysed upon several items, such as incidences and positions in the dental arch . The results were as follows; 1. The incidences of impacted teeth were 59.05%, and the ratio of upper jaw to lower one was 1:3. 2. The frequency of the supernumerary teeth were 5.52%, and the ratio of maxilla to mandible was 49:1. 3. No significant differences between right and left side in both jaws, but incidence rate of the supernumerary teeth was 74% in the maxillary central incisor area. 4. The positions of impacted and supernumerary teeth were vertical and inverted shapes in maxilla, whereas horizontal a nd mesio-angular forms in mandible.

  18. Cystic Endometrioma with Coexisting Fibroma Originating in a Supernumerary Ovary in the Rectovaginal Pouch

    Science.gov (United States)

    Sakaguchi, Asumi; Kodama, Hiroko; Ogura, Kanako; Miwa, Ayako; Sugimori, Yayoi; Matuoka, Shozo; Matsumoto, Toshiharu

    2017-01-01

    A supernumerary ovary is an exceedingly rare disorder, in which the structure containing ovarian tissue is located at some distance from the normally placed ovary. 16 cases of endometriosis or tumors originating in a supernumerary ovary have been published in the English literature, but no case of coexisting endometriosis and a tumor has been published. We present the case of a 40-year-old female with cystic endometrioma with coexisting fibroma originating in a supernumerary ovary in the rectovaginal pouch. The present case is the first to be reported with coexisting endometriosis and a tumor originating in a supernumerary ovary. Our experience with this case and the results of our previous studies of rectovaginal endometriosis indicated that the possibility of originating in a supernumerary ovary shall be examined in cases of cystic endometrioma in the rectovaginal pouch. PMID:28210515

  19. Múltiples dientes supernumerarios distomolares Multiple distomolars supernumerary teeth

    OpenAIRE

    F.J. Rodríguez Romero; S. Cerviño Ferradanes

    2009-01-01

    En una dentición normal, los dientes supernumerarios son aquellos descritos como adicionales a la serie. La etiología no esta clara. Se han descritos tanto en dentición primaria como en permanente, aunque son mas frecuentes en la dentición permanente. El objetivo de este informe es presentar un caso de una paciente con múltiples dientes supernumerarios distomolares. Cuartos molares bilaterales simétricos son sumamente raros.Supernumerary teeth are described as the teeth formed in excess of th...

  20. Glia to axon RNA transfer.

    Science.gov (United States)

    Sotelo, José Roberto; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José Roberto; Calliari, Aldo; Cal, Karina; Bresque, Mariana; Dipaolo, Andrés; Farias, Joaquina; Mercer, John A

    2014-03-01

    The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased.

  1. Genetics and presence of non-syndromic supernumerary teeth: A mystery case report and review of literature.

    Science.gov (United States)

    Khambete, Neha; Kumar, Rahul

    2012-10-01

    Presence of supernumerary teeth is well-recognized clinical phenomenon. However, it is uncommon to find multiple supernumeraries in individuals with no other associated disease or syndrome. Presence of multiple supernumerary teeth is thought to have genetic component. We report a rare case where multiple supernumerary teeth were seen without presence of any other syndrome in 3 generations; father, son, and two grandsons. We also present a review of similar cases published in literature till date. The role of genetics in development of supernumerary teeth is highlighted.

  2. Genetics and presence of non-syndromic supernumerary teeth: A mystery case report and review of literature

    Directory of Open Access Journals (Sweden)

    Neha Khambete

    2012-01-01

    Full Text Available Presence of supernumerary teeth is well-recognized clinical phenomenon. However, it is uncommon to find multiple supernumeraries in individuals with no other associated disease or syndrome. Presence of multiple supernumerary teeth is thought to have genetic component. We report a rare case where multiple supernumerary teeth were seen without presence of any other syndrome in 3 generations; father, son, and two grandsons. We also present a review of similar cases published in literature till date. The role of genetics in development of supernumerary teeth is highlighted.

  3. Surgical management of multiple supernumerary teeth and an impacted maxillary permanent central incisor.

    Science.gov (United States)

    Rallan, Mandeep; Rallan, Neelakshi Singh; Goswami, Mousumi; Rawat, Kamini

    2013-05-22

    Hyperdontia is the condition of having supernumerary teeth, or teeth which appear in addition to the regular number of teeth. It is a developmental anomaly and has been argued to arise from multiple aetiologies. The most common site is the maxillary incisor region; but the prevalence of more than three teeth supernumerary tooth is less than 1%. A case of 13 year male patient is reported with a multiple impacted supernumerary tooth in maxillary anterior region hindering the eruption of right permanent central incisor. The supernumerary tooth was treated via surgical approach followed by an interim prosthesis for permanent central incisor which later on erupted in due course of time. Background Supernumerary teeth may be defined as any teeth or tooth substance in excess of the usual configuration of 20 deciduous and 32 permanent teeth. The presence of supernumerary teeth in the premaxillary region often poses unique diagnostic and managerial concerns for the practitioner. Rarely is the surplus number compensated by an absence or deficiency of other teeth. Therefore, the dysfunctional nature of supernumerary teeth and their ability to create a variety of pathological disturbances in the normal eruption and position of adjacent teeth warrants their early detection and prudent management. Approximately 76-86% of cases represent single-tooth hyperdontia, with two supernumerary teeth noted in 12-23% and three or more extra teeth noted in less than 1% of cases. Multiple supernumerary teeth are also associated with many syndromes like cleidocranial dysplasia and Gardner’s syndrome etc. However, it is rare to find multiple supernumeraries in individuals with no other associated disease or syndrome. In such cases, the maxillary anterior region is the common site of occurrence. The exact aetiology is not clearly understood. The supernumerary teeth result from any disturbance in the initiation and proliferation stages of odontogenesis. There are several theories regarding the

  4. Multiple supernumerary teeth and odontoma in the maxilla: A case report

    Directory of Open Access Journals (Sweden)

    P B Sood

    2010-01-01

    Full Text Available Most supernumerary impacted teeth are located in the anterior maxillary region. They are classified according to their form and location. Their presence may give rise to a variety of clinical problems. The detection of supernumerary teeth is best achieved by thorough clinical and radiographic examination. Their management should form part of a comprehensive treatment plan. This article presents an overview of the diagnostic problems associated with multiple supernumerary impacted teeth and includes a discussion of the classification, diagnosis, and management of this difficult clinical entity.

  5. Multiple supernumerary teeth associated with an impacted maxillary central incisor: Surgical and orthodontic management

    Directory of Open Access Journals (Sweden)

    Ramakrishna Yeluri

    2012-01-01

    Full Text Available Various anomalies in the size, shape, number, structure and eruption of the teeth are often observed clinical conditions. Supernumerary teeth can be found in almost any region of the dental arch, and most of the times they are asymptomatic, and are routinely found during radiographic evaluation. The most common cause of impacted maxillary incisors is the presence of the supernumerary teeth. This paper describes a case of multiple supernumerary teeth associated with an impacted permanent maxillary central incisor in an 11-year old child along with its surgical and orthodontic management.

  6. Supernumerary ring chromosome: an etiology for Pallister-Killian syndrome?

    Science.gov (United States)

    Lloveras, E; Canellas, A; Cirigliano, V; Català, V; Cerdan, C; Plaja, A

    2013-01-01

    Characterization of marker chromosomes before the introduction of array CGH (aCGH) assays was only based on their banding patterns (G, C, and NOR staining) and fluorescent in situ hybridization techniques. The use of aCGH greatly improves the identification of marker chromosomes in some cases. We describe an atypical case of Pallister-Killian syndrome (PKS) detected at prenatal diagnosis with a very unusual cytogenetic presentation: a supernumerary ring chromosome including two copies of 12p. A similar anomaly described in a postnatal patient suggests ring chromosome as a possible cause of PKS. Extra ring chromosomes might be a more common etiology for PKS than previously thought, given the difficulty in their characterization before the advent of aCGH.

  7. Four miniature kidneys: supernumerary kidney and multiple organ system anomalies.

    Science.gov (United States)

    Afrouzian, Marjan; Sonstein, Joseph; Dadfarnia, Tahereh; Sreshta, J Nicholas; Hawkins, Hal K

    2014-05-01

    More than 350 years after Martius's first reported case in 1656, supernumerary kidney (SNK) continues to fascinate the world of medicine, generating new ideas in the domain of embryogenesis. Association of a normal kidney with a second or third ipsilateral smaller kidney is an extremely rare anomaly with only a total of 81 cases reported until today. We are reporting a case of SNK, clinically diagnosed as right hydronephrosis, associated with an ipsilateral ectopic ureter, a contralateral partially duplicated ureter, and a multiseptate gallbladder. Pathologic examination of the nephrectomy revealed 4 miniature kidneys, joining a dilated ureter through 4 separate conduits. Our patient is the first reported case of SNK with absent ipsilateral normal kidney, presence of more than 3 kidneys on 1 side, and associated anomaly in the gallbladder. This case represents a unique combination of rarities, suggesting insights in the domain of molecular embryology.

  8. Microfluidic control of axonal guidance

    Science.gov (United States)

    Gu, Ling; Black, Bryan; Ordonez, Simon; Mondal, Argha; Jain, Ankur; Mohanty, Samarendra

    2014-10-01

    The precision of axonal pathfinding and the accurate formation of functional neural circuitry are crucial for an organism during development as well as during adult central and peripheral nerve regeneration. While chemical cues are believed to be primarily responsible for axonal pathfinding, we hypothesize that forces due to localized fluid flow may directly affect neuronal guidance during early organ development. Here, we report direct evidence of fluid flow influencing axonal migration, producing turning angles of up to 90°. Microfluidic flow simulations indicate that an axon may experience significant bending force due to cross-flow, which may contribute to the observed axonal turning. This method of flow-based guidance was successfully used to fasciculate one advancing axon onto another, showcasing the potential of this technique to be used for the formation of in vitro neuronal circuits.

  9. Endoscopic Removal of a Supernumerary Premolar in the Mandible during a Dental Implant Placement

    Directory of Open Access Journals (Sweden)

    Víctor Beltrán

    2014-01-01

    Full Text Available The surgical removal of supernumerary teeth is necessary in some cases, especially before the commencement of any orthodontic or implant treatment procedure. In the mandibular supernumerary premolar, a more conservative approach is required because of the presence of complications associated with conventional surgery due to the close proximity of the said premolar to the alveolar inferior and mental nerves, and the need for bone conservation for implant placement. The endoscopic surgical approach has been used for the removal of the maxillary supernumerary tooth, impacted third molar, and implants. In this case report, we present an endoscopically assisted surgical technique for the removal of an unerupted supernumerary premolar in the mandible associated with a dental implant placement procedure.

  10. The membrane effects, and sensitivity to strychnine, of neural inhibition of the Mauthner cell, and its inhibition by glycine and GABA

    Science.gov (United States)

    Diamond, J.; Roper, S.; Yasargil, G. M.

    1973-01-01

    1. Anionic conductance changes in Mauthner neurones of goldfish were measured during synaptically evoked inhibition and inhibition caused by iontophoretic application of the putative inhibitory transmitters glycine and γ-aminobutyric acid (GABA). 2. The effects of either amino acid were indistinguishable from those of the neural inhibitory transmitter(s). The membrane permeability during the neural or drug response was increased to Br-, Cl-, I-, SCN-, NO3-, ClO3-, and formate (HCOO-), but not to HCO3-, BrO3-, IO3-, SO4-, HPO4-, H2PO4-, acetate and citrate. 3. Strychnine was injected intramuscularly, iontophoretically, or applied topically to the exposed brain in order to compare quantitatively its ability to prevent inhibition evoked by synaptic activation and by pharmacological means. Inhibitions were measured by the increase in membrane conductance. 4. Strychnine, at concentrations just adequate to block completely the late collateral inhibition (LCI) and crossed VIII nerve inhibition, had little effect on the pharmacological inhibition caused by glycine, and sometimes there was no detectable effect at all. In one experiment even a local iontophoretic application of strychnine in a sufficient dose to diffuse over the cell and block the LCI almost completely, merely halved the effect of a small dose of glycine applied to the same localized region of the membrane. 5. Higher concentrations of strychnine than those necessary to block synaptically evoked inhibition would reduce the effect of glycine but not that of GABA. The evidence indicated that any apparent effect of strychnine upon GABA could be explained by displacement of the GABA-containing iontophoretic pipette. 6. The glycine-blocking action of iontophoretic pulses of strychnine was of relatively very slow onset and long duration compared to the effects of pulses of glycine and GABA. 7. These findings can be interpreted as either (1) strychnine has a presynaptic action, preventing the release of inhibitory

  11. Agenesis of premolar associated with submerged primary molar and a supernumerary premolar: An unusual case report

    Directory of Open Access Journals (Sweden)

    S. V. S. G. Nirmala

    2012-01-01

    Full Text Available The combination of submerged primary molar, agenesis of permanent successor with a supernumerary in the same place is very rare. The purpose of this article is to report a case of submerged mandibular left second primary molar with supernumerary tooth in the same region along with agenesis of second premolar in an 11-year-old girl, its possible etiological factors, and a brief discussion on treatment options.

  12. Diagnosis and management of supernumerary (mesiodens): a review of the literature.

    Science.gov (United States)

    Meighani, G; Pakdaman, A

    2010-01-01

    Supernumerary tooth is one of the developmental problems in children. Mesiodens is a supernumerary tooth present in the midline between the two central incisors. It usually results in oral problems such as malocclusion, food impaction, poor aesthetics, and cyst formation. The prevalence of mesiodens varies between 0.09% and 2.05% in different studies. This paper reviews current literature on etiology, prevalence, diagnosis, and management of this problem. Accordingly, early diagnosis and treatment is suggested to prevent orthodontic and pathologic complications.

  13. Coexistent partial anodontia and supernumerary tooth in the mandibular arch: A rare case

    Directory of Open Access Journals (Sweden)

    Das G

    2006-05-01

    Full Text Available Coexistent partial anodontia and supernumerary tooth in the lower jaw is a very uncommon condition. Very few cases have been reported in the literature of this condition, etiology of which is still obscure. Presented here is a rare case of simultaneous presence of single supernumerary tooth together with missing permanent central incisor teeth in the lower jaw without any associated systemic condition or syndrome.

  14. Histological Evaluation and Management of Rare Case of Supernumerary “Ghost” Teeth

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    Dino Re

    2017-01-01

    Full Text Available Supernumerary teeth are teeth that exceed the normal dental formula. Their prevalence in the permanent dentition is 1–14% and they occur more frequently in maxilla with a sex ratio of 2 : 1 in favor of males. They are often associated with syndromes but there are examples of nonsyndromic multiple supernumerary teeth reported in the literature. CBCT is usually the best exam for radiographic diagnosis and treatment planning, because it provides 3D information about location and morphology of supernumerary teeth. This paper reports a rare case of four supernumerary teeth in a nonsyndromic 9-year-old boy. The peculiarity of this case is that two more exceeding teeth were found during surgical procedure. After extraction, all the teeth underwent a histological undecalcified processing for light microscopical examination. The two “ghost” supernumerary teeth seemed to be primordial dental germs, possibly resulting from an altered odontogenic process. After supernumerary teeth extraction, X-rays and exfoliation monitoring are recommended, since permanent retained teeth often erupt naturally or, at least, improve their condition. Radiographic follow-up is also useful in order to assess the formation of further teeth due to the hyperactivity of the dental lamina.

  15. Prevalence rate of supernumerary teeth among non-syndromic South Indian population: An analysis

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    M Nazargi Mahabob

    2012-01-01

    Full Text Available Aim: Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stage. The main objective of the study was to determine the prevalence rate of supernumerary teeth in the patients who reported to the Department of Oral Medicine and Radiology and to study the associated clinical complications. Materials and Methods: A longitudinal observational study was conducted of 2216 patients for a period of 4 months with the documentation of demographic data, the presence of supernumerary teeth, their location, and associated complications such as mechanical trauma, dental caries, and associated pathology. Results: The study recorded 27 supernumerary teeth from the examined 2216 patients. This yields a prevalence of 1.2%, with greater frequency in males which was 1.49% and in females the frequency was 0.85%. The greatest proportion of supernumerary teeth was found in the maxillary anterior region (77.8%. Out of this, 85.7% were classified as mesiodens based on their location. The displacement of adjacent teeth was the most common finding, followed by dental caries. Conclusion: The prevalence of supernumerary teeth in this study was 1.2% which is in agreement with that reported in similar studies and the maxillary mesiodens was the most common location. Displacement of adjacent teeth was the most common finding.

  16. Prevalence rate of supernumerary teeth among non-syndromic South Indian population: An analysis.

    Science.gov (United States)

    Mahabob, M Nazargi; Anbuselvan, G J; Kumar, B Senthil; Raja, S; Kothari, Sucitha

    2012-08-01

    Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stage. The main objective of the study was to determine the prevalence rate of supernumerary teeth in the patients who reported to the Department of Oral Medicine and Radiology and to study the associated clinical complications. A longitudinal observational study was conducted of 2216 patients for a period of 4 months with the documentation of demographic data, the presence of supernumerary teeth, their location, and associated complications such as mechanical trauma, dental caries, and associated pathology. The study recorded 27 supernumerary teeth from the examined 2216 patients. This yields a prevalence of 1.2%, with greater frequency in males which was 1.49% and in females the frequency was 0.85%. The greatest proportion of supernumerary teeth was found in the maxillary anterior region (77.8%). Out of this, 85.7% were classified as mesiodens based on their location. The displacement of adjacent teeth was the most common finding, followed by dental caries. The prevalence of supernumerary teeth in this study was 1.2% which is in agreement with that reported in similar studies and the maxillary mesiodens was the most common location. Displacement of adjacent teeth was the most common finding.

  17. The post-natal fate of supernumerary ribs in rat teratogenicity studies.

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    Wickramaratne, G A

    1988-04-01

    A common occurrence in rat teratology studies, supernumerary ribs, have been considered to be indicative of teratogenicity by some authors but not to be so indicative by others. As a teratogenic event is, by definition a permanent change, a study to follow the fate of supernumerary ribs in the development of adulthood of the rat was undertaken. An established teratogen in the rat, aspirin, was used to increase the frequency of supernumerary ribs. Even though aspirin treatment of the dams doubled the initial frequency of supernumerary ribs the results show that over the first 60 days post-partum their frequency in both control and treated groups decline to essentially zero. This decline in frequency of supernumerary ribs is complemented by an increase in the proportion of foetuses with a fully developed transverse process on the first lumbar vertebra. The proposal that supernumerary ribs in the rat are a result of developmental delays in a labile region of the axial skeleton and not a manifestation of a teratogenic event is presented.

  18. INVESTIGATION OF IMPACTED SUPERNUMERARY TEETH: A CONE BEAM COMPUTED TOMOGRAPH (CBCT STUDY

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    Gökhan GÜRLER

    2017-10-01

    Full Text Available Purpose: The purpose of this study was to investigate the impacted supernumerary teeth which were initially detected on panoramic radiographs by using cone beam computed tomography (CBCT. Materials and Methods: In this retrospective study, supernumerary teeth diagnosed on panoramic radiographs taken from patients who had admitted for routine dental treatment were evaluated using CBCT. Patients’ age, gender, systemic conditions as well as number of supernumerary teeth, unilateral-bilateral presence, anatomical localization (maxilla, mandible, anterior-premolar-molar, mesiodens-lateral-canine, parapremolar-paramolar-distomolar shape (rudimentary, supplemental, tuberculate, odontoma, position (palatal-lingual-buccal-labial-central, shortest distance between the tooth and adjacent cortical plate, complications and treatment were assessed. Results: A total of 47 impacted supernumerary teeth in 34 patients were investigated in this study. Of these, 33 (70.2% were unilateral and 14 (29.8% were bilateral. Only 1 supernumerary tooth was found in 27 patients (79.4% whereas 7 patients (20.6% had 2 or more supernumerary teeth. Most of the teeth located in the anterior region (74.4% of the jaws and maxilla (74.4%. Twenty teeth (42.5% were mesiodens, 11 (23.4% were lateral or canine, 14 (29.7% were parapremolar and 2(4.4% were distomolar. Twenty-seven teeth (57.4% were rudimentary, 15 (31.9% were supplemental and 5 (10.7% were odontoma in shape. The shortest distance between the supernumerary tooth and adjacent cortical plate varied between 0 to 2.5 mm with a mean of 0.66 mm. The most common clinical complaint was the non-eruption of permanent teeth (42.5%. All supernumerary teeth were removed under local anesthesia. Orthodontic traction was performed for those impacted permanent teeth if necessary. Conclusion: Impacted supernumerary teeth are usually in close proximity to cortical bone. Although this may facilitate surgical access, there is a risk of

  19. The genetics of axonal transport and axonal transport disorders.

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    Jason E Duncan

    2006-09-01

    Full Text Available Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.

  20. Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes

    Science.gov (United States)

    Liehr, Thomas; Karamysheva, Tatyana; Merkas, Martina; Brecevic, Lukrecija; Hamid, Ahmed B.; Ewers, Elisabeth; Mrasek, Kristin; Kosyakova, Nadezda; Weise, Anja

    2010-01-01

    Somatic mosaicism is something that is observed in everyday lives of cytogeneticists. Chromosome instability is one of the leading causes of large-scale genome variation analyzable since the correct human chromosome number was established in 1956. Somatic mosaicism is also a well-known fact to be present in cases with small supernumerary marker chromosomes (sSMC), i.e. karyotypes of 47,+mar/46. In this study, the data available in the literature were collected concerning the frequency mosaicism in different subgroups of patients with sSMC. Of 3124 cases with sSMC 1626 (52%) present with somatic mosaicism. Some groups like patients with Emanuel-, cat-eye- or i(18p)- syndrome only tend rarely to develop mosaicism, while in Pallister-Killian syndrome every patient is mosaic. In general, acrocentric and non-acrocentric derived sSMCs are differently susceptible to mosaicism; non-acrocentric derived ones are hereby the less stable ones. Even though, in the overwhelming majority of the cases, somatic mosaicism does not have any detectable clinical effects, there are rare cases with altered clinical outcomes due to mosaicism. This is extremely important for prenatal genetic counseling. Overall, as mosaicism is something to be considered in at least every second sSMC case, array-CGH studies cannot be offered as a screening test to reliably detect this kind of chromosomal aberration, as low level mosaic cases and cryptic mosaics are missed by that. PMID:21358988

  1. Small supernumerary marker chromosomes and their correlation with specific syndromes

    Science.gov (United States)

    Jafari-Ghahfarokhi, Hamideh; Moradi-Chaleshtori, Maryam; Liehr, Thomas; Hashemzadeh-Chaleshtori, Morteza; Teimori, Hossein; Ghasemi-Dehkordi, Payam

    2015-01-01

    A small supernumerary marker chromosome (sSMC) is a structurally abnormal chromosome. It is an additional chromosome smaller than one chromosome most often lacking a distinct banding pattern and is rarely identifiable by conventional banding cytogenetic analysis. The origin and composition of an sSMC is recognizable by molecular cytogenetic analysis. These sSMCs are seen in different shapes, including the ring, centric minute, and inverted duplication shapes. The effects of sSMCs on the phenotype depend on factors such as size, genetic content, and the level of the mosaicism. The presence of an sSMC causes partial tris- or tetrasomy, and 70% of the sSMC carriers are clinically normal, while 30% are abnormal in some way. In 70% of the cases the sSMC is de novo, in 20% it is inherited from the mother, and in 10% it is inherited from the father. An sSMC can be causative for specific syndromes such as Emanuel, Pallister-Killian, or cat eye syndromes. There may be more specific sSMC-related syndromes, which may be identified by further investigation. These 10 syndromes can be useful for genetic counseling after further study. PMID:26322288

  2. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

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    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  3. Mesiodens--diagnosis and management of a common supernumerary tooth.

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    Russell, Kathleen A; Folwarczna, Magdalena A

    2003-06-01

    Mesiodentes are the most common supernumerary teeth, occurring in 0.15% to 1.9% of the population. Given this high frequency, the general dentist should be knowledgeable about the signs and symptoms of mesiodentes and appropriate treatment. The cause of mesiodentes is not fully understood, although proliferation of the dental lamina and genetic factors have been implicated. Mesiodentes can cause delayed or ectopic eruption of the permanent incisors, which can further alter occlusion and appearance. It is therefore important for the clinician to diagnose a mesiodens early in development to allow for optimal yet minimal treatment. Treatment options may include surgical extraction of the mesiodens. If the permanent teeth do not erupt in a reasonable period after the extraction, surgical exposure and orthodontic treatment may be required to ensure eruption and proper alignment of the teeth. In some instances, fixed orthodontic therapy is also required to create sufficient arch space before eruption and alignment of the incisor(s). Early diagnosis allows the most appropriate treatment, often reducing the extent of surgery, orthodontic treatment and possible complications. This paper outlines the causes and modes of presentation of mesiodentes, and presents guidelines for diagnosis and management of nonsyndromic mesiodentes.

  4. Mirror imaging of impacted and supernumerary teeth in dizygotic twins: A case report.

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    Cassetta, Michele; Altieri, Federica; Giordano, Alessandra

    2015-02-01

    Mesiodens is the most common type of supernumerary tooth found in the premaxilla. It might be discovered by the clinical examination by chance on a radiograph or as the cause of an unerupted maxillary central incisor. The genetic transmission of supernumerary and impacted teeth is poorly understood. Mirror imaging in twins has been reported frequently in relation to several unilateral dental anomalies including mesiodens. This phenomenon is the appearance of an asymmetrical feature or anomaly occurring on the right side of one twin but on the left side of the other twin. The event of mesiodens mirror imaging in monozygotic twins has been described in literature. This is the first reported case of mesiodens mirror images in dizygotic twins. The de-scribed mesiodens caused the eruption failure of maxillary permanent incisors. The super-numerary teeth were removed to facilitate the spontaneous eruption of the impacted perma-nent maxillary incisors. Studies related to supernumerary teeth can be useful to clinicians in the early diagnosis of this anomaly. Clinical and radiographic examinations provide a correct therapeutic approach. Key words:Supernumerary teeth, twins, dental development.

  5. Multiple Supernumerary Teeth in a Non-Syndromic Patient: A Case Report

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    Majid Eshgh Pour

    2013-01-01

    Full Text Available Introduction: Multiple supernumerary teeth are a rare phenomenon. It occurs more often in patients with syndromes such as Gardner's syndrome, cleidocranial dysplasia and so on. This phenomenon in absence of such syndromes is rare. The purpose of this report was to introduce a case of non-syndromic multiple supernumerary impacted teeth.Case Report: A 29-year-old woman with no skeletal, metabolic, systemic and mental disorder was referred to oral and maxillofacial department of Mashhad dental school. In clinical evaluation, seven Permanent teeth were missing. In radiographic evaluation, there were a total of 15 impacted teeth which 7 of them were supernumerary.Conclusion: Missing or Excess of one or more teeth usually leads to occlusal and functional problems. In these cases, a complete clinical and radiographic examination accompanieal by a precise history should be performed to plan a suitable surgical-orthodontic-prosthetic treatment.

  6. Sequential supernumerary teeth development in a non-syndromic patient; report of a rare case.

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    Mohammad Jafarian

    2013-12-01

    Full Text Available Isolated impacted supernumerary teeth are quite rare, but they can be seen associated with several syndromes such as cleidocranial dysostosis or Gardner's syndrome. This article aims to discuss a case of sequential formation of supernumerary teeth with no other associated disease or syndrome. A 17-year-old Iranian male with 8 impacted supernumerary teeth was referred to the department of pediatric dental clinic at Shahid Beheshti Medical University in Tehran with a history of several impacted unerupted teeth. Repeated and periodical clinical and radiographic examinations revealed newly formed teeth buds in unusual dental ages. All extra teeth were associated with generalized enamel hypoplasia to some degree on their relative permanent adjacent teeth. The patient did not have any record of a systemic disease or any syndromic condition to relate his dental problem to. This rare condition involved repeated and continued formation of extra teeth out of the normal numbers and dental age evident in serial radiographs.

  7. Use of a Piezosurgery Technique to Remove a Deeply Impacted Supernumerary Tooth in the Anterior Maxilla

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    Shintaro Sukegawa

    2015-01-01

    Full Text Available Deeply impacted supernumerary teeth in the anterior maxillary cannot be generally removed by the conventional labial or palatal surgical approach because of the risk of damaging the surrounding soft tissues and the possibility of injuring the roots of adjacent permanent teeth. In piezosurgery, bony tissues are selectively cut, thereby avoiding the soft tissue damage caused by rotary cutting instruments. We report the case of a 15-year-old Japanese boy from whom a deeply impacted supernumerary tooth in the anterior maxillary was safely removed through the floor of the nasal cavity. The surgical extraction was performed without damaging the nasal mucosa or adjacent structures such as the roots of the adjacent permanent teeth. Considering that piezosurgery limits the extent of surgical invasion, this technique can be practiced as a minimally invasive and safe surgical procedure for treating suitably selected cases with a deeply impacted supernumerary tooth.

  8. Management of Delayed Eruption of Permanent Maxillary Incisor associated with the Presence of Supernumerary Teeth: A Case Report

    Science.gov (United States)

    Nagpal, Rajni; Singh, Mousumi; Chaudhary, Seema

    2011-01-01

    A supernumerary tooth is one that is additional to the normal series and can be found in almost any region of the dental arch. Clinically, supernumerary teeth are able to cause different local disorders. It is important for the dentist to be aware of the clinical complications of supernumerary teeth, the most common being the delayed eruption of permanent teeth. Early diagnosis and management of supernumerary teeth is important to prevent the need for more complex surgical and orthodontic treatment. This case report highlights the problem of delayed eruption of permanent maxillary left central incisor in a 9-year-old boy due to two supernumerary teeth, one tuberculate type and other impacted inverted mesiodens. PMID:27678238

  9. The dynamics of supernumerary tooth development are differentially regulated by Sprouty genes.

    Science.gov (United States)

    Lagronova-Churava, Svatava; Spoutil, Frantisek; Vojtechova, Simona; Lesot, Herve; Peterka, Miroslav; Klein, Ophir D; Peterkova, Renata

    2013-07-01

    In mice, a toothless diastema separates the single incisor from the three molars in each dental quadrant. In the prospective diastema of the embryo, small rudimentary buds are found that are presumed to be rudiments of suppressed teeth. A supernumerary tooth occurs in the diastema of adult mice carrying mutations in either Spry2 or Spry4. In the case of Spry2 mutants, the origin of the supernumerary tooth involves the revitalization of a rudimentary tooth bud (called R2), whereas its origin in the Spry4 mutants is not known. In addition to R2, another rudimentary primordium (called MS) arises more anteriorly in the prospective diastema. We investigated the participation of both rudiments (MS and R2) in supernumerary tooth development in Spry2 and Spry4 mutants by comparing morphogenesis, proliferation, apoptosis, size and Shh expression in the dental epithelium of MS and R2 rudiments. Increased proliferation and decreased apoptosis were found in MS and R2 at embryonic day (ED) 12.5 and 13.5 in Spry2(-/-) embryos. Apoptosis was also decreased in both rudiments in Spry4(-/-) embryos, but the proliferation was lower (similar to WT mice), and supernumerary tooth development was accelerated, exhibiting a cap stage by ED13.5. Compared to Spry2(-/-) mice, a high number of Spry4(-/-) supernumerary tooth primordia degenerated after ED13.5, resulting in a low percentage of supernumerary teeth in adults. We propose that Sprouty genes were implicated during evolution in reduction of the cheek teeth in Muridae, and their deletion can reveal ancestral stages of murine dental evolution. Copyright © 2013 Wiley Periodicals, Inc.

  10. An epidemiological study on supernumerary teeth: a survey on 5,000 people.

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    Kumar, Dara Kalyan; Gopal, K Saraswathy

    2013-07-01

    The formation of dental tissues is a highly delicate and complex phenomenon. Any alteration in this process leads to various dental anomalies which affect the tooth number, size, shape and structure. Supernumerary teeth are one such anomaly which affects the tooth number. Supernumerary teeth can give rise to various complications and pathologies or they may have a familial / syndromic association. They may occur along with other dental anomalies. Thus, such teeth have a definite clinical significance. The aim of the following study was to know the prevalence of the supernumerary teeth and the distribution of the cases according to the age, sex, jaw, region, eruption status, and the position. A total of 5000 patients were examined for a period of 1 year's duration and they were divided into different groups. Group I consisted of individuals who were aged between 5-20 years, Group II consisted of individuals who were aged between 21-40 years, and Group III consisted of individuals who were aged 41 years and above. The dental examination was conducted by using a mouth mirror and a probe, to determine the presence of supernumerary teeth. All the cases with supernumerary teeth were further observed and the details were recorded in a prepared porforma. These cases were also subjected to general physical examinations (to rule out any syndromes) and radiographic examinations. Photographs were also made. Although supernumerary teeth is an unusual anomaly, it is not as rare as was previously reported. The identification of this anomaly could provide a hint towards the possibility of complications, pathologies, other dental anomalies, syndromes and a familial association.

  11. Endodontic management of a supernumerary tooth fused to the maxillary permanent lateral Incisor

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    Avinash A Patil

    2014-01-01

    Full Text Available The aim of this case report is to present the endodontic management of a supernumerary tooth fused to the maxillary left lateral incisor. Such anomalies pose a challenge even to the most experienced clinician in treating these teeth. This report described a case of 21-year-old male patient with a classic case of complete fusion of maxillary left lateral incisor and a supernumerary tooth. A modified access preparation was made and two separate root canal orifices were identified. Both root canal systems were prepared separately and obturated efficiently until accepted lengths. This reported case highlights the importance of clinical and radiographic correlation in arriving to a definitive diagnosis.

  12. Unusual Case of a Talon Cusp on a Supernumerary Tooth in Association with a Mesiodens

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    Prashant Babaji

    2010-06-01

    Full Text Available Talon cusp is an accessory cusp similar to a projection, extending from the cingulum or cemento-enamel junction to the incisal edge. It occurs on labial or palatal surfaces of primary or permanent anterior teeth in both arches. This accessory cusp can occur as an isolated entity or in association with other dental anomalies. Occurrence of a talon cusp on supernumerary teeth is rare and uncommon. This paper reports an unusual case of a talon cusp on a supernumerary tooth in association with mesiodens.

  13. Hypohyperdontia: Agenesis of three third molars and mandibular centrals associated with midline supernumerary tooth in mandible

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    Sivakumar Nuvvula

    2010-01-01

    Full Text Available Agenesis of teeth in a patient who also presents with a supernumerary tooth is one of the rare numerical anomalies in human dentition. Agenesis of third molars was shown to be associated with other missing permanent teeth. A review of literature on hypodontia including third molar agenesis, hyperdontia and a concomitant presence of these two conditions which is termed as hypohyperdontia is presented along with a case showing agenesis of three third molars, both mandibular central incisors and a midline supernumerary tooth.

  14. Dentigerous cyst associated with ectopic canine and a supernumerary tooth: a rare occurrence.

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    Ramakrishna, Ashwini; Lambade, Pravin

    2013-07-01

    Amongst the cysts of the jaw dentigerous cyst (DC) is one of the most prevalent types of odontogenic cysts, which is associated with the crown of an unerupted or developing tooth. DC is more commonly seen with mandibular third molar and maxillary canine and rarely other teeth are involved. These cysts seldom associate with supernumerary teeth. The purpose of this article is to describe a case of large dentigerous cyst associated with supernumerary teeth and an ectopic canine, which is a rare presentation along with its management.

  15. Diagnosis and Management of Supernumerary (Mesiodens: A Review of the Literature

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    G. Meighani

    2010-03-01

    Full Text Available Supernumerary tooth is one of the developmental problems in children. Mesiodens is a supernumerary tooth present in the midline between the two central incisors. It usually results in oral problems such as malocclusion, food impaction, poor aesthetics, and cyst formation. The prevalence of mesiodens varies between 0.09% and 2.05% in different studies.This paper reviews current literature on etiology, prevalence, diagnosis, and management of this problem. Accordingly, early diagnosis and treatment is suggested to preventorthodontic and pathologic complications.

  16. Unusual case of a talon cusp on a supernumerary tooth in association with a mesiodens.

    Science.gov (United States)

    Babaji, Prashant; Sanadi, Firoza; Melkundi, Mahesh

    2010-01-01

    Talon cusp is an accessory cusp similar to a projection, extending from the cingulum or cemento-enamel junction to the incisal edge. It occurs on labial or palatal surfaces of primary or permanent anterior teeth in both arches. This accessory cusp can occur as an isolated entity or in association with other dental anomalies. Occurrence of a talon cusp on supernu-merary teeth is rare and uncommon. This paper reports an unusual case of a talon cusp on a supernumerary tooth in association with mesiodens.

  17. Transcellular degradation of axonal mitochondria.

    Science.gov (United States)

    Davis, Chung-ha O; Kim, Keun-Young; Bushong, Eric A; Mills, Elizabeth A; Boassa, Daniela; Shih, Tiffany; Kinebuchi, Mira; Phan, Sebastien; Zhou, Yi; Bihlmeyer, Nathan A; Nguyen, Judy V; Jin, Yunju; Ellisman, Mark H; Marsh-Armstrong, Nicholas

    2014-07-01

    It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through formation of large protrusions that originate from otherwise healthy axons. A virally introduced tandem fluorophore protein reporter of acidified mitochondria reveals that acidified axonal mitochondria originating from the retinal ganglion cell are associated with lysosomes within columns of astrocytes in the ONH. According to this reporter, a greater proportion of retinal ganglion cell mitochondria are degraded at the ONH than in the ganglion cell soma. Consistently, analyses of degrading DNA reveal extensive mtDNA degradation within the optic nerve astrocytes, some of which comes from retinal ganglion cell axons. Together, these results demonstrate that surprisingly large proportions of retinal ganglion cell axonal mitochondria are normally degraded by the astrocytes of the ONH. This transcellular degradation of mitochondria, or transmitophagy, likely occurs elsewhere in the CNS, because structurally similar accumulations of degrading mitochondria are also found along neurites in superficial layers of the cerebral cortex. Thus, the general assumption that neurons or other cells necessarily degrade their own mitochondria should be reconsidered.

  18. Centromere activity in dicentric small supernumerary marker chromosomes.

    Science.gov (United States)

    Ewers, Elisabeth; Yoda, Kinya; Hamid, Ahmed B; Weise, Anja; Manvelyan, Marina; Liehr, Thomas

    2010-07-01

    Twenty-five dicentric small supernumerary marker chromosomes (sSMC) derived from #13/21, #14, #15, #18, and #22 were studied by immunohistochemistry for their centromeric activity. Centromere protein (CENP)-B was applied as marker for all centromeres and CENP-C to label the active ones. Three different 'predominant' activation patterns could be observed, i.e., centric fusion or either only one or all two centromeres were active. In one inherited case, the same activation pattern was found in mother and son. In acrocentric-derived sSMC, all three activation patterns could be present. In contrary, in chromosome 18-derived sSMC, only the fusion type was observed. In concordance with previous studies a certain centromeric plasticity was observed in up to 13% of the cells of an individual case. Surprisingly, the obtained data suggests a possible influence of the sSMC carrier's gender on the implementation of the predominant activation pattern; especially, only one active centromere was found more frequently in female than in male carriers. Also, it might be suggested that dicentric sSMC with one active centromere could be less stable than such with two active ones-centromeric plasticity might have an influence here, as well. Also, centromere activity in acrocentric-derived dicentrics could be influenced by heteromorphisms of the corresponding short arms. Finally, evidence is provided that the closer the centromeres of a dicentric are and if they are not fused, the more likely it was that both of them became active. In concordance and refinement with previous studies, a distance of 1.4 Mb up to about 13 Mb the two active centromere state was favored, while centromeric distance of over approximately 15 Mb lead to inactivation of one centromere. Overall, here, the first and largest ever undertaken study in dicentric sSMC is presented, providing evidence that the centromeric activation pattern is, and parental origin may be of interest for their biology. Influence of

  19. Clinical management of a fused upper premolar with supernumerary tooth: a case report

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    Kyu-Min Cho

    2014-11-01

    Full Text Available n dentistry, the term 'fusion' is used to describe a developmental disorder of dental hard tissues. In the permanent dentition, fusion of a normal tooth and a supernumerary tooth usually involves the incisors or canines. However, a few cases of fusion involving premolars have also been reported to date. We present a rare case in which fusion of the maxillary left second premolar and a supernumerary tooth in a 13-year-old girl was diagnosed using cone beam computed tomography (CBCT, Alphard-3030, Asahi Roentgen Ind. Co., Ltd.. The tooth was bicuspidized after routine nonsurgical root canal treatment, and the separated teeth underwent appropriate restoration procedures. The second premolar and supernumerary tooth remained asymptomatic without any signs of inflammation after a follow-up period of 9 years. Identification of anatomical anomalies is important for treatment in cases involving fusion with supernumerary tooth, and therefore the microscopic examinations and CBCT are essential for the diagnosis. Fused teeth can be effectively managed by the comprehensive treatment which includes both endodontic and periodontal procedures.

  20. Lateral incisor agenesis, canine impaction and characteristics of supernumerary teeth in a South European male population

    NARCIS (Netherlands)

    Delli, Konstantina; Livas, Christos; Bornstein, Michael M

    2013-01-01

    OBJECTIVE: To assess the prevalence of lateral incisor agenesis impacted canines and supernumerary teeth in a young adult male population. MATERIALS AND METHODS: The panoramic radiographs of 1745 military students (mean age: 18.6 ± 0.52 years) who attended the Center of Aviation Medicine of the Arme

  1. Multiple crown size variables of the upper incisors in patients with supernumerary teeth compared with controls

    NARCIS (Netherlands)

    Khalaf, K.; Smith, R. N.; Elcock, C.; Brook, A. H.

    2009-01-01

    Aims: As part of ongoing studies of the aetiology of dental anomalies the aims of this study were to identify multiple components of tooth size of the upper permanent incisors in 34 patients with supernumerary teeth and to compare them with those in a control group to determine whether the presence

  2. Lateral incisor agenesis, canine impaction and characteristics of supernumerary teeth in a South European male population

    NARCIS (Netherlands)

    Delli, Konstantina; Livas, Christos; Bornstein, Michael M

    2013-01-01

    OBJECTIVE: To assess the prevalence of lateral incisor agenesis impacted canines and supernumerary teeth in a young adult male population. MATERIALS AND METHODS: The panoramic radiographs of 1745 military students (mean age: 18.6 ± 0.52 years) who attended the Center of Aviation Medicine of the Arme

  3. Multidisciplinary management of impacted central incisors due to supernumerary teeth and an associated dentigerous cyst

    Directory of Open Access Journals (Sweden)

    Ritesh R Kalaskar

    2011-01-01

    Full Text Available Supernumerary teeth are the most common developmental dental anomaly resulting from hyperactivity of dental lamina, dichotomy, environmental factor, or polygenetic process of atavism. Supernumerary teeth present classical oral complication such as impaction of adjacent teeth, crowding, diastema formation, rotation, displacement of teeth, and occlusal interference. A dentigerous cyst associated with anterior supernumerary teeth (mesiodens is rare and accounts for 5% of all dentigerous cysts. The present case reports describe the successful management of the impacted permanent maxillary central incisor positioned high in the vestibule. A combination of surgical and orthodontic techniques was employed to improve treatment outcome with greater hard and soft tissue preservation and to prevent psychological problems. In the surgical phase, supernumerary teeth and dentigerous cyst were removed. Subsequently traction was employed by bonding bracket on the labial surface using closed and open eruption techniques. Successively, fixed orthodontic treatment was started to align permanent maxillary central incisors in an occlusal plane. Thus, combination of surgical and orthodontic method can be the treatment of choice over surgical extraction, implant placement, and surgical repositioning.

  4. [Diagnosis and treatment of supernumerary teeth in the premaxillary region: a literature review].

    Science.gov (United States)

    Ratson, T

    2013-01-01

    Supernumerary teeth are more frequently located in the premaxillary region. Mesiodentes are the most common supernumerary teeth, occurring in 0.15% to 1.9% of the population. Supernumerary teeth are frequently diagnosed in a random radiograph, or after clinical symptoms appear. The majority of the complications consist of delayed or ectopic eruption of the permanent incisors. It is important for the clinician to be aware of the phenomenon and its implications, in order to diagnose it as early as possible. Extraction of the supernumerary teeth in the late mixed dentition, will minimize the chances of damaging the adjacent permanent teeth, but will reduce the possibility of spontaneous eruption of an impacted permanent incisor. Extraction in the early mixed dentition can expedite the eruption of the permanent incisor, although it may involve sedation or general anesthesia, due to lack of cooperation in the young patient. Because to the risk of uneruption of the permanent impacted incisor, exposure of the teeth and bonding a ligature or bracket at the same procedure, and providing a possibility for the dentist to make the incisor erupt after the first operation, should the incisor not erupt spontaneously. Treating these cases require the cooperation of pediatric dentist, orthodontic and dental surgeon, and sometimes the involvement of an anesthesiologist.

  5. Nonsyndromic Bilateral Multiple Impacted Supernumerary Mandibular Third Molars: A Rare and Unusual Case Report

    Directory of Open Access Journals (Sweden)

    G. Siva Prasad Reddy

    2013-01-01

    Full Text Available A supernumerary tooth is that which is present additionally to the normal series and can be found in any region of the dental arch. An impacted tooth is defined as the one which is embedded in the alveolus, so that its eruption is prevented, or the tooth is locked in position by bone or the adjacent teeth. The occurrence of multiple supernumerary teeth in only one patient in the absence of an associated systemic condition or syndrome is considered as a rare phenomenon. The occurrence of supernumerary teeth in the lower molar region is rare. A prevalence of less than 2% of cases occurring in this region has been estimated. Their occurrence presents a clinical problem for orthodontists and oral surgeons. The cause, frequency, complications, and surgical operation of impacted teeth are always interesting subjects for study and research. An impacted tooth can result in caries, pulp disease, periapical and periodontal disease, temporomandibular joint disorder, infection of the fascial space, root resorption of the adjacent tooth, and even oral and maxillofacial tumours. The management of impacted wisdom teeth has changed over the past 20 years from removal of nonsymptomatic third molars to simple observation. The aim of this paper is to present a rare case of bilateral multiple impacted supernumerary mandibular third molars.

  6. Hemangioendothelioma of bone in a patient with a constitutional supernumerary marker

    DEFF Research Database (Denmark)

    Rogatto, S R; Rainho, C A; Zhang, Z M

    1999-01-01

    A 13-year old girl was diagnosed as having a bone hemangioendothelioma. Cytogenetic studies identified the presence of a small supernumerary marker chromosome in this patient. Classical cytogenetic methods using G-, C-, Ag-NOR-banding were supplemented by spectral karyotyping (SKY) and fluorescen...

  7. Multidisciplinary management of impacted central incisors due to supernumerary teeth and an associated dentigerous cyst

    Science.gov (United States)

    Kalaskar, Ritesh R.; Kalaskar, Ashita R.

    2011-01-01

    Supernumerary teeth are the most common developmental dental anomaly resulting from hyperactivity of dental lamina, dichotomy, environmental factor, or polygenetic process of atavism. Supernumerary teeth present classical oral complication such as impaction of adjacent teeth, crowding, diastema formation, rotation, displacement of teeth, and occlusal interference. A dentigerous cyst associated with anterior supernumerary teeth (mesiodens) is rare and accounts for 5% of all dentigerous cysts. The present case reports describe the successful management of the impacted permanent maxillary central incisor positioned high in the vestibule. A combination of surgical and orthodontic techniques was employed to improve treatment outcome with greater hard and soft tissue preservation and to prevent psychological problems. In the surgical phase, supernumerary teeth and dentigerous cyst were removed. Subsequently traction was employed by bonding bracket on the labial surface using closed and open eruption techniques. Successively, fixed orthodontic treatment was started to align permanent maxillary central incisors in an occlusal plane. Thus, combination of surgical and orthodontic method can be the treatment of choice over surgical extraction, implant placement, and surgical repositioning. PMID:22114457

  8. Genome-wide genetic dissection of supernumerary spikelet and related traits in common wheat

    Science.gov (United States)

    Branched spike or supernumerary spikelet (SS) is a naturally occurring variant in wheat and holds great potential for increasing the number of grains per spike, and ultimately, increasing wheat yield. However, detailed knowledge of the molecular basis of spike branching in common wheat is lacking. I...

  9. Axon density and axon orientation dispersion in children born preterm

    NARCIS (Netherlands)

    Kelly, Claire E.; Thompson, Deanne K.; Chen, Jian; Leemans, Alexander; Adamson, Christopher L.; Inder, Terrie E.; Cheong, Jeanie L Y; Doyle, Lex W.; Anderson, Peter J.

    2016-01-01

    Background Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density

  10. The genome of Nectria haematococca: contribution of supernumerary chromosomes to gene expansion

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, J.J.; Rounsley, S.D.; Rodriguez-Carres, M.; Kuo, A.; Wasmann, C.c.; Grimwood, J.; Schmutz, J.; Taga, M.; White, G.J.; Zhuo, S.; Schwartz, D.C.; Freitag, M.; Ma, L.-J.; Danchin, E.G.J.; Henrissat, B.; Cutinho, P.M.; Nelson, D.R.; Straney, D.; Napoli, C.A.; Baker, B.M.; Gribskov, M.; Rep, M.; Kroken, S.; Molnar, I.; Rensing, C.; Kennell, J.C.; Zamora, J.; Farman, M.L.; Selker, E.U.; Salamov, A.; Shapiro, H.; Pangilinan, J.; Lindquist, E.; Lamers, C.; Grigoriev, I.V.; Geiser, D.M.; Covert, S.F.; Temporini, S.; VanEtten, H.D.

    2009-04-20

    The ascomycetous fungus Nectria haematococca, (asexual name Fusarium solani), is a member of a group of .50 species known as the"Fusarium solani species complex". Members of this complex have diverse biological properties including the ability to cause disease on .100 genera of plants and opportunistic infections in humans. The current research analyzed the most extensively studied member of this complex, N. haematococca mating population VI (MPVI). Several genes controlling the ability of individual isolates of this species to colonize specific habitats are located on supernumerary chromosomes. Optical mapping revealed that the sequenced isolate has 17 chromosomes ranging from 530 kb to 6.52 Mb and that the physical size of the genome, 54.43 Mb, and the number of predicted genes, 15,707, are among the largest reported for ascomycetes. Two classes of genes have contributed to gene expansion: specific genes that are not found in other fungi including its closest sequenced relative, Fusarium graminearum; and genes that commonly occur as single copies in other fungi but are present as multiple copies in N. haematococca MPVI. Some of these additional genes appear to have resulted from gene duplication events, while others may have been acquired through horizontal gene transfer. The supernumerary nature of three chromosomes, 14, 15, and 17, was confirmed by their absence in pulsed field gel electrophoresis experiments of some isolates and by demonstrating that these isolates lacked chromosome-specific sequences found on the ends of these chromosomes. These supernumerary chromosomes contain more repeat sequences, are enriched in unique and duplicated genes, and have a lower G+C content in comparison to the other chromosomes. Although the origin(s) of the extra genes and the supernumerary chromosomes is not known, the gene expansion and its large genome size are consistent with this species' diverse range of habitats. Furthermore, the presence of unique genes on

  11. The genome of Nectria haematococca: contribution of supernumerary chromosomes to gene expansion.

    Directory of Open Access Journals (Sweden)

    Jeffrey J Coleman

    2009-08-01

    Full Text Available The ascomycetous fungus Nectria haematococca, (asexual name Fusarium solani, is a member of a group of >50 species known as the "Fusarium solani species complex". Members of this complex have diverse biological properties including the ability to cause disease on >100 genera of plants and opportunistic infections in humans. The current research analyzed the most extensively studied member of this complex, N. haematococca mating population VI (MPVI. Several genes controlling the ability of individual isolates of this species to colonize specific habitats are located on supernumerary chromosomes. Optical mapping revealed that the sequenced isolate has 17 chromosomes ranging from 530 kb to 6.52 Mb and that the physical size of the genome, 54.43 Mb, and the number of predicted genes, 15,707, are among the largest reported for ascomycetes. Two classes of genes have contributed to gene expansion: specific genes that are not found in other fungi including its closest sequenced relative, Fusarium graminearum; and genes that commonly occur as single copies in other fungi but are present as multiple copies in N. haematococca MPVI. Some of these additional genes appear to have resulted from gene duplication events, while others may have been acquired through horizontal gene transfer. The supernumerary nature of three chromosomes, 14, 15, and 17, was confirmed by their absence in pulsed field gel electrophoresis experiments of some isolates and by demonstrating that these isolates lacked chromosome-specific sequences found on the ends of these chromosomes. These supernumerary chromosomes contain more repeat sequences, are enriched in unique and duplicated genes, and have a lower G+C content in comparison to the other chromosomes. Although the origin(s of the extra genes and the supernumerary chromosomes is not known, the gene expansion and its large genome size are consistent with this species' diverse range of habitats. Furthermore, the presence of unique

  12. Action-potential modulation during axonal conduction.

    Science.gov (United States)

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2011-02-04

    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  13. Optofluidic control of axonal guidance

    Science.gov (United States)

    Gu, Ling; Ordonez, Simon; Black, Bryan; Mohanty, Samarendra K.

    2013-03-01

    Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

  14. Surgical management of impacted incisors in associate with supernumerary teeth: A combine case report of spontaneous eruption and orthodontic extrusion

    Directory of Open Access Journals (Sweden)

    D Das

    2012-01-01

    Full Text Available Maxillary permanent incisors impaction is not a frequent case in dental practice, but its treatment is challenging because of its importance to facial esthetics. Supernumerary teeth are the main cause of impaction of upper incisors. Supernumerary teeth when present can cause both esthetic and pathologic problems. Early detection of such teeth is most important if complications are to be avoided. In this reported case, the orthopantamogram of a 9-year-old boy revealed two impacted supernumerary teeth in the maxillary anterior region, which was interfering with the eruption of the permanent central incisors. The impacted supernumerary teeth were surgically removed, 11 was repositioned in the arch as it was situated very high in the arch, close to the nasal floor. Twenty-one erupted spontaneously but orthodontic force was applied over 11 to bring it into the occlusion and alignment was achieved with 0.014 mm NiTi wire.

  15. Human intraretinal myelination: Axon diameters and axon/myelin thickness ratios

    Directory of Open Access Journals (Sweden)

    Thomas FitzGibbon

    2013-01-01

    Full Text Available Purpose: Human intraretinal myelination of ganglion cell axons occurs in about 1% of the population. We examined myelin thickness and axon diameter in human retinal specimens containing myelinated retinal ganglion cell axons. Materials and Methods: Two eyes containing myelinated patches were prepared for electron microscopy. Two areas were examined in one retina and five in the second retina. Measurements were compared to normal retinal and optic nerve samples and the rabbit retina, which normally contains myelinated axons. Measurements were made using a graphics tablet. Results: Mean axon diameter of myelinated axons at all locations were significantly larger than unmyelinated axons (P ≤ 0.01. Myelinated axons within the patches were significantly larger than axons within the optic nerve (P < 0.01. The relationship between axon diameter/fiber diameter (the G-ratio seen in the retinal sites differed from that in the nerve. G-ratios were higher and myelin thickness was positively correlated to axon diameter (P < 0.01 in the retina but negatively correlated to axon diameter in the nerve (P < 0.001. Conclusion: Intraretinally myelinated axons are larger than non-myelinated axons from the same population and suggests that glial cells can induce diameter changes in retinal axons that are not normally myelinated. This effect is more dramatic on intraretinal axons compared with the normal transition zone as axons enter the optic nerve and these changes are abnormal. Whether intraretinal myelin alters axonal conduction velocity or blocks axonal conduction remains to be clarified and these issues may have different clinical outcomes.

  16. Notch Signaling Inhibits Axon Regeneration

    OpenAIRE

    Bejjani, Rachid El; Hammarlund, Marc

    2012-01-01

    Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian CNS do not regenerate, and even neurons in the PNS often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neuron...

  17. Pallister-Killian syndrome caused by mosaicism for a supernumerary ring chromosome 12p.

    Science.gov (United States)

    Yeung, Alison; Francis, David; Giouzeppos, Olivia; Amor, David J

    2009-03-01

    Pallister-Killian syndrome (PKS) is a rare but distinctive chromosomal syndrome distinguished by severe intellectual impairment, characteristic facial features, and variable structural anomalies. The characteristic cytogenetic abnormality in PKS is a supernumerary isochromosome 12p that confers mosaic tetrasomy. We describe a female child with PKS in whom tetrasomy 12p resulted from a supernumerary ring chromosome containing two copies of chromosome 12cen --> p13, a novel cytogenetic finding. The ring chromosome exhibited tissue-limited mosaicism, being absent in blood but detected in 38% of buccal mucosa cells and 41% of skin fibroblasts. Our patient demonstrated the typical dysmorphic characteristics of PKS, but her development was relatively advanced in comparison to children with isochromosome PKS. Her milder developmental phenotype may be attributable to differences in the mosaic distribution or the genomic content of the ring chromosome compared to mosaic isochromosome 12p.

  18. Expansion of the Rib Head: A Novel Computed Tomographic Feature of Supernumerary Intrathoracic Ribs.

    Science.gov (United States)

    Kabakus, Ismail Mikdat; Atceken, Zeynep; Ariyurek, Orhan Macit

    2017-02-01

    Intrathoracic ribs are very rare congenital anomalies. Approximately 50 cases have been reported in the literature till date. They are usually present on the right side, between the third and eighth ribs without sex predominance. They may originate from a vertebral body or the proximal or distal part of a rib. In most cases, they are asymptomatic, but they may be associated with developmental abnormalities of ribs and vertebrae. The diagnosis is important to prevent further investigation or intervention. Here we present two rare cases with supernumerary intrathoracic rib and describe a novel sign, namely expansion of the rib head. To the best of our knowledge, this is the shortest supernumerary intrathoracic rib, reported in the literature, on the left side originating from the head of the second rib, which could have been misdiagnosed as osteochondroma due to its atypical features.

  19. Supernumerary Nipples, Congenital Scoliosis, Spina Bifida, Diastematomyelia, and Crossed Renal Ectopia in a child

    Directory of Open Access Journals (Sweden)

    Kiran Panthee

    2016-11-01

    Full Text Available Introduction: Supernumerary nipples are common anomalies which may be associated with several systemic disorders, particularly urinary tract abnormalities.   Case report: Here we report a case of a 4½ year old male presenting to the pediatric out patient clinic with fever for three days and recurrent sinopulmonary infections. The child had supernumerary nipples over the right side with deformed thoracic cage, congenital scoliosis, diastematomyelia, crossed renal ectopia, and spina bifida. All the conditions present together did not match any syndrome reported till date.   Conclusion: This was a rare syndrome and did not match fully with any known syndromes till date. This case warranted further investigation for its definite diagnosis but we do not have resources to that extent.

  20. Recurrent epistaxis caused by an intranasal supernumerary tooth in a young adult

    OpenAIRE

    Al Dhafeeri, Hamed O.; Kavarodi, Abdulmajid; Shaikh, Khalil Al; Bukhari, Ahmed; Hussain, Omair Al; Baramawy, Ahmed El

    2014-01-01

    Patient: Male, 27 Final Diagnosis: Recurrent epistaxis Symptoms: Nasal bleeding Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Congenital defects/diseases Background: Recurrent epistaxis is a common disorder among children and young adults. We report an unusual cause, intranasal supernumerary tooth causing friction with Little’s area of the nasal septum. Case Report: A 22-year-old male presented with recurrent, mild, unilateral left-sided epistaxis once t...

  1. Bilateral fusion of mandibular second molars with supernumerary teeth: case report

    Directory of Open Access Journals (Sweden)

    Nunes Eduardo

    2002-01-01

    Full Text Available Fusion is a developmental anomaly characterized by the union of two adjacent teeth. In this article we report a rare case of bilateral fusion of permanent mandibular second molars with supernumerary teeth. The rarity with which this entity appears, along with its complex characteristics, often make it difficult to treat. The endodontic management of one tooth is described, as well as the successful treatment of a periradicular lesion.

  2. Mosaic small supernumerary marker chromosome 1 at amniocentesis: prenatal diagnosis, molecular genetic analysis and literature review.

    Science.gov (United States)

    Chen, Chih-Ping; Chen, Ming; Su, Yi-Ning; Huang, Jian-Pei; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Chang, Shun-Ping; Chen, Yu-Ting; Lee, Chen-Chi; Chen, Li-Feng; Pan, Chen-Wen; Wang, Wayseen

    2013-10-15

    We present prenatal diagnosis and molecular cytogenetic analysis of mosaic small supernumerary marker chromosome 1 [sSMC(1)]. We review the literature of sSMC(1) at amniocentesis and chromosome 1p21.1-p12 duplication syndrome. We discuss the genotype-phenotype correlation of the involved genes of ALX3, RBM15, NTNG1, SLC25A24, GPSM2, TBX15 and NOTCH2 in this case.

  3. Existence of inelastic supernumerary nuclear rainbow in 16O+12C scattering

    Science.gov (United States)

    Ohkubo, S.; Hirabayashi, Y.; Ogloblin, A. A.

    2017-08-01

    The existence of a supernumerary nuclear rainbow in inelastic scattering is reported. This is done by studying inelastic 16O scattering from 12C, exciting the 2+ (4.44 MeV) state of 12C and elastic scattering at the incident energies in the range 124-200 MeV, using the coupled channels method. An extended double folding potential is used. This is derived from realistic wave functions for 12C and 16O calculated with a microscopic α cluster model and a finite-range density-dependent nucleon-nucleon force. Excitations to the 2+ (4.44 MeV), 3- (9.64 MeV), and 4+ (14.08 MeV) states of 12C, and the 3- (6.13 MeV) and 2+ (6.92 MeV) states of 16O are included in the coupled channels calculations. The emergence of the supernumerary bow is understood by the properties of both the Luneburg-lens-like potential in the internal region and diffuse attraction in the outer region. The existence of a supernumerary rainbow for inelastic scattering in addition to the existence of a dynamically created secondary rainbow and a dynamically refracted primary rainbow for elastic scattering, which are not observed in meteorological rainbows, further deepens the understanding of nuclear rainbows.

  4. Under your nose: a rare finding during dissection provides insights into maxillary supernumerary teeth.

    Science.gov (United States)

    Redwood, C; Townsend, G C; Ghabriel, M; Brook, A H

    2014-09-01

    A supernumerary tooth was found during anatomical dissection. The position of this tooth, still impacted in the maxilla, and the associated pathology make this a rare case. During dissection by dental students of the sagittally-sectioned head of a cadaver, a supernumerary tooth was identified in the mid-palatal area. Further dissection revealed a swelling with a thin bony covering related to the crown of the tooth. The maxilla was removed en bloc and radiographic examination, CT scanning, electron microscopy and histology were undertaken. The tooth had a crenulated occlusal surface and a single root. It was 25 mm posterior to the root apex of the permanent upper central incisor. The swelling, confirmed by radiographs and CT imaging to be associated with the crown, occupied approximately one-third of the maxillary sinus. The 3D shape of the cystic lesion was visualized by a composite digital movie. The crown form, position of the tooth and the associated dentigerous cyst suggested it was a palatally developing supernumerary premolar which had been displaced to the palatal midline by the expanding cyst. This rare case highlights the learning and teaching opportunities available during dissection, showing important variations in both development and clinical anatomy. © 2014 Australian Dental Association.

  5. The Multidisciplinary Management of Fused Maxillary Lateral Incisor with a Supernumerary Tooth in Cleft Lip Adolescence

    Directory of Open Access Journals (Sweden)

    Ahmet Yagci

    2014-01-01

    Full Text Available Fusion, an uncommon anomaly of the hard dental tissues, is potentially the cause of clinical problems related to esthetics, tooth spacing, and other periodontal complications. This paper describes a multidisciplinary approach involving surgical, endodontic, restorative, and orthodontic attention for the successful, functional, and esthetic rehabilitation of a maxillary left lateral incisor fused with a supernumerary tooth in unilateral cleft lip adolescence in contralateral side. After clinical and radiographic examinations, a fusion between the left maxillary lateral incisor and a supernumerary tooth was diagnosed in the patient, and a small connection was detected between the pulp systems of the two root canals. The case reported in this paper presents the successful resolution of a fused maxillary lateral incisor with a supernumerary tooth, using endodontic, surgical, restorative, and orthodontic management. The decision made in extracting or retaining the fused tooth depends on the arch discrepancy and esthetic needs. Future studies, with long-term followup, will be helpful in evaluating the long-term efficacy of the different treatment options.

  6. Human Genetic Disorders of Axon Guidance

    Science.gov (United States)

    Engle, Elizabeth C.

    2010-01-01

    This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders. PMID:20300212

  7. AxonSeg: Open Source Software for Axon and Myelin Segmentation and Morphometric Analysis.

    Science.gov (United States)

    Zaimi, Aldo; Duval, Tanguy; Gasecka, Alicja; Côté, Daniel; Stikov, Nikola; Cohen-Adad, Julien

    2016-01-01

    Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy (SEM) only). Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLAB-based graphical user interface (GUI) and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i) image pre-processing; (ii) pre-segmentation of axons over a cropped image and discriminant analysis (DA) to select the best parameters based on axon shape and intensity information; (iii) automatic axon and myelin segmentation over the full image; and (iv) atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM), SEM and coherent anti-Stokes Raman scattering (CARS) microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology. AxonSeg is open source and freely available at: https://github.com/neuropoly/axonseg.

  8. AxonSeg: open source software for axon and myelin segmentation and morphometric analysis

    Directory of Open Access Journals (Sweden)

    Aldo Zaimi

    2016-08-01

    Full Text Available Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy only. Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLAB-based graphical user interface and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i image pre-processing, (ii pre-segmentation of axons over a cropped image and discriminant analysis to select the best parameters based on axon shape and intensity information, (iii automatic axon and myelin segmentation over the full image and (iv atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM, scanning electron microscopy (SEM and coherent anti-Stokes Raman scattering (CARS microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology. AxonSeg is open source and freely available at: https://github.com/neuropoly/axonseg.

  9. Prevalence of supernumerary teeth in permanent dentition among patients attending a dental college in South Kerala: A pilot study

    Directory of Open Access Journals (Sweden)

    Devi Gopakumar

    2014-01-01

    Full Text Available Background: Supernumerary teeth are excess number of teeth formed as a result of disturbances occurring during odontogenesis. The objective of the study was to investigate the prevalence of supernumerary teeth in permanent dentition among patients attending a dental college in South Kerala. Materials and Methods: In this study, 11,141 subjects attending the out-patient department of PMS College of Dental Science and Research, Thiruvananthapuram, Kerala were examined for supernumerary teeth like mesiodens, paramolars, distomolars, third premolars, second laterals, and odontomes during the period May 2012-May 2013. Ethical clearance was obtained from the institutional ethical committee for the study. Results: The study showed a prevalence of 0.39% and a sex distribution of M:F equal to 2:1. The incidence of supernumerary teeth found was as follows: mesiodens (0.14%, paramolars (0.13%, third premolar (0.04%, distomolar (0.03%, extralateral (0.02%, and odontome (0.03%. The male:female gender predilection was as follows: mesiodens (3:1, paramolars (1.3:1, third premolar (4:1, distomolar (1:2, and odontome (2:1. Conclusion: This study showed a 0.39% prevalence of supernumerary teeth in this population.

  10. Axonal interferon responses and alphaherpesvirus neuroinvasion

    Science.gov (United States)

    Song, Ren

    Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore

  11. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    , action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  12. Cable energy function of cortical axons.

    Science.gov (United States)

    Ju, Huiwen; Hines, Michael L; Yu, Yuguo

    2016-01-01

    Accurate estimation of action potential (AP)-related metabolic cost is essential for understanding energetic constraints on brain connections and signaling processes. Most previous energy estimates of the AP were obtained using the Na(+)-counting method, which seriously limits accurate assessment of metabolic cost of ionic currents that underlie AP conduction along the axon. Here, we first derive a full cable energy function for cortical axons based on classic Hodgkin-Huxley (HH) neuronal equations and then apply the cable energy function to precisely estimate the energy consumption of AP conduction along axons with different geometric shapes. Our analytical approach predicts an inhomogeneous distribution of metabolic cost along an axon with either uniformly or nonuniformly distributed ion channels. The results show that the Na(+)-counting method severely underestimates energy cost in the cable model by 20-70%. AP propagation along axons that differ in length may require over 15% more energy per unit of axon area than that required by a point model. However, actual energy cost can vary greatly depending on axonal branching complexity, ion channel density distributions, and AP conduction states. We also infer that the metabolic rate (i.e. energy consumption rate) of cortical axonal branches as a function of spatial volume exhibits a 3/4 power law relationship.

  13. Commissural axons of the mouse cochlear nucleus.

    Science.gov (United States)

    Brown, M Christian; Drottar, Marie; Benson, Thane E; Darrow, Keith

    2013-05-01

    The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorsoventral (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broadband inhibition observed in responses to contralateral sound, and they may balance input from the two ears with a quick time course.

  14. Axon reflexes in human cold exposed fingers

    NARCIS (Netherlands)

    Daanen, H.A.M.; Ducharme, M.B.

    2000-01-01

    Exposure of fingers to severe cold induces cold induced vasodilation (CIVD). The mechanism of CIVD is still debated. The original theory states that an axon reflex causes CIVD. To test this hypothesis, axon reflexes were evoked by electrical stimulation of the middle fingers of hands immersed in

  15. Axon reflexes in human cold exposed fingers

    NARCIS (Netherlands)

    Daanen, H.A.M.; Ducharme, M.B.

    2000-01-01

    Exposure of fingers to severe cold induces cold induced vasodilation (CIVD). The mechanism of CIVD is still debated. The original theory states that an axon reflex causes CIVD. To test this hypothesis, axon reflexes were evoked by electrical stimulation of the middle fingers of hands immersed in wat

  16. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  17. Dynamics of mitochondrial transport in axons

    Directory of Open Access Journals (Sweden)

    Robert Francis Niescier

    2016-05-01

    Full Text Available The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons.

  18. Early events in axon/dendrite polarization.

    Science.gov (United States)

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.

  19. Supernumerary, ectopic tooth in the maxillary antrum presenting with recurrent haemoptysis

    Directory of Open Access Journals (Sweden)

    Hameed Anam

    2010-11-01

    Full Text Available Abstract Background Ectopic eruption of teeth in non-dental sites is a rare phenomenon and can present in a variety of ways such as chronic or recurrent sinusitis, sepsis, nasolacrimal duct obstruction, headaches, ostiomeatal complex disease and facial numbness. However, presentation of such patients with recurrent haemoptysis has not been described in the literature so far. We have described a case of an ectopic, supernumerary molar tooth in the maxillary antrum in a patient who initially presented with haemoptysis. Case presentation A 45-year-old male presented with a 2-month history of episodic haemoptysis. A pedunculated growth from the inferior nasal turbinate was seen with fibre-optic visualization. Although the patient was empirically started on antibiotic and anti-allergic therapy, there was no improvement after a few weeks and the patient had recurrent episodes of haemoptysis. Fibre-optic visualization was repeated showing bilateral osteomeatal erythema. Computed tomography scan of the paranasal sinuses demonstrated complete opacification of the left maxillary antrum along with a focal area of density comparable to bone. An ectopic, supernumerary molar tooth was found in the left maxillary antrum on endoscopic examination and subsequently removed. In addition, copious purulent discharge was seen. Post-operatively, the patient was treated with a 10-day course of oral amoxicillin-clavulanate. On follow-up, he reported resolution of symptoms. Conclusion Recurrent haemoptysis has not been described as a presentation for a supernumerary, ectopic tooth in literature before. We recommend that in patients with sinusitis-type of opacification of maxillary antrum and whose condition is refractory to conventional medical treatment, consideration should be given to the investigation of possible underlying anomalies as the cause of such symptoms. Presence of foreign bodies and ectopic teeth in paranasal sinuses can be reliably excluded with the use

  20. Supernumerary, ectopic tooth in the maxillary antrum presenting with recurrent haemoptysis.

    Science.gov (United States)

    Saleem, Taimur; Khalid, Umair; Hameed, Anam; Ghaffar, Shehzad

    2010-11-11

    Ectopic eruption of teeth in non-dental sites is a rare phenomenon and can present in a variety of ways such as chronic or recurrent sinusitis, sepsis, nasolacrimal duct obstruction, headaches, ostiomeatal complex disease and facial numbness. However, presentation of such patients with recurrent haemoptysis has not been described in the literature so far. We have described a case of an ectopic, supernumerary molar tooth in the maxillary antrum in a patient who initially presented with haemoptysis. A 45-year-old male presented with a 2-month history of episodic haemoptysis. A pedunculated growth from the inferior nasal turbinate was seen with fibre-optic visualization. Although the patient was empirically started on antibiotic and anti-allergic therapy, there was no improvement after a few weeks and the patient had recurrent episodes of haemoptysis. Fibre-optic visualization was repeated showing bilateral osteomeatal erythema. Computed tomography scan of the paranasal sinuses demonstrated complete opacification of the left maxillary antrum along with a focal area of density comparable to bone. An ectopic, supernumerary molar tooth was found in the left maxillary antrum on endoscopic examination and subsequently removed. In addition, copious purulent discharge was seen. Post-operatively, the patient was treated with a 10-day course of oral amoxicillin-clavulanate. On follow-up, he reported resolution of symptoms. Recurrent haemoptysis has not been described as a presentation for a supernumerary, ectopic tooth in literature before. We recommend that in patients with sinusitis-type of opacification of maxillary antrum and whose condition is refractory to conventional medical treatment, consideration should be given to the investigation of possible underlying anomalies as the cause of such symptoms. Presence of foreign bodies and ectopic teeth in paranasal sinuses can be reliably excluded with the use of appropriate radiological imaging and endoscopic examination.

  1. Multiple bilateral supernumerary mandibular premolars in a non-syndromic patient with associated orthokeratised odontogenic cyst- A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Vikrant O Kasat

    2012-01-01

    Full Text Available Multiple supernumerary teeth are very rare, accounting for less than 1% of cases. They are commonly associated with syndromes like Gardner′s syndrome and cleidocranial dysostosis and cleft lip and palate. Non-syndromic multiple supernumerary teeth have a predilection to occur in the mandibular premolar region. Orthokeratinized odontogenic cyst (OOC is a relatively uncommon developmental cyst comprising about 10% of the cases that had been previously implied as odontogenic keratocysts. More than half of the cases of OOC are associated with impacted tooth; but not a single case of OOC associated with supernumerary teeth is reported. Hence, the purpose of this article is to report the first case of multiple supernumerary mandibular premolars associated with OOC in a 35-year-old male and to review the literature associated with multiple bilateral supernumerary mandibular premolars.

  2. Double dens invaginatus in an impacted molariform supernumerary tooth: An unique case

    Directory of Open Access Journals (Sweden)

    Anegundi R

    2008-05-01

    Full Text Available Dens invaginatus is a relatively rare developmental anomaly affecting usually the permanent maxillary lateral incisor. Various factors have been put forward regarding its pathogenesis. Involvement of crown/root has been reported as the coronal and radicular variety of dens invaginatus. One of the rarest variant is the Double dens invaginatus and only a few cases have been reported in the literature.This article focuses on a case of double dens invaginatus in an impacted maxillary anterior supernumerary tooth, the associated complications and its management

  3. Small supernumerary marker chromosomes (sSMC) in humans; are there B chromosomes hidden among them

    OpenAIRE

    Ogilvie Caroline; Kosyakova Nadezda; Mrasek Kristin; Liehr Thomas; Vermeesch Joris; Trifonov Vladimir; Rubtsov Nikolai

    2008-01-01

    Abstract Background Small supernumerary marker chromosomes (sSMC) and B-chromosomes represent a heterogeneous collection of chromosomes added to the typical karyotype, and which are both small in size. They may consist of heterochromatic and/or euchromatic material. Also a predominance of maternal transmission was reported for both groups. Even though sSMC and B-chromosomes show some similarity it is still an open question if B-chromosomes are present among the heterogeneous group of sSMC. Ac...

  4. A comparison between various radiological techniques in the localization and analysis of impacted and supernumerary teeth

    Directory of Open Access Journals (Sweden)

    Christoph M Ziegler

    2013-01-01

    Full Text Available Background and Objectives: An increasing number of different types of commercial cone-beam computed tomography (CBCT devices are available for three-dimensional (3D imaging in the field of dental and maxillofacial radiology. When removing impacted or supernumerary teeth, surgical teams often operate adjacent significant anatomical structures such as nerves, vessels, adjacent teeth roots, and paranasal sinuses. It is therefore important to choose the appropriate surgical approach to avoid iatrogenic damage to the essential anatomical neighbouring structures. CBCT, also called digital volume tomography (DVT, can visualize impacted and supernumerary teeth in all standard planes, as well as multisectional 3D views. These devices have shown to be highly beneficial in the assessment of small bony lesions and maxillofacial injuries. However, it is still necessary to determine the effectiveness of such devices in the assessment of impacted and supernumerary teeth, in comparison to the conventional radiological methods of intraoral X-rays and panoramic X-rays. Materials and Methods: During a period of 2 years, a total of 61 patients of whom majority had impacted teeth or supernumerary elements in the frontal maxillary region were studied with CBCT and treated at the St. Olavs University Hospital. Patients were referred to our Department of Oral and Maxillofacial Surgery with both conventional and digital intraoral X-rays and/or panoramic X-rays. None had any acute infections or odontogenic abscesses, and most presented with asymptomatic impacted tooth. A comparison between the preoperative conventional and the CBCT images, the resulting diagnoses, and the intraoperative findings as "gold standard" were made and recorded in a compiled scoring sheet. The objects of interest were researched with the magnification method. Each patient was identified only with a patient number. Results: In contrast to the conventional X-rays, the pre-surgical evaluation with

  5. Newborn with Supernumerary Marker Chromosome Derived from Chromosomes 11 And 22- A Case Report.

    Science.gov (United States)

    Vahidi Mehrjardi, Mohammad Yahya; Dehghan Tezerjani, Masoud; Nori-Shadkam, Mahmoud; Kalantar, Seyed Mehdi; Dehghani, Mohammadreza

    2016-03-01

    The interpretation of supernumerary chromosome is important for genetic counseling and prognosis. Here, we used SNP array and conventional karyotyping method to identify a denovo marker chromosome originated from chromosome 22 and 11 in a newborn transferred to the Neonatal Intensive Care Unit of Shahid Sadoughi Hospital in 2015. Clinical abnormalities identified in the newborn were dysmorphic face, intrauterine growth retardation, atrial septal defect (ASD), the hypoplasia of corpus callosum and septum pellucidum. These clinical abnormalities can be related to this marker, and it may help genetic counselor for predicting abnormality risk in susceptible individuals as well as prenatal diagnosis.

  6. Dioctophyme renale Goeze, 1782 in a cat with a supernumerary kidney

    Directory of Open Access Journals (Sweden)

    Daniela Pedrassani

    Full Text Available This study reports a case of parasitism by Dioctophyme renale in a supernumerary kidney and abdominal cavity of a female cat in Brazil. The three-year-old cat of indeterminate breed presented abdominal distension and was taken to the University of Contestado Veterinary Hospital in Canoinhas, state of Santa Catarina, since the owner suspected pregnancy. An ultrasound scan did not confirm pregnancy but revealed parasitism in the kidney. This case is worth reporting because domestic cats are rarely hosts of this nematode species.

  7. Dioctophyme renale Goeze, 1782 in a cat with a supernumerary kidney.

    Science.gov (United States)

    Pedrassani, Daniela; Wendt, Hamilton; Rennau, Erley Alexandre; Pereira, Samuel Tibes; Wendt, Simone Balão Taques

    2014-03-01

    This study reports a case of parasitism by Dioctophyme renale in a supernumerary kidney and abdominal cavity of a female cat in Brazil. The three-year-old cat of indeterminate breed presented abdominal distension and was taken to the University of Contestado Veterinary Hospital in Canoinhas, state of Santa Catarina, since the owner suspected pregnancy. An ultrasound scan did not confirm pregnancy but revealed parasitism in the kidney. This case is worth reporting because domestic cats are rarely hosts of this nematode species.

  8. Mandibular midline supernumerary tooth associated with agenesis of permanent central incisors: a diagnostic conundrum.

    Science.gov (United States)

    Marya, Charu Mohan; Sharma, Gaurav; Parashar, Vijay P; Dahiya, Vandana; Gupta, Anil

    2012-01-01

    Concomitant hypo-hyperdontia is a rare mixed numeric anomalous condition. The presence of this condition in the same area of dental arch and specifically in the mandibular anterior region is reported very infrequently. This case report presents a case of 20 years old male with congenitally missing permanent mandibular central incisors in conjunction with a mandibular midline supernumerary tooth. Only 3 cases have been documented in English literature till date. The article focuses on the review of mandibular mesiodens and the clarity regarding the usage of the terminology "mesiodens".

  9. Pindborg tumor arising in association with an impacted supernumerary tooth in the anterior maxilla.

    Science.gov (United States)

    Waingade, Manjushri; Gawande, Pushkar; Aditya, Amita; Medikeri, Raghavendra S

    2014-06-01

    Pindborg tumor/Calcifying Epithelial Odontogenic Tumor (CEOT) is a benign epithelial odontogenic tumor which shows locally aggressive behavior and accounts for less than 1% of all odontogenic tumors. The most frequent location is the mandibular premolar and molar area; less frequently the lesion is found in the maxilla. Since histopathology remains the main method for definitive diagnosis, this lesion presents an enigma to a clinician when lesions occur in atypical locations. The authors report a case of CEOT in the maxillary anterior region associated with an impacted supernumerary tooth (mesiodens).

  10. Prevalence and characterıstıcs of supernumerary teeth in a child population from Central Anatolıa - Turkey.

    Science.gov (United States)

    Arikan, Volkan; Ozgul, Betul Memis; Firdevs, Tulga O Z

    2013-12-01

    This article aimed to characterize the incidence of supernumerary teeth in Turkish children according to sex, location, number and morphology and to explore possible correlations between these variables. The study population comprised 7,551 non-syndromic patients aged 3-16 years who applied for routine check-ups at the Ankara University Department of Pediatric Dentistry between January 2009 and January 2010. The population included children in deciduous, mixed and permanent dentition. Both clinical and radiographic examinations were conducted. Demographic variables (age, sex) as well as number, location (maxilla or mandible), position, type and morphology of supernumeraries were recorded for all patients with supernumerary teeth. Supernumerary teeth with odontomes were also noted. Of the 7,551 patients examined, supernumerary teeth were detected in 74 patients (0.98%). Of these, 48 were male and 26 were female (male-to-female ratio: 1.84:1). A total of 84 supernumerary teeth were detected, 80 (95.2%) of which were permanent teeth and 4 (4.8%) of which were deciduous teeth (n=4). Most supernumerary teeth (n=59, 70.2%) were located in the maxillary arch. The most common supernumerary teeth were mesiodens (36.9%), followed by supernumerary teeth located in the maxillary incisor region (33.3%), the mandibular premolar region (17.9%), the mandibular molar region (5.9%), the mandibular incisor region (4.8%) and the mandibular canine region (1.2%). The prevalence of supernumerary teeth was found to be 0.98% and mesiodens was the most frequent type.

  11. 多发性多生牙1例%A case report of multiple supernumerary teeth

    Institute of Scientific and Technical Information of China (English)

    姜华

    2013-01-01

      多生牙的发生率占正常人群的1%~3%。多生牙常见于恒牙列,数目一般多见于1~3颗,5颗以上非常罕见。%Incidence of supernumerary teeth in total normal population is 1%-3%. Supernumerary teeth are com-mon in the permanent dentition, and 1-3 teeth are common, but more than 5 teeth are rare.

  12. Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning

    Directory of Open Access Journals (Sweden)

    Kanako Kumamoto

    2017-07-01

    Full Text Available The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG neurons. In contrast, exogenous LIS1 expression or endogenous LIS1 augmentation by calpain inhibition restored axonal extension capacity in mature DRG neurons and facilitated regeneration of the damaged sciatic nerve. The insulator protein CTCF suppressed LIS1 expression in mature DRG neurons, and this reduction resulted in excessive accumulation of phosphoactivated GSK-3β at the axon tip, causing failure of the axonal extension. Conversely, sustained LIS1 expression inhibited developmental axon pruning in the mammillary body. Thus, LIS1 regulation may coordinate the balance between axonal growth and pruning during maturation of neuronal circuits.

  13. Laser-based single-axon transection for high-content axon injury and regeneration studies.

    Directory of Open Access Journals (Sweden)

    Darío Kunik

    Full Text Available The investigation of the regenerative response of the neurons to axonal injury is essential to the development of new axoprotective therapies. Here we study the retinal neuronal RGC-5 cell line after laser transection, demonstrating that the ability of these cells to initiate a regenerative response correlates with axon length and cell motility after injury. We show that low energy picosecond laser pulses can achieve transection of unlabeled single axons in vitro and precisely induce damage with micron precision. We established the conditions to achieve axon transection, and characterized RGC-5 axon regeneration and cell body response using time-lapse microscopy. We developed an algorithm to analyze cell trajectories and established correlations between cell motility after injury, axon length, and the initiation of the regeneration response. The characterization of the motile response of axotomized RGC-5 cells showed that cells that were capable of repair or regrowth of damaged axons migrated more slowly than cells that could not. Moreover, we established that RGC-5 cells with long axons could not recover their injured axons, and such cells were much more motile. The platform we describe allows highly controlled axonal damage with subcellular resolution and the performance of high-content screening in cell cultures.

  14. Axon Death Pathways Converge on Axundead to Promote Functional and Structural Axon Disassembly.

    Science.gov (United States)

    Neukomm, Lukas J; Burdett, Thomas C; Seeds, Andrew M; Hampel, Stefanie; Coutinho-Budd, Jaeda C; Farley, Jonathan E; Wong, Jack; Karadeniz, Yonca B; Osterloh, Jeannette M; Sheehan, Amy E; Freeman, Marc R

    2017-07-05

    Axon degeneration is a hallmark of neurodegenerative disease and neural injury. Axotomy activates an intrinsic pro-degenerative axon death signaling cascade involving loss of the NAD(+) biosynthetic enzyme Nmnat/Nmnat2 in axons, activation of dSarm/Sarm1, and subsequent Sarm-dependent depletion of NAD(+). Here we identify Axundead (Axed) as a mediator of axon death. axed mutants suppress axon death in several types of axons for the lifespan of the fly and block the pro-degenerative effects of activated dSarm in vivo. Neurodegeneration induced by loss of the sole fly Nmnat ortholog is also fully blocked by axed, but not dsarm, mutants. Thus, pro-degenerative pathways activated by dSarm signaling or Nmnat elimination ultimately converge on Axed. Remarkably, severed axons morphologically preserved by axon death pathway mutations remain integrated in circuits and able to elicit complex behaviors after stimulation, indicating that blockade of axon death signaling results in long-term functional preservation of axons. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Paternal isodisomy of chromosome 6 in association with a maternal supernumerary marker chromosome (6)

    Energy Technology Data Exchange (ETDEWEB)

    James, R.S.; Crolla, J.A.; Sitch, F.L. [Salisbury District Hospital, Wiltshire (United Kingdom)] [and others

    1994-09-01

    Uniparental disomy may arise by a number of different mechanisms of aneuploidy correction. A population that has been identified as being at increased risk of aneuploidy are those individuals bearing supernumerary marker chromosomes (SMCs). There have been a number of cases reported of trisomy 21 in association with bi-satellited marker chromosomes have described two individuals with small inv dup (15) markers. One had paternal isodisomy of chromosome 15 and Angelman syndrome. The other had maternal heterodisomy (15) and Prader-Willi syndrome. At the Wessex Regional Genetics Laboratory we have conducted a search for uniparental disomy of the normal homologues of the chromosomes from which SMCs originated. Our study population consists of 39 probands with SMCs originating from a number of different autosomes, including 17 with SMCs of chromosome 15 origin. Using PCR amplification of microsatellite repeat sequences located distal to the regions included in the SMCs we have determined the parental origin of the two normal homologues in each case. We have identified paternal isodisomy of chromosome 6 in a female child with a supernumerary marker ring chromosome 6 in approximately 70% of peripheral blood lymphocytes. The marker was found to be of maternal origin. This is the second case of paternal isodisomy of chromosome 6 to be reported, and the first in association with a SMC resulting in a partial trisomy for a portion of the short arm of chromosome 6. In spite of this, the patient appears to be functioning appropriately for her age.

  16. Supernumerary Formation of Olfactory Glomeruli Induced by Chronic Odorant Exposure: A Constructivist Expression of Neural Plasticity

    Science.gov (United States)

    Valle-Leija, Pablo; Blanco-Hernández, Eduardo; Drucker-Colín, Rene; Gutiérrez-Ospina, Gabriel; Vidaltamayo, Roman

    2012-01-01

    It is accepted that sensory experience instructs the remodelling of neuronal circuits during postnatal development, after their specification has occurred. The story is less clear with regard to the role of experience during the initial formation of neuronal circuits, whether prenatal or postnatal, since this process is now supposed to be primarily influenced by genetic determinants and spontaneous neuronal firing. Here we evaluated this last issue by examining the effect that postnatal chronic exposure to cognate odorants has on the formation of I7 and M72 glomeruli, iterated olfactory circuits that are formed before and after birth, respectively. We took advantage of double knock-in mice whose I7 and M72 primary afferents express green fluorescent protein and β-galactosidase, correspondingly. Our results revealed that postnatal odorant chronic exposure led to the formation of permanent supernumerary I7 and M72 glomeruli in a dose and time dependent manner. Glomeruli in exposed mice were formed within the same regions of olfactory bulb and occupy small space volumes compared to the corresponding single circuits in non-exposed mice. We suggest that local reorganization of the primary afferents could participate in the process of formation of supernumerary glomeruli. Overall, our results support that sensory experience indeed instructs the permanent formation of specific glomeruli in the mouse olfactory bulb by means of constructivist processes. PMID:22511987

  17. Non-syndromic multiple impacted supernumerary teeth with peripheral giant cell granuloma

    Directory of Open Access Journals (Sweden)

    Pankaj Bansal

    2011-01-01

    Full Text Available Peripheral giant cell granuloma (PGCG is a relatively frequent benign reactive lesion of the gingiva, originating from the periosteum or periodontal membrane following local irritation or chronic trauma. PGCG manifests as a red-purple nodule located in the region of the gingiva or edentulous alveolar margins. The lesion can develop at any age, although it is more common between the second and third decades of life, and shows a slight female predilection. PGCG is a soft tissue lesion that very rarely affects the underlying bone, although the latter may suffer superficial erosion. A supernumerary tooth is one that is additional to the normal series and can be found in almost any region of the dental arch. These teeth may be single, multiple, erupted or unerupted and may or may not be associated with syndrome. Usually, they cause one or the other problem in eruption or alignment of teeth, but may also present without disturbing the normal occlusion or eruption pattern. Management of these teeth depends on the symptoms. Presented here is a case of PGCG in relation to the lower left permanent first molar with three supernumerary teeth in the mandibular arch but no associated syndrome.

  18. Analyses of 1100 supernumerary teeth in a nonsyndromic Turkish population: A retrospective multicenter study.

    Science.gov (United States)

    Bereket, C; Çakır-Özkan, N; Şener, İ; Bulut, E; Baştan, A İ

    2015-01-01

    The aim of this study was to analyze the clinical and radiological features of supernumerary teeth (ST), record the related complications, and discuss different forms of treatment. A total of 111,293 patients were examined over a 3-year period. The patients' ages and genders, in addition to the number, morphology, location, position, shape, developmental stage, and eruption status of ST and associated complications, were recorded. Among the 111,293 patients, there were 851 (0.76%) patients with 1100 ST. Of these patients, 478 (56.2%) were males, and 373 (43.8%) were females, with a mean age of 22.71. Most of the 1100 ST were located in the maxilla, 437 (39.72%) were a conical shape, with 82.81% of these including a fully developed tooth. A mesiodens was the most common type of supernumerary tooth (n=284, 33.37%), followed by distomolars (n=204, 23.97%) and parapremolars (n=146, 17.16%). Among the 1100 ST, 422 (38.36%) were associated with complications. No previous studies in the literature have examined in detail so many cases with ST. The demographic profile of the patients with ST presented herein provides useful additional epidemiological information.

  19. A rare case of impacted supernumerary premolar causing resorption of mandibular first molar

    Directory of Open Access Journals (Sweden)

    R V Murali

    2015-01-01

    Full Text Available The management of patients with pain in today′s general practice has become a major concern and sometimes this pain is related to some rare causes. A male patient aged 26 years reported with pain in the lower left molar region (36 and then an intra-oral periapical radiograph (IOPA, and orthopantomograph was taken. IOPA revealed the presence of supernumerary premolar causing pressure and root resorption of 36. Also, there was missing 21 and proximal decay in 11. Eleven was treated endodontically, and then bridge was done in relation to 11, 21 and 22. Lower anterior crowding was also present. The treatment plan was to extract 36 followed by orthodontic extrusion of the supernumerary premolar and also the correction of lower anterior crowding. Hidden approach (lingual orthodontics was used as the patient was insisting upon the braces not being seen outside during the course of the treatment. Later all ceramic bridge was done in relation to 11, 21 and 22. Orthodontic tooth extrusion techniques offer excellent treatment options for Partially Impacted tooth. It is a well-documented clinical method for extruding sound tooth material from within the alveolar socket by light forces. The use of lingual technique for forced eruption enhance acceptance of orthodontic treatment by adults. The treatment of a young adult patient illustrates the importance of treatment planning from one discipline to another, communication among team members and the benefits of working together in an interdisciplinary approach

  20. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    Science.gov (United States)

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  1. Clinical Report of 1 Cases of Monozygotic Twins Supernumerary Teeth%单卵双胞胎兄弟额外牙1例

    Institute of Scientific and Technical Information of China (English)

    杨春敏

    2014-01-01

    额外牙是指牙数目异常,其发生可能来自形成过多的牙蕾,也可能是牙胚分裂而成。临床上最多见的是上前牙区单颗多生牙。单卵双胞胎同患多生牙未见报道,同时含有2颗或多颗多生牙者更少见。近日笔者遇到一对双胞胎兄弟,因上前牙区多生牙影响美观前来就诊,由此正确的诊断及时拔除额外牙具有临床意义。%Supernumerary tooth is tooth abnormalities, which may be derived from the formation of excessive tooth bud, may also be split into tooth germ. Clinical go up to see at most is the anterior teeth area single supernumerary teeth. Monozygotic twins with supernumerary teeth is not reported, while containing two or more supernumerary teeth are more rare. I recently met a pair of twin brothers, because to supernumerary teeth appearance came to visit, report as fol ows now.Because the forward supernumerary teeth af ect the appearance to come round to see a doctor, the clinical significance of the correct diagnosis and timely removal of supernumerary teeth. Report as fol ows now.

  2. Molecular cytogenetic characterization of a small, familial supernumerary ring chromosome 7 associated with mental retardation and an abnormal phenotype

    NARCIS (Netherlands)

    Tan-Sindhunata, G; Castedo, S; Leegte, B; Mulder, [No Value; van der Veen, AYV; van der Hout, AHV; van Essen, AJ

    2000-01-01

    A family is described in which a mother and two of her children were mosaic for a small supernumerary ring chromosome. As the origin of the ring chromosome could not be determined by routine cytogenetic studies, fluorescent in situ hybridization was performed, which indicated that the ring chromosom

  3. Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies

    NARCIS (Netherlands)

    L.T. van der Veken (Lars); M.M.J. Dieleman (Marianne); H. Douben (Hannie); J.C. van de Brug (Judith); R. van de Graaf (Raoul); A.J.M. Hoogeboom; P.J. Poddighe (Pino); J.E.M.M. de Klein (Annelies)

    2010-01-01

    textabstractBackground. Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities mi

  4. Phenotypic Spectrum of 20 Novel Patients With Molecularly Defined Supernumerary Marker Chromosomes 15 and a Review of the Literature

    NARCIS (Netherlands)

    Kleefstra, Tjitske; de Leeuw, Nicole; Wolf, Roy; Nillesen, Willy M.; Schobers, Gaby; Mieloo, Hanneke; Willemsen, Marjolein; Perrotta, Concetta Simona; Poddighe, Pino J.; Feenstra, Ilse; Draaisma, Jos; van Ravenswaaij-Arts, Conny M. A.

    Supernumerary marker chromosomes (SMC) originating from chromosome 15 are the most common SMCs. They encompass clinically irrelevant SMC(15)s containing only heterochromatin and 15p material, and clinically relevant SMC(15)s that consist of both eu- and heterochromatic 15q material. On the basis of

  5. Phenotypic Spectrum of 20 Novel Patients With Molecularly Defined Supernumerary Marker Chromosomes 15 and a Review of the Literature

    NARCIS (Netherlands)

    Kleefstra, Tjitske; de Leeuw, Nicole; Wolf, Roy; Nillesen, Willy M.; Schobers, Gaby; Mieloo, Hanneke; Willemsen, Marjolein; Perrotta, Concetta Simona; Poddighe, Pino J.; Feenstra, Ilse; Draaisma, Jos; van Ravenswaaij-Arts, Conny M. A.

    2010-01-01

    Supernumerary marker chromosomes (SMC) originating from chromosome 15 are the most common SMCs. They encompass clinically irrelevant SMC(15)s containing only heterochromatin and 15p material, and clinically relevant SMC(15)s that consist of both eu- and heterochromatic 15q material. On the basis of

  6. Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering

    Science.gov (United States)

    Šmít, Daniel; Fouquet, Coralie; Pincet, Frédéric; Zapotocky, Martin; Trembleau, Alain

    2017-01-01

    While axon fasciculation plays a key role in the development of neural networks, very little is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behavior that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and mechanical tension in the axons, and provide the first quantification of the force of axon-axon adhesion. Furthermore, we introduce a biophysical model of the zippering dynamics, and we quantitatively relate the individual zipper properties to global characteristics of the developing axon network. Our study uncovers a new role of mechanical tension in neural development: the regulation of axon fasciculation. DOI: http://dx.doi.org/10.7554/eLife.19907.001 PMID:28422009

  7. Genetic dissection of myelinated axons in zebrafish

    OpenAIRE

    2009-01-01

    In the vertebrate nervous system, the myelin sheath allows for rapid and efficient conduction of action potentials along axons. Despite the essential function of myelin, many questions remain unanswered about the mechanisms that govern the development of myelinated axons. The fundamental properties of myelin are widely shared among vertebrates, and the zebrafish has emerged as a powerful system to study myelination in vivo. This review will highlight recent advances from genetic screens in ze...

  8. Human Genetic Disorders of Axon Guidance

    OpenAIRE

    Engle, Elizabeth C

    2010-01-01

    This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Gene...

  9. Crossing axons in the third nerve nucleus.

    Science.gov (United States)

    Bienfang, D C

    1975-12-01

    The research presented in this paper studied the pathway taken by the crossed fibers of the third nerve nucleus in an animal whose nucleus has been well mapped and found to correlate well with higher mammals and man. Autoradiography using tritiated amino acid labeled the cell bodies an axons of the left side of the oculomotor nucleus of the cat. Axons so labeled could be seen emerging from the ventral portion of the left nucleus through the median longitudinal fasciculus (mlf) to join the left oculomotor nerve. Labeled axons were also seen to emerge from the medial border of the caudal left nucleus, cross the midline, and pass through the right nucleus and the right mlf to join the right oculomotor nerve. These latter axons must be the crossed axons of the superior rectus and levator palpebrae subnuclei. Since the path of these crossed axons is through the caudal portion of the nucleus of the opposite side, the destruction of one lateral half of the oculomotor nucleus would result in a bilateral palsy of the crossed subnuclei. Bilateral palsy of the superior rectus and bilateral assymetrical palsy of the levator palpebrae muscles would result.

  10. Delayed feedback model of axonal length sensing.

    Science.gov (United States)

    Karamched, Bhargav R; Bressloff, Paul C

    2015-05-05

    A fundamental question in cell biology is how the sizes of cells and organelles are regulated at various stages of development. Size homeostasis is particularly challenging for neurons, whose axons can extend from hundreds of microns to meters (in humans). Recently, a molecular-motor-based mechanism for axonal length sensing has been proposed, in which axonal length is encoded by the frequency of an oscillating retrograde signal. In this article, we develop a mathematical model of this length-sensing mechanism in which advection-diffusion equations for bidirectional motor transport are coupled to a chemical signaling network. We show that chemical oscillations emerge due to delayed negative feedback via a Hopf bifurcation, resulting in a frequency that is a monotonically decreasing function of axonal length. Knockdown of either kinesin or dynein causes an increase in the oscillation frequency, suggesting that the length-sensing mechanism would produce longer axons, which is consistent with experimental findings. One major prediction of the model is that fluctuations in the transport of molecular motors lead to a reduction in the reliability of the frequency-encoding mechanism for long axons. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. SARM1 activation triggers axon degeneration locally via NAD+ destruction

    OpenAIRE

    Gerdts, Josiah; Brace, E. J.; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2015-01-01

    Axon degeneration is an intrinsic self-destruction program that underlies axon loss during injury and disease. Sterile alpha and TIR motif containing 1 (SARM1) protein is an essential mediator of axon degeneration. We report that SARM1 initiates a local destruction program involving rapid breakdown of NAD+ after injury. We used an engineered protease-sensitized SARM1 to demonstrate that SARM1 activity is required after axon injury to induce axon degeneration. Dimerization of the Toll-Interleu...

  12. Fibroadenoma in Axillary Supernumerary Breast in a 17-Year-Old Girl: Case Report.

    Science.gov (United States)

    Surd, Adrian; Mironescu, Aurel; Gocan, Horatiu

    2016-10-01

    Supernumerary breast or polymastia is a well documented anomaly of the breast, and commonly presents along the embryonic milk line extending between the axilla and groin. However, cases of polymastia have been recorded in the face, vulva, and perineum. The clinical significance of these anomalies include their susceptibility to inflammatory and malignant changes, and their association with other congenital anomalies of the urinary and cardiovascular systems. In this article we report a case of fibroadenoma that developed in the supernumerary breast of the right axilla in a 17-year-old girl. It is uncommon to find such palpable masses in young patients. Clinical and sonographic examination of both breasts revealed no abnormalities and no lymph nodes were detected in the axillae or the neck. No associated urologic or cardiovascular abnormalities were found, and the histopathological examination of the excisional biopsy samples showed a well-defined, capsulated intracanalicular type of fibroadenoma similar to that of eutopic mammary tissue. In this report, we describe a rare case of fibroadenoma in an accessory breast in a young woman. There are a fewer than 40 reports in the world about this subject, of which differential diagnoses include: cancer in axillary supernumerary breast, hidradenitis, axillary lymphadenomegaly, lipomas, anexial cutaneous neoplasia, cysts, and phylloides tumor. The combination of clinical examination, ultrasound, and cytology leads to adequate treatment, especially surgical. The diagnosis could be confused because of findings from cytology. In this case, because of the clinical and sonographic findings and multiple differential diagnosis, only the histopathological study was used to confirm the diagnosis. Despite its high sensitivity, cytology has low specificity and could create false positive results. However, atypical lesions can be seen in fibroadenomas, especially in younger patients, pregnant patients, and in patients who use hormonal

  13. Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus

    Directory of Open Access Journals (Sweden)

    Carla M Lopez

    2012-11-01

    Full Text Available In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus subfield (DG exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs and immature recently born GCs that are generated throughout adult life (young GCs, providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3-6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the

  14. Supernumerary rainbows

    Science.gov (United States)

    Sawicki, Mikolaj; Sawicki, Pawel

    2000-01-01

    Late in the afternoon of July 19, 1999, we were able to photograph some very unusual rainbows in the sky over Boulder, Colorado. The picture here shows a primary rainbow, a fainter secondary bow above it, and several pastel-shaded rainbows inside the primary one. While we think we counted as many as four concurrent rainbows in that afternoon, only three of them show up in developed prints.

  15. Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase.

    Science.gov (United States)

    Chen, Lizhen; Chuang, Marian; Koorman, Thijs; Boxem, Mike; Jin, Yishi; Chisholm, Andrew D

    2015-09-04

    Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In Caenorhabditis elegans the signaling protein Exchange Factor for ARF-6 (EFA-6) is a potent intrinsic inhibitor of axon regrowth. Here we show that axon injury triggers rapid EFA-6-dependent inhibition of axonal microtubule (MT) dynamics, concomitant with relocalization of EFA-6. EFA-6 relocalization and axon regrowth inhibition require a conserved 18-aa motif in its otherwise intrinsically disordered N-terminal domain. The EFA-6 N-terminus binds the MT-associated proteins TAC-1/Transforming-Acidic-Coiled-Coil, and ZYG-8/Doublecortin-Like-Kinase, both of which are required for regenerative growth cone formation, and which act downstream of EFA-6. After injury TAC-1 and EFA-6 transiently relocalize to sites marked by the MT minus end binding protein PTRN-1/Patronin. We propose that EFA-6 acts as a bifunctional injury-responsive regulator of axonal MT dynamics, acting at the cell cortex in the steady state and at MT minus ends after injury.

  16. Paradental cyst associated with supernumerary tooth fused with third molar: A rare case report

    Directory of Open Access Journals (Sweden)

    A Ravi Prakash

    2012-01-01

    Full Text Available Fusion is the union of two tooth buds that are normally separated. Fusion is more frequent in deciduous teeth, particularly in the anterior region. The etiology of fusion is not known. It has been suggested that the pressure of adjacent dental follicles produces their contact and fusion before calcification. There is no difference between men and women in incidence. The term paradental cyst means that such type of cysts that are close proximity with the root of a tooth. A history of recurrent pericoronitis is reported usually and there is often the presence of a communication between the periodontal pocket and the cyst. We present a rare case report where in partially erupted mandibular third molar is fused horizontally with a supernumerary tooth with paradental cyst.

  17. Paradental cyst associated with supernumerary tooth fused with third molar: A rare case report

    Science.gov (United States)

    Prakash, A Ravi; Reddy, P Sreenivas; Rajanikanth, M

    2012-01-01

    Fusion is the union of two tooth buds that are normally separated. Fusion is more frequent in deciduous teeth, particularly in the anterior region. The etiology of fusion is not known. It has been suggested that the pressure of adjacent dental follicles produces their contact and fusion before calcification. There is no difference between men and women in incidence. The term paradental cyst means that such type of cysts that are close proximity with the root of a tooth. A history of recurrent pericoronitis is reported usually and there is often the presence of a communication between the periodontal pocket and the cyst. We present a rare case report where in partially erupted mandibular third molar is fused horizontally with a supernumerary tooth with paradental cyst. PMID:22434950

  18. Cleidocranial dysplasia presenting with retained deciduous teeth and impacted permanent and supernumerary teeth

    Directory of Open Access Journals (Sweden)

    Mahalakshmi Ikkanur Puttaranganaik

    2014-01-01

    Full Text Available Cleidocranial dysplasia is a disease that occurs secondary to a dominant autosomal inheritance. There is no predilection for any genre or ethnic group. As there is a delay in the eruption and/or absence of permanent teeth, the patients usually report to a dental surgeon for replacement of the missing teeth. This condition is characterized by several cranial malformations and underdevelopment, absence of clavicles, and multiple impacted supernumerary and permanent teeth. The diagnosis of the condition is usually based on the presence of the above-mentioned main features and on clinical and familial evidence. Here we report a rare case of cleidocranial dysplasia in a male patient, having most of the characteristic features of this syndrome.

  19. Caries, Periodontal Disease, Supernumerary Teeth and Other Dental Disorders in Swedish Wild Boar (Sus scrofa).

    Science.gov (United States)

    Malmsten, A; Dalin, A-M; Pettersson, A

    2015-07-01

    Between January and December 2013, the dental and periodontal health of 99 Swedish wild boars (Sus scrofa) was investigated. Sampling occurred in conjunction with routine hunting at six large estates in the southern and middle parts of Sweden. All six of the estates use supplemental feeding. The weight of the animals, their sex and their dates of death were noted. Age was estimated using tooth eruption and tooth replacement patterns. The oral cavity was inspected and abnormalities were recorded on a dental chart modified for wild boars. The findings included supernumerary teeth, absence of teeth, mild class II malocclusion, severe tooth wear, periodontitis, calculus, caries, tooth fractures and the presence of enamel defects. Swedish wild boars suffer from different dental lesions and the impact of supplemental feeding on dental and periodontal health is still to be investigated.

  20. Removal of Supernumerary Teeth Utilizing a Computer-Aided Design/Computer-Aided Manufacturing Surgical Guide.

    Science.gov (United States)

    Jo, Chanwoo; Bae, Doohwan; Choi, Byungho; Kim, Jihun

    2017-05-01

    Supernumerary teeth need to be removed because they can cause various complications. Caution is needed because their removal can cause damage to permanent teeth or tooth germs in the local vicinity. Surgical guides have recently been used in maxillofacial surgery. Because surgical guides are designed through preoperative analysis by computer-aided design software and fabricated using a 3-dimensional printer applying computer-aided manufacturing technology, they increase the accuracy and predictability of surgery. This report describes 2 cases of removal of a mesiodens-1 from a child and 1 from an adolescent-using a surgical guide; these would have been difficult to remove with conventional surgical methods. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Atypical supernumerary phantom limb and phantom limb pain in two patients with pontine hemorrhage.

    Science.gov (United States)

    Yoo, Seung Don; Kim, Dong Hwan; Jeong, Yong Seol; Chon, Jinmann; Bark, Jihea

    2011-06-01

    Phantom limbs are usually observed after amputation of extremities. In patients after a stroke, a similar but rarely occurring phenomenon consisting of the patient experiencing the presence of an additional limb has been described. This phenomenon, generally called supernumerary phantom limb (SPL), may be caused by lesions in the right or left cerebral hemisphere, but has been predominantly reported in patients who have had a right hemispheric stroke. We report two cases of atypical SPL and phantom limb pain (PLP) after pontine hemorrhage. The patients were treated conservatively and their symptoms lasted more than 1 month. This is the first report of SPLs after left pontine hemorrhage, and phantom perception and pain lasted longer than those in previously observed cases. Our results indicate that SPL may be more common than reported; therefore, thorough examinations are essential for the care of stroke patients.

  2. How Schwann Cells Sort Axons: New Concepts.

    Science.gov (United States)

    Feltri, M Laura; Poitelon, Yannick; Previtali, Stefano Carlo

    2016-06-01

    Peripheral nerves contain large myelinated and small unmyelinated (Remak) fibers that perform different functions. The choice to myelinate or not is dictated to Schwann cells by the axon itself, based on the amount of neuregulin I-type III exposed on its membrane. Peripheral axons are more important in determining the final myelination fate than central axons, and the implications for this difference in Schwann cells and oligodendrocytes are discussed. Interestingly, this choice is reversible during pathology, accounting for the remarkable plasticity of Schwann cells, and contributing to the regenerative potential of the peripheral nervous system. Radial sorting is the process by which Schwann cells choose larger axons to myelinate during development. This crucial morphogenetic step is a prerequisite for myelination and for differentiation of Remak fibers, and is arrested in human diseases due to mutations in genes coding for extracellular matrix and linkage molecules. In this review we will summarize progresses made in the last years by a flurry of reverse genetic experiments in mice and fish. This work revealed novel molecules that control radial sorting, and contributed unexpected ideas to our understanding of the cellular and molecular mechanisms that control radial sorting of axons.

  3. Epigenetic regulation of axon and dendrite growth

    Directory of Open Access Journals (Sweden)

    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  4. Protein phosphorylation: Localization in regenerating optic axons

    Energy Technology Data Exchange (ETDEWEB)

    Larrivee, D. (Cornell Univ. Medical College, New York, NY (USA))

    1990-09-01

    A number of axonal proteins display changes in phosphorylation during goldfish optic nerve regeneration. (1) To determine whether the phosphorylation of these proteins was closely linked to their synthesis in the retinal ganglion cell body, cycloheximide was injected intraocularly into goldfish whose optic nerves had been regenerating for 3 weeks. Cycloheximide reduced the incorporation of (3H)proline and 32P orthophosphate into total nerve protein by 84% and 46%, respectively. Of the 20 individual proteins examined, 17 contained less than 15% of the (3H)proline label measured in corresponding controls, whereas 18 proteins contained 50% or more of the 32P label, suggesting that phosphorylation was largely independent of synthesis. (2) To determine whether the proteins were phosphorylated in the ganglion cell axons, axonal transport of proteins was blocked by intraocular injection of vincristine. Vincristine reduced (3H)proline labeling of total protein by 88% and 32P labeling by 49%. Among the individual proteins (3H)proline labeling was reduced by 90% or more in 18 cases but 32P labeling was reduced only by 50% or less. (3) When 32P was injected into the cranial cavity near the ends of the optic axons, all of the phosphoproteins were labeled more intensely in the optic tract than in the optic nerve. These results suggest that most of the major phosphoproteins that undergo changes in phosphorylation in the course of regeneration are phosphorylated in the optic axons.

  5. Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ

    Science.gov (United States)

    Zarei, Kasra; Scheetz, Todd E.; Christopher, Mark; Miller, Kathy; Hedberg-Buenz, Adam; Tandon, Anamika; Anderson, Michael G.; Fingert, John H.; Abràmoff, Michael David

    2016-05-01

    We have developed a publicly available tool, AxonJ, which quantifies the axons in optic nerve sections of rodents stained with paraphenylenediamine (PPD). In this study, we compare AxonJ’s performance to human experts on 100x and 40x images of optic nerve sections obtained from multiple strains of mice, including mice with defects relevant to glaucoma. AxonJ produced reliable axon counts with high sensitivity of 0.959 and high precision of 0.907, high repeatability of 0.95 when compared to a gold-standard of manual assessments and high correlation of 0.882 to the glaucoma damage staging of a previously published dataset. AxonJ allows analyses that are quantitative, consistent, fully-automated, parameter-free, and rapid on whole optic nerve sections at 40x. As a freely available ImageJ plugin that requires no highly specialized equipment to utilize, AxonJ represents a powerful new community resource augmenting studies of the optic nerve using mice.

  6. Diverse modes of axon elaboration in the developing neocortex.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available The development of axonal arbors is a critical step in the establishment of precise neural circuits, but relatively little is known about the mechanisms of axonal elaboration in the neocortex. We used in vivo two-photon time-lapse microscopy to image axons in the neocortex of green fluorescent protein-transgenic mice over the first 3 wk of postnatal development. This period spans the elaboration of thalamocortical (TC and Cajal-Retzius (CR axons and cortical synaptogenesis. Layer 1 collaterals of TC and CR axons were imaged repeatedly over time scales ranging from minutes up to days, and their growth and pruning were analyzed. The structure and dynamics of TC and CR axons differed profoundly. Branches of TC axons terminated in small, bulbous growth cones, while CR axon branch tips had large growth cones with numerous long filopodia. TC axons grew rapidly in straight paths, with frequent interstitial branch additions, while CR axons grew more slowly along tortuous paths. For both types of axon, new branches appeared at interstitial sites along the axon shaft and did not involve growth cone splitting. Pruning occurred via retraction of small axon branches (tens of microns, at both CR and TC axons or degeneration of large portions of the arbor (hundreds of microns, for TC axons only. The balance between growth and retraction favored overall growth, but only by a slight margin. Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons.

  7. Differences in excitability between median and superficial radial sensory axons.

    Science.gov (United States)

    Fujimaki, Yumi; Kanai, Kazuaki; Misawa, Sonoko; Shibuya, Kazumoto; Isose, Sagiri; Nasu, Saiko; Sekiguchi, Yukari; Ohmori, Shigeki; Noto, Yu-ichi; Kugio, Yumiko; Shimizu, Toshio; Matsubara, Shiro; Lin, Cindy S Y; Kuwabara, Satoshi

    2012-07-01

    The aim of this study was to investigate differences in excitability properties of human median and superficial radial sensory axons (e.g., axons innervating the glabrous and hairy skin in the hand). Previous studies have shown that excitability properties differ between motor and sensory axons, and even among sensory axons between median and sural sensory axons. In 21 healthy subjects, threshold tracking was used to examine excitability indices such as strength-duration time constant, threshold electrotonus, supernormality, and threshold change at the 0.2 ms inter-stimulus interval in latent addition. In addition, threshold changes induced by ischemia for 10 min were compared between median and superficial radial sensory axons. Compared with radial sensory axons, median axons showed shorter strength-duration time constant, greater threshold changes in threshold electrotonus (fanning-out), greater supernormality, and smaller threshold changes in latent addition. Threshold changes in both during and after ischemia were greater for median axons. These findings suggest that membrane potential in human median sensory axons is more negative than in superficial radial axons, possibly due to greater activity of electrogenic Na(+)/K(+) pump. These results may reflect adaptation to impulses load carried by median axons that would be far greater with a higher frequency. Biophysical properties are not identical in different human sensory axons, and therefore their responses to disease may differ. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons

    Science.gov (United States)

    Merianda, Tanuja T.; Jin, Ying

    2017-01-01

    Abstract The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons. PMID:28197547

  9. Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons.

    Science.gov (United States)

    Merianda, Tanuja T; Jin, Ying; Kalinski, Ashley L; Sahoo, Pabitra K; Fischer, Itzhak; Twiss, Jeffery L

    2017-01-01

    The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons.

  10. Molecular cytogenetic characterization of a small, familial supernumerary ring chromosome 7 associated with mental retardation and an abnormal phenotype.

    Science.gov (United States)

    Tan-Sindhunata, G; Castedo, S; Leegte, B; Mulder, I; vd Veen, A Y; vd Hout, A H; Wiersma, T J; van Essen, A J

    2000-05-15

    A family is described in which a mother and two of her children were mosaic for a small supernumerary ring chromosome. As the origin of the ring chromosome could not be determined by routine cytogenetic studies, fluorescent in situ hybridization was performed, which indicated that the ring chromosome was derived from the pericentromeric region of chromosome 7. Further characterization with a YAC-probe showed the involvement of the proximal q-arm of chromosome 7. Both sibs had speech difficulties and were mildly mentally retarded whereas the mother's intelligence was at the lower end of the normal range. They all had an unusual face, characterized by a flat profile, short forehead, downslant of the palpebral fissures, high and broad nasal bridge, simply formed ears, and prognathia. This is the second report of a small supernumerary ring chromosome derived from the pericentromeric region of chromosome 7, and the described clinical phenotype differs from that delineated in the previous report.

  11. Autotransplantation of a Supernumerary Tooth to Replace a Misaligned Incisor with Abnormal Dimensions and Morphology: 2-Year Follow-Up

    Directory of Open Access Journals (Sweden)

    R. Ebru Tirali

    2013-01-01

    Full Text Available Autotransplantation is a viable treatment option to restore esthetics and function impaired by abnormally shaped teeth when a suitable donors tooth is available. This paper describes the autotransplantation and 2-year follow-up of a supernumerary maxillary incisor as a replacement to a misaligned maxillary incisor with abnormal crown morphology and size. The supernumerary incisor was immediately autotransplanted into the extraction site of the large incisor and was stabilized with a bonded semirigid splint for 2 weeks. Fixed orthodontic therapy was initiated 3 months after autotransplantation. Ideal alignment of the incisors was accomplished after 6 months along with radiographic evidence of apical closure and osseous/periodontal regeneration. In autogenous tooth transplantation, a successful clinical outcome can be achieved if the cases are selected and treated properly.

  12. Sarjeev′s supernumerary tooth notation system: A universally compatible add-on to the Two-Digit system

    Directory of Open Access Journals (Sweden)

    Sarjeev Singh Yadav

    2013-01-01

    Full Text Available Aim: To give notation for quadrants, tooth position, and the type of supernumerary teeth for both permanent and deciduous dentition. Tooth numbering provides dentists with an essential shortcut in clinical record keeping. Materials and Methods: Three systems are favored worldwide: the Zsigmondy/Palmer system, the Universal system, and the Federation Dentaire Internationale (FDI Two-Digit system. Histories of all tooth-numbering methods were traced and the strengths and deficiencies of each system were reviewed. The FDI Two-Digit system is widely used throughout the world, except USA, and is the only method that makes the visual sense, cognitive sense, and computer sense. Conclusion: On review it was noticed that all tooth notation systems in vogue have a drawback as they do not provide any information or notations for supernumerary teeth such as paramolar, distomolar, mesiodens, and fused teeth.

  13. Sarjeev's supernumerary tooth notation system: a universally compatible add-on to the Two-Digit system.

    Science.gov (United States)

    Yadav, Sarjeev Singh; Sonkurla, Sapna

    2013-01-01

    To give notation for quadrants, tooth position, and the type of supernumerary teeth for both permanent and deciduous dentition. Tooth numbering provides dentists with an essential shortcut in clinical record keeping. Three systems are favored worldwide: the Zsigmondy/Palmer system, the Universal system, and the Federation Dentaire Internationale (FDI) Two-Digit system. Histories of all tooth-numbering methods were traced and the strengths and deficiencies of each system were reviewed. The FDI Two-Digit system is widely used throughout the world, except USA, and is the only method that makes the visual sense, cognitive sense, and computer sense. On review it was noticed that all tooth notation systems in vogue have a drawback as they do not provide any information or notations for supernumerary teeth such as paramolar, distomolar, mesiodens, and fused teeth.

  14. Management of fused supernumerary teeth in children using guided tissue regeneration: long-term follow up of 2 cases.

    Science.gov (United States)

    Olsen, Christopher B; Johnston, Timothy; Desai, Mala; Peake, Gregory G

    2002-01-01

    Surgical separation of supernumerary teeth fused to permanent incisor teethhas typically given rise to residual post surgical periodontal defects, induding loss of attachment and deep periodontal pocketing with persistent inflammation. Other complications include devitalisation of the retained tooth section, ankylosis, external and replacement resorption. A unique technique of using guided tissue regeneration has been successfully employed to promote periodontal healing, after 2 cases of surgical removal of a supernumerary tooth fused to a permanent maxillary lateral incisor tooth. In the first case, a 2-stage guided tissue regeneration technique was completed with a nonresorbable Gor-Tex membrane, and was followed up after 9 years. The second case was completed using a resorbable Vicryl membrane, in a single-stage guided tissue regenerative technique; and was followed up after 5 years.

  15. Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies

    Directory of Open Access Journals (Sweden)

    Hoogeboom A Jeannette M

    2010-07-01

    Full Text Available Abstract Background Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Results We report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BAC-probes located in the region indicated the presence of 6 signals on the r(18 chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy. Conclusions We report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11.

  16. Myelin-associated glycoprotein and its axonal receptors.

    Science.gov (United States)

    Schnaar, Ronald L; Lopez, Pablo H H

    2009-11-15

    Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons to halt elongation. Both the stabilizing and the axon outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors on the axon surface. Two MAG receptor families have been described, sialoglycans (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs). Controversies remain about which receptor(s) mediates which of MAG's biological effects. Here we review the findings and challenges in associating MAG's biological effects with specific receptors.

  17. The pathophysiology of axonal transport in alzheimer’s disease

    OpenAIRE

    Vicario Orri, Elena; Opazo, Carlos; Muñoz López, Francisco José, 1964-

    2015-01-01

    Neurons communicate in the nervous system by carrying out information along the length of their axons to finally transmit it at the synapse. Proper function of axons and axon terminals relies on the transport of proteins, organelles, vesicles, and other elements from the site of synthesis in the cell body. Conversely, neurotrophins secreted from axonal targets and other components at nerve terminals need to travel toward the cell body for clearance. Molecular motors, namely kinesins and dynei...

  18. Internodal function in normal and regenerated mammalian axons

    DEFF Research Database (Denmark)

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found...... that internodes play an active role in axonal function. RESULTS: By investigating internodal contribution to axonal excitability we have found evidence that axonal function may be permanently compromised in regenerated nerves. Furthermore, we illustrate that internodal function is also abnormal in regenerated...

  19. Modeling molecular mechanisms in the axon

    Science.gov (United States)

    de Rooij, R.; Miller, K. E.; Kuhl, E.

    2017-03-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

  20. A Microfluidics Approach to Investigate Axon Guidance

    Science.gov (United States)

    2007-03-26

    coat the substrate with PLL. The cells of one dissociated embryonic spinal cord was re-suspended in 3 µl of freshly-prepared Modified Frog Ringer’s...Surround repulsion of spinal sensory axons in higher vertebrate embryos . Neuron 18, 889-897 (1997). 8. Colamarino, S. & Tessier-Lavigne, M. The

  1. Mechanisms of axon degeneration: from development to disease.

    Science.gov (United States)

    Saxena, Smita; Caroni, Pico

    2007-10-01

    Axon degeneration is an active, tightly controlled and versatile process of axon segment self-destruction. Although not involving cell death, it resembles apoptosis in its logics. It involves three distinct steps: induction of competence in specific neurons, triggering of degeneration at defined axon segments of competent neurons, and rapid fragmentation and removal of the segments. The mechanisms that initiate degeneration are specific to individual settings, but the final pathway of pruning is shared; it involves microtubule disassembly, axon swellings, axon fragmentation, and removal of the remnants by locally recruited phagocytes. The tight regulatory properties of axon degeneration distinguish it from passive loss phenomena, and confer significance to processes that involve it. Axon degeneration has prominent roles in development, upon lesions and in disease. In development, it couples the progressive specification of neurons and circuits to the removal of defined axon branches. Competence might involve transcriptional switches, and local triggering can involve axon guidance molecules and synaptic activity patterns. Lesion-induced Wallerian degeneration is inhibited in the presence of Wld(S) fusion protein in neurons; it involves early local, and later, distal degeneration. It has recently become clear that like in other settings, axon degeneration in disease is a rapid and specific process, which should not be confused with a variety of disease-related pathologies. Elucidating the specific mechanisms that initiate axon degeneration should open up new avenues to investigate principles of circuit assembly and plasticity, to uncover mechanisms of disease progression, and to identify ways of protecting synapses and axons in disease.

  2. Morphometry of Axons in Optic Nerves of Siamese's Twins

    Institute of Scientific and Technical Information of China (English)

    Xinzu Gu; Zhenping Zhang; Qi Lin; Jiongji Liang; Wenyu Lu; Xiulan Ye; A A Sadun

    2002-01-01

    Purpose: To observe the development of optic nerve, we examined four optic nerves from Siameses Twins by absolute counts of axons.Methods: Mean axon diameter, mean axon density, totally axonal population and optic nerve area were noted for each optic nerve. The mean axon diameter and the mean axon density were compared between paraxial (inner sectors)and cortical (outer sectors)areas of the nerves.Results: More myelinated axons were seen in the inner sectors as compared to the outer sectors(average 11 axons/1 000 μm2 in inner sectors and 34 axons/l 000 μm2 in outer sectors( P=0. 036) . The myelinated fibers were also smaller(63 microns) in the outer sectors as compared to the inner sectors(72 microns) ( P = 0. 001 ). The average cross sectors area for the four 40 week stage optical nerves of Siamese Twins was 3.32 × 103 as compared to 1 million axons for 32-week-old normals.Conclusion: Our finding of fewer axonal number and small myelinated fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in the paraxial optic nerve than that in the peripheral sectors, suggesting anomalous development of optic nerve peripherally and delayed developnent centrally. Axonal density is higher in inner sectors than that in outer sectors, suggesting delayed development of the outer nerve sector.

  3. MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2

    Science.gov (United States)

    Walker, Lauren J; Summers, Daniel W; Sasaki, Yo; Brace, EJ; Milbrandt, Jeffrey; DiAntonio, Aaron

    2017-01-01

    Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD+ biosynthetic enzyme NMNAT2 that inhibits activation of the SARM1 pathway. Here we investigate the mechanism by which MAPK signaling facilitates axonal degeneration. We show that MAPK signaling promotes the turnover of the axonal survival factor NMNAT2 in cultured mammalian neurons as well as the Drosophila ortholog dNMNAT in motoneurons. The increased levels of NMNAT2 are required for the axonal protection caused by loss of MAPK signaling. Regulation of NMNAT2 by MAPK signaling does not require SARM1, and so cannot be downstream of SARM1. Hence, pro-degenerative MAPK signaling functions upstream of SARM1 by limiting the levels of the essential axonal survival factor NMNAT2 to promote injury-dependent SARM1 activation. These findings are consistent with a linear molecular pathway for the axonal degeneration program. DOI: http://dx.doi.org/10.7554/eLife.22540.001 PMID:28095293

  4. AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage

    Directory of Open Access Journals (Sweden)

    Yang Li

    2014-02-01

    Full Text Available Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an ‘axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders. © 2014 S. Karger AG, Basel

  5. Beyond the big five: the Dark Triad and the supernumerary personality inventory.

    Science.gov (United States)

    Veselka, Livia; Schermer, Julie Aitken; Vernon, Philip A

    2011-04-01

    The Dark Triad of personality, comprising Machiavellianism, narcissism, and psychopathy, was investigated in relation to the Supernumerary Personality Inventory (SPI) traits, because both sets of variables are predominantly distinct from the Big Five model of personality. Correlational and principal factor analyses were conducted to assess the relations between the Dark Triad and SPI traits. Multivariate behavioral genetic model-fitting analyses were also conducted to determine the correlated genetic and/or environmental underpinnings of the observed phenotypic correlations. Participants were 358 monozygotic and 98 same-sex dizygotic adult twin pairs from North America. As predicted, results revealed significant correlations between the Dark Triad and most SPI traits, and these correlations were primarily attributable to common genetic and non-shared environmental factors, except in the case of Machiavellianism, where shared environmental effects emerged. Three correlated factors were extracted during joint factor analysis of the Dark Triad and SPI traits, as well as a heritable general factor of personality - results that clarified the structure of the Dark Triad construct. It is concluded that the Dark Triad represents an exploitative and antisocial construct that extends beyond the Big Five model and shares a theoretical space with the SPI traits.

  6. Origin and molecular organization of supernumerary chromosomes of Prochilodus lineatus (characiformes, prochilodontidae) obtained by DNA probes.

    Science.gov (United States)

    Voltolin, Tatiana Aparecida; Laudicina, Alejandro; Senhorini, José Augusto; Bortolozzi, Jehud; Oliveira, Cláudio; Foresti, Fausto; Porto-Foresti, Fábio

    2010-12-01

    In Prochilodus lineatus B-chromosomes are visualized as reduced size extra elements identified as microchromosomes and are variable in morphology and number. We describe the specific total probe (B-chromosome probe) in P. lineatus obtained by chromosome microdissection and a whole genomic probe (genomic probe) from an individual without B-chromosome. The specific B-chromosome was scraped and processed to obtain DNA with amplification by DOP-PCR, and so did the genomic probe DNA. Fluorescence in situ hybridization using the B-chromosome probe labeled with dUTP-Tetramethyl-rhodamine and the genomic probe labeled with digoxigenin-FITC permitted to establish that in this species supernumerary chromosomes with varying number and morphology had different structure of chromatin when compared to that of the regular chromosomes or A complement, since only these extra elements were labeled in the metaphases. The present findings suggest that modifications in the chromatin structure of B-chromosomes to differentiate them from the A chromosomes could occur along their dispersion in the individuals of the population.

  7. An EMG Interface for the Control of Motion and Compliance of a Supernumerary Robotic Finger

    Directory of Open Access Journals (Sweden)

    Irfan Hussain

    2016-11-01

    Full Text Available In this paper, we present an electromyographic (EMG control interface for a supernumerary robotic finger. This novel wearable robot can be used to compensate the missing grasping abilities in chronic stroke patients or to augment human healthy hand so to enhance its grasping capabilities and workspace. The proposed EMG interface controls the motion of the robotic extra finger and its joint compliance. In particular, we use a commercial EMG armband for gesture recognition to be associated with the motion control of the robotic device and surface one channel EMG electrodes interface to regulate the compliance of the robotic device. We also present an updated version of a robotic extra finger where the adduction/abduction motion is realized through ball bearing and spur gears mechanism. We validated the proposed interface with two sets of experiments related to compensation and augmentation. In the first set of experiments, different bi-manual tasks have been performed with the help of the robotic device and simulating a paretic hand. In the second set, the robotic extra finger is used to enlarge the workspace and manipulation capability of healthy hands. In both the sets, the same EMG control interface has been used. The obtained results demonstrate that the proposed control interface is intuitive and can successfully be used for both compensation and augmentation purposes. The proposed approach can be exploited also for the control of different wearable devices that has to actively cooperate with the human limbs.

  8. Array comparative genomic hybridization analysis of small supernumerary marker chromosomes in human infertility.

    Science.gov (United States)

    Guediche, N; Tosca, L; Kara Terki, A; Bas, C; Lecerf, L; Young, J; Briand-Suleau, A; Tou, B; Bouligand, J; Brisset, S; Misrahi, M; Guiochon-Mantel, A; Goossens, M; Tachdjian, G

    2012-01-01

    Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by conventional banding cytogenetics. This study describes four patients with sSMC in relation with infertility. Patient 1 had primary infertility. His brother, fertile, carried the same sSMC (patient 2). Patient 3 presented polycystic ovary syndrome and patient 4 primary ovarian insufficiency. Cytogenetic studies, array comparative genomic hybridization (CGH) and sperm analyses were compared with cases previously reported. sSMC corresponded to the 15q11.2 region (patients 1 and 2), the centromeric chromosome 15 region (patient 3) and the 21p11.2 region (patient 4). Array CGH showed 3.6-Mb gain for patients 1 and 2 and 0.266-Mb gain for patient 4. Sperm fluorescent in-situ hybridization analyses found ratios of 0.37 and 0.30 of sperm nuclei with sSMC(15) for patients 1 and 2, respectively (P < 0.001). An increase of sperm nuclei with disomy X, Y and 18 was noted for patient 1 compared with control and patient 2 (P < 0.001). Among the genes mapped in the unbalanced chromosomal regions, POTE B and BAGE are related to the testis and ovary, respectively. The implication of sSMC in infertility could be due to duplication, but also to mechanical effects perturbing meiosis.

  9. A clinical, cytogenetic, FISH and molecular study of supernumerary marker 15 chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Dennis, N.R. [Princess Anne Hospital, Southampton (United Kingdom); Crolla, J.A.; Harvey, J.F. [Salisbury District Hospital (United Kingdom)

    1994-09-01

    We studied 17 patients with supernumerary marker chromosomes shown by fluorescent in situ hybridization (FISH) with the 15-centromere specific probe pTRA-25 to be 15-derived. Genetic constitution of the marker chromosomes was investigated using FISH, Southern blot analysis and PCR for proximal and distal loci on 15q as well as conventional cytogenetics. Eight of the 17 patients were mentally retarded. Six of the eight carried a de novo marker 15 containing one or two doses of loci known to be in or near the Prader-Willi/Angelman (PWS/AS) region, whereas none of the nine non-retarded patients had duplications of this region, and only two of the eight whose parents were available had a de novo marker. None of the mentally retarded patients had PWS or AS. In two retarded patients (one de novo, one familial) there was no duplication of the PWS/AS region. Uniparental disomy affecting the normal 15 homologs was excluded in 10 of the patients, including all eight with mental retardation.

  10. Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning

    Science.gov (United States)

    Wolf, Benita; Diop, Fodé; Ferraris, Pauline; Wichit, Sineewanlaya; Busso, Coralie; Missé, Dorothée

    2017-01-01

    Zika virus (ZIKV) causes congenital microcephaly. Although ZIKV can impair cell cycle progression and provoke apoptosis, which probably contributes to disease aetiology through depletion of neural progenitor cells, additional cellular mechanisms may be important. Here, we investigated whether ZIKV infection alters centrosome number and spindle positioning, because such defects are thought to be at the root of inherited primary autosomal recessive microcephaly (MCPH). In addition to HeLa cells, in which centrosome number and spindle positioning can be well monitored, we analysed retinal epithelial cells (RPE-1), as well as brain-derived microglial (CHME-5) and neural progenitor (ReN) cells, using immunofluorescence. We established that ZIKV infection leads to supernumerary foci containing centriolar proteins that in some cases drive multipolar spindle assembly, as well as spindle positioning defects in HeLa, RPE-1 and CHME-5 cells, but not in ReN cells. We uncovered similar phenotypes in HeLa cells upon infection with dengue virus (DENV-2), another flavivirus that does not target brain cells and does not cause microcephaly. We conclude that infection with Flaviviridae can increase centrosome numbers and impair spindle positioning, thus potentially contributing to microcephaly in the case of Zika. PMID:28100662

  11. Clinical impact of somatic mosaicism in cases with small supernumerary marker chromosomes.

    Science.gov (United States)

    Liehr, T; Klein, E; Mrasek, K; Kosyakova, N; Guilherme, R S; Aust, N; Venner, C; Weise, A; Hamid, A B

    2013-01-01

    Somatic mosaicism is present in slightly more than 50% of small supernumerary marker chromosome (sSMC) carriers. Interestingly, non-acrocentric derived sSMC show mosaicism much more frequently than acrocentric ones. sSMC can be present in different mosaic rates, which may go below 5% of the studied cells. Also cryptic mosaicism can be present and mosaics may be differently expressed in different tissues of the body. Even though in the overwhelming majority of the cases somatic sSMC mosaicism has no direct clinical effect, there are also cases with altered clinical outcomes due to mosaicism. Also clinically important is the fact that a de novo sSMC, even present in mosaic, may be a hint of uniparental disomy (UPD). As it is under discussion to possibly replace standard karyotyping by methods like array-CGH, the impracticality of the latter to detect low-level sSMC mosaics and/or UPD has to be considered as well. Overall, sSMC mosaicism has to be studied carefully in each individual case, as it can be extremely informative and of importance, especially for prenatal genetic counseling.

  12. Three Supernumerary Marker Chromosomes in a Patient with Developmental Delay, Mental Retardation, and Dysmorphic Features

    Directory of Open Access Journals (Sweden)

    Jie Hu

    2011-01-01

    Full Text Available We characterized three supernumerary marker chromosomes (SMCs simultaneously present in a 2-year- and 10-month-old male patient with mental retardation and dysmorphic features. Peripheral blood chromosome analysis revealed two to three SMCs in 25/26 cells analyzed. The remaining one cell had one SMC. Microarray comparative genomic hybridization (aCGH showed mosaicism for gains of 5q35.3, 15q11.2q13.3, and 18p11.21q11.1 regions. All three gains contain multiple OMIM genes. FISH studies indicated that one of the SMCs is a dicentric ring 15 with two copies of the 15q11.2q13.3 region including SNRPN/UBE3A and two copies of the 5q35.3 region. One of the der(18s contains the 18 centromere and 18p11.2 regions, while the other der(18 has a signal for the 18 centromere only. The phenotype of the patient is compared with that of patients with tetrasomy 15q11.2q13.3, trisomy 5q35.3, and trisomy 18p11.2. Our study demonstrates that aCGH and FISH analyses are powerful tools, which complement the conventional cytogenetic analysis for the identification of SMCs.

  13. Multiple, supernumerary retained teeth in the course of cleido-cranial dysplasia. A case report.

    Science.gov (United States)

    Lewandowski, Bogumił; Martula-Gala, Katarzyna; Brodowski, Robert; Zych, Barbara

    2015-01-01

    Cleido-cranial dysplasia, often referred to as Scheuthauer-Marie-Sainton syndrome, is an autosomal dominant disorder of the musculo-skeletal system. Patients with cleido-cranial dysplasia are characterized by short stature, frequent varus or valgus hip, kyphoscoliosis, underdevelopment of the scapulas and the sternum, incorrect number of ribs. The most characteristic feature is unilateral or bilateral, partial or total underdevelopment of clavicles. Mental development is not affected in this syndrome. Malocclusion, occlusal irregularities, multiple supernumerary teeth, impacted teeth, and persistent milk teeth are found in the stomatognathic system. Teeth often have abnormal anatomy. Gothic palate, cleft hard and soft palate are diagnosed. The aim of this paper is to present a case of a 12-year-old boy diagnosed with irregularities in the masticatory system involving an additional number of retained teeth. The boy was referred by an orthodontist for surgical and orthodontic team therapy. The case presented confirms the observations of other authors that only the multi-specialty collaboration of a pediatrician, a geneticist, an orthopedist, an orthodontist, a maxillofacial surgeon, an implant prosthetic surgeon and a physiotherapist can provide proper diagnosis and treatment.

  14. Human ring chromosomes and small supernumerary marker chromosomes-do they have telomeres?

    Science.gov (United States)

    Guilherme, Roberta Santos; Klein, Elisabeth; Venner, Claudia; Hamid, Ahmed B; Bhatt, Samarth; Melaragno, Maria Isabel; Volleth, Marianne; Polityko, Anna; Kulpanovich, Anna; Kosyakova, Nadezda; Liehr, Thomas

    2012-10-01

    Ring chromosomes and small supernumerary marker chromosomes (sSMC) are enigmatic types of derivative chromosomes, in which the telomeres are thought to play a crucial role in their formation and stabilization. Considering that there are only a few studies that evaluate the presence of telomeric sequences in ring chromosomes and on sSMC, here, we analyzed 14 ring chromosomes and 29 sSMC for the presence of telomeric sequences through fluorescence in situ hybridization (FISH). The results showed that ring chromosomes can actually fall into two groups: the ones with or without telomeres. Additionally, telomeric signals were detectable at both ends of centric and neocentric sSMC with inverted duplication shape, as well as in complex sSMC. Apart from that, generally both ring- and centric minute-shaped sSMC did not present telomeric sequences neither detectable by FISH nor by a second protein-directed immunohistochemical approach. However, the fact that telomeres are absent does not automatically mean that the sSMC has a ring shape, as often deduced in the previous literature. Overall, the results obtained by FISH studies directed against telomeres need to be checked carefully by other approaches.

  15. Clinical management of a fused mandibular lateral incisor with supernumerary tooth: A case report

    Directory of Open Access Journals (Sweden)

    Seda Aydemir

    2016-01-01

    Full Text Available The purpose of this report is to present a rare case of a fused mandibular lateral incisor with supernumerary tooth with a follow-up for 18-months. A 35-year-old female patient was referred to our clinic with an extraoral sinus tract in the chin. The intraoral diagnosis revealed the fusion of her mandibular lateral incisors. Vitality pulp tests were negative for mandibular right central and lateral incisors. Radiographic examinations showed a fused tooth with two separate pulp chambers, two distinct roots, and two separate root canals. There were also periapical lesion of fused teeth and mandibular right central incisor, so endodontic treatment was carried out the related teeth. Radiographic examination revealed a complete healing of the lesion postoperatively at the end of 18-months. This paper reports the successful endodontic and restorative treatment of unilateral fused incisors. Because of the abnormal morphology of the crown and the complexity of the root canal system in fused teeth, treatment protocols require special attention.

  16. Ownership and Agency of an Independent Supernumerary Hand Induced by an Imitation Brain-Computer Interface.

    Directory of Open Access Journals (Sweden)

    Luke Bashford

    Full Text Available To study body ownership and control, illusions that elicit these feelings in non-body objects are widely used. Classically introduced with the Rubber Hand Illusion, these illusions have been replicated more recently in virtual reality and by using brain-computer interfaces. Traditionally these illusions investigate the replacement of a body part by an artificial counterpart, however as brain-computer interface research develops it offers us the possibility to explore the case where non-body objects are controlled in addition to movements of our own limbs. Therefore we propose a new illusion designed to test the feeling of ownership and control of an independent supernumerary hand. Subjects are under the impression they control a virtual reality hand via a brain-computer interface, but in reality there is no causal connection between brain activity and virtual hand movement but correct movements are observed with 80% probability. These imitation brain-computer interface trials are interspersed with movements in both the subjects' real hands, which are in view throughout the experiment. We show that subjects develop strong feelings of ownership and control over the third hand, despite only receiving visual feedback with no causal link to the actual brain signals. Our illusion is crucially different from previously reported studies as we demonstrate independent ownership and control of the third hand without loss of ownership in the real hands.

  17. Unusual small supernumerary marker chromosome (sSMC) 9 in a Klinefelter patient.

    Science.gov (United States)

    Liehr, T; Mrasek, K; Starke, H; Claussen, U; Schreiber, G

    2005-01-01

    Small supernumerary marker chromosomes (sSMC) are small additional chromosomes characterizable for their origin only by molecular cytogenetic approaches. sSMC have been reported previously in four types of syndromes associated with chromosomal imbalances: in approximately 150 cases with Turner syndrome, 26 cases with Down syndrome and only one case each with Klinefelter syndrome and "Triple-X"-syndrome. Here we report the second case with an sSMC detected in addition to a Klinefelter karyotype. Molecular cytogenetics applying centromere-specific multicolor FISH (cenM-FISH) and a specific subcentromere-specific (subcenM-FISH) probe set characterized the sSMC as a dic(9)(:p12-->q11.1::q11.1--> p11.1:). The reported patient was described with hypogonadism, gynaecomastia plus a bronchial carcinoma. The patient's clinical features are discussed in connection with other Klinefelter cases and possible consequences of presence of the sSMC(9). Furthermore, a suggestion is made for the mode of sSMC-formation in this case.

  18. Supernumerary marker chromosomes derived from chromosome 6: cytogenetic, molecular cytogenetic, and array CGH characterization.

    Science.gov (United States)

    Huang, Bing; Pearle, Phyllis; Rauen, Katherine A; Cotter, Philip D

    2012-07-01

    Supernumerary marker chromosomes (SMC) are relatively common in prenatal diagnosis. As the clinical outcomes vary greatly, a better understanding of the karyotype-phenotype correlation for different SMCs will be important for genetic counseling. We present two cases of prenatally detected de novo, small SMCs. The markers were present in 80% of amniocyte colonies in Case 1 and 38% of the colonies in Case 2. The SMCs were determined to be derived from chromosome 6 during postnatal confirmation studies. Although the sizes and the chromosomal origin of the SMCs in these two cases appeared to be similar, the clinical outcomes varied. The clinical manifestations observed in Case 1 included small for gestational age, feeding difficulty at birth, hydronephrosis, deviated septum and dysmorphic features, while the phenotype is apparently normal in Case 2. Array comparative genomic hybridization (CGH) was performed and showed increase in dosage for approximately 26 Mb of genetic material from the proximal short and long arms of chromosome 6 in Case 1. Results of array CGH were uninformative in Case 2, either due to mosaicism or lack of detectable euchromatin. The difference in the clinical presentation in these two patients may have resulted from the difference in the actual gene contents of the marker chromosomes and/or the differential distribution of the mosaicism.

  19. Characteristics and sequelae of erupted supernumerary teeth: A study of 218 cases among Sri Lankan children.

    Science.gov (United States)

    Herath, Chandra; Jayawardena, Chantha; Nagarathne, Nandani; Perera, Kanthi

    2016-12-19

    In the present study, we investigated the characteristics and sequelae of erupted supernumerary teeth (ST) in a sample of Sri Lankan children. Data were recorded from patients' clinical records, radiographs, models, and extracted teeth. The sample consisted of 239 ST from 218 patients. The mean age of the sample was 9.08 ± 2.47 years. The male-to-female ratio was 2.8:1. The majority (42.66%) of patients with ST were in aged 8-10 years. Many (94.94%) of the ST were located in the premaxilla (incisor), followed by the canine (4.22%), premolar (0.42%), and molar (0.42%) regions. The most common shape of ST teeth was conical. Malocclusion (59.83%) was the major problem associated with ST, and the clinical impact was highest on the 8-10-year age group. A strong association was observed between patients' age and clinical impact to the dentition (χ(2) =42.09, P=.000). Because the majority of ST can lead to malocclusion, especially in mixed dentition, awareness, early detection, and timely clinical intervention of ST are recommended. © 2016 John Wiley & Sons Australia, Ltd.

  20. Clinical management of a fused mandibular lateral incisor with supernumerary tooth: A case report

    Science.gov (United States)

    Aydemir, Seda; Ozel, Emre; Arukaslan, Goze; Tekce, Neslihan

    2016-01-01

    The purpose of this report is to present a rare case of a fused mandibular lateral incisor with supernumerary tooth with a follow-up for 18-months. A 35-year-old female patient was referred to our clinic with an extraoral sinus tract in the chin. The intraoral diagnosis revealed the fusion of her mandibular lateral incisors. Vitality pulp tests were negative for mandibular right central and lateral incisors. Radiographic examinations showed a fused tooth with two separate pulp chambers, two distinct roots, and two separate root canals. There were also periapical lesion of fused teeth and mandibular right central incisor, so endodontic treatment was carried out the related teeth. Radiographic examination revealed a complete healing of the lesion postoperatively at the end of 18-months. This paper reports the successful endodontic and restorative treatment of unilateral fused incisors. Because of the abnormal morphology of the crown and the complexity of the root canal system in fused teeth, treatment protocols require special attention. PMID:26962321

  1. Unexpected structural complexity of supernumerary marker chromosomes characterized by microarray comparative genomic hybridization

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    Hing Anne V

    2008-04-01

    Full Text Available Abstract Background Supernumerary marker chromosomes (SMCs are structurally abnormal extra chromosomes that cannot be unambiguously identified by conventional banding techniques. In the past, SMCs have been characterized using a variety of different molecular cytogenetic techniques. Although these techniques can sometimes identify the chromosome of origin of SMCs, they are cumbersome to perform and are not available in many clinical cytogenetic laboratories. Furthermore, they cannot precisely determine the region or breakpoints of the chromosome(s involved. In this study, we describe four patients who possess one or more SMCs (a total of eight SMCs in all four patients that were characterized by microarray comparative genomic hybridization (array CGH. Results In at least one SMC from all four patients, array CGH uncovered unexpected complexity, in the form of complex rearrangements, that could have gone undetected using other molecular cytogenetic techniques. Although array CGH accurately defined the chromosome content of all but two minute SMCs, fluorescence in situ hybridization was necessary to determine the structure of the markers. Conclusion The increasing use of array CGH in clinical cytogenetic laboratories will provide an efficient method for more comprehensive characterization of SMCs. Improved SMC characterization, facilitated by array CGH, will allow for more accurate SMC/phenotype correlation.

  2. Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion

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    Ren Song

    2016-02-01

    Full Text Available Infection by alphaherpesviruses, including herpes simplex virus (HSV and pseudorabies virus (PRV, typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS. Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs. The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β or gamma interferon (IFN-γ significantly diminished the number of herpes simplex virus 1 (HSV-1 and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1 only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion.

  3. Mitochondria Localize to Injured Axons to Support Regeneration.

    Science.gov (United States)

    Han, Sung Min; Baig, Huma S; Hammarlund, Marc

    2016-12-21

    Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo, single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons so that average mitochondria density increases after injury. Moreover, single-neuron analysis reveals that axons that fail to increase mitochondria have poor regeneration. Experimental alterations to axonal mitochondrial distribution or mitochondrial respiratory chain function result in corresponding changes to regeneration outcomes. Axonal mitochondria are specifically required for growth-cone migration, identifying a key energy challenge for injured neurons. Finally, mitochondrial localization to the axon after injury is regulated in part by dual-leucine zipper kinase 1 (DLK-1), a conserved regulator of axon regeneration. These data identify regulation of axonal mitochondria as a new cell-biological mechanism that helps determine the regenerative response of injured neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Motor and dorsal root ganglion axons serve as choice points for the ipsilateral turning of dI3 axons.

    Science.gov (United States)

    Avraham, Oshri; Hadas, Yoav; Vald, Lilach; Hong, Seulgi; Song, Mi-Ryoung; Klar, Avihu

    2010-11-17

    The axons of the spinal intersegmental interneurons are projected longitudinally along various funiculi arrayed along the dorsal-ventral axis of the spinal cord. The roof plate and the floor plate have a profound role in patterning their initial axonal trajectory. However, other positional cues may guide the final architecture of interneuron tracks in the spinal cord. To gain more insight into the organization of specific axonal tracks in the spinal cord, we focused on the trajectory pattern of a genetically defined neuronal population, dI3 neurons, in the chick spinal cord. Exploitation of newly characterized enhancer elements allowed specific labeling of dI3 neurons and axons. dI3 axons are projected ipsilaterally along two longitudinal fascicules at the ventral lateral funiculus (VLF) and the dorsal funiculus (DF). dI3 axons change their trajectory plane from the transverse to the longitudinal axis at two novel checkpoints. The axons that elongate at the DF turn at the dorsal root entry zone, along the axons of the dorsal root ganglion (DRG) neurons, and the axons that elongate at the VLF turn along the axons of motor neurons. Loss and gain of function of the Lim-HD protein Isl1 demonstrate that Isl1 is not required for dI3 cell fate. However, Isl1 is sufficient to impose ipsilateral turning along the motor axons when expressed ectopically in the commissural dI1 neurons. The axonal patterning of dI3 neurons, revealed in this study, highlights the role of established axonal cues-the DRG and motor axons-as intermediate guidepost cues for dI3 axons.

  5. Axon Membrane Skeleton Structure is Optimized for Coordinated Sodium Propagation

    CERN Document Server

    Zhang, Yihao; Li, He; Tzingounis, Anastasios V; Lykotrafitis, George

    2016-01-01

    Axons transmit action potentials with high fidelity and minimal jitter. This unique capability is likely the result of the spatiotemporal arrangement of sodium channels along the axon. Super-resolution microscopy recently revealed that the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under entropic tension. Sodium channels also exhibit a periodic distribution pattern, as they bind to ankyrin G, which associates with spectrin. Here, we elucidate the relationship between the axon membrane skeleton structure and the function of the axon. By combining cytoskeletal dynamics and continuum diffusion modeling, we show that spectrin filaments under tension minimize the thermal fluctuations of sodium channels and prevent overlap of neighboring channel trajectories. Importantly, this axon skeletal arrangement allows for a highly reproducible band-like activation of sodium channels leading to coordinated sodium propagation along the axon.

  6. Axon degeneration: make the Schwann cell great again

    Directory of Open Access Journals (Sweden)

    Keit Men Wong

    2017-01-01

    Full Text Available Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration (WD, which occurs after acute axonal injury. In the peripheral nervous system (PNS, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system (CNS, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well-documented that Schwann cells (SCs have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs 'sense' axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro-degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent findings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.

  7. The pattern of a specimen of Pycnogonum litorale (Arthropoda, Pycnogonida) with a supernumerary leg can be explained with the "boundary model" of appendage formation

    Science.gov (United States)

    Scholtz, Gerhard; Brenneis, Georg

    2016-02-01

    A malformed adult female specimen of Pycnogonum litorale (Pycnogonida) with a supernumerary leg in the right body half is described concerning external and internal structures. The specimen was maintained in our laboratory culture after an injury in the right trunk region during a late postembryonic stage. The supernumerary leg is located between the second and third walking legs. The lateral processes connecting to these walking legs are fused to one large structure. Likewise, the coxae 1 of the second and third walking legs and of the supernumerary leg are fused to different degrees. The supernumerary leg is a complete walking leg with mirror image symmetry as evidenced by the position of joints and muscles. It is slightly smaller than the normal legs, but internally, it contains a branch of the ovary and a gut diverticulum as the other legs. The causes for this malformation pattern found in the Pycnogonum individual are reconstructed in the light of extirpation experiments in insects, which led to supernumerary mirror image legs, and the "boundary model" for appendage differentiation.

  8. Schwann cells-axon interaction in myelination.

    Science.gov (United States)

    Taveggia, Carla

    2016-08-01

    The remarkable interaction between glial cells and axons is crucial for nervous system development and homeostasis. Alterations in this continuous communication can cause severe pathologies that can compromise the integrity of the nervous system. The most dramatic consequence of this interaction is the generation of the myelin sheath, made by myelinating glial cells: Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In this review I will focus on signals coming from axons in the first part and then on those from Schwann cells that promote the formation and the maintenance of peripheral myelin. I will discuss their inter-relationship together with seminal and important advances recently made.

  9. Multifunctional Silk Nerve Guides for Axon Outgrowth

    Science.gov (United States)

    Tupaj, Marie C.

    Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long

  10. Interspecies variation in axon-myelin relationships.

    Science.gov (United States)

    Fraher, J P; O'Sullivan, A W

    2000-01-01

    The primary objective of this paper was to determine the extent and nature of interspecies differences in axon calibre and myelin sheath thickness and in the various relationships between these. Morphometric analysis of the axon perimeter-myelin sheath thickness relationship was performed on an equivalent nerve fibre population in a mammal, the rat, a bird, the chicken, an amphibian, the frog, a bony fish, the trout, and a cartilaginous fish, the dogfish. The abducent nerve was studied. It is especially suitable for this purpose because its fibres are closely similar in type and in peripheral distribution across the species studied. The relationship differed substantially between species. Differences were present in its setting, as described by the positions of the scatterplots, in the g ratio and in the regression and correlation data relating the parameters. Both parameters were markedly larger in the fish species than in all of the others. In addition, in rat, chicken, frog and trout, where large and small fibre classes could be differentiated clearly, the setting of the relationship between the two parameters was different for the two classes. In the main, variation in each of the parameters was greater between than within species. The larger fibres in the fish species were closely similar in axon perimeter and sheath thickness despite their long evolutionary separation. From this study and from others in the series, it may be concluded that there is no fixed or constant relationship between axon calibre and the thickness of the surrounding myelin sheath. Each nerve tends to have its own particular relationship and this differs between species.

  11. Retinoic acid signaling in axonal regeneration

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    Radhika ePuttagunta

    2012-01-01

    Full Text Available Following an acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor β2 (RARß2, to induce axonal regeneration following spinal cord injury (SCI. Recently, it has been shown that in dorsal root ganglia neurons, cAMP levels were greatly increased by lentiviral RARβ2 expression and contributed to neurite outgrowth. Moreover, RARβ agonists, in cerebellar granule neurons and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RARβ-dependent neurite outgrowth. More recently, RA-RARß pathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.

  12. Shh goes multidirectional in axon guidance

    Institute of Scientific and Technical Information of China (English)

    Paola Bovolenta; Luisa Sanchez-Arrones

    2012-01-01

    Shh and Wnts,secreted by the floor and roof plate of the spinal cord,direct longitudinal growth of the axons from the adjacent ventral funiculus and cortico-spinal tract.Whether these midline cues influencethe directionality of axons elongating in more lateral positions of the spinal cord is unexplored.Song and colleagues investigate this possibility and demonstrate that the location of descending raphe-spinal tract in the ventrolateral spinal cord is dictated by the simultaneous repellent activity of Shh gradients in both the anteriorto-posterior (A-P) and medial-tolateral (M-L) axis. The spinal cord is the main pathway for exchange of information between the brain and the rest of the body.Sensory information collected in the body periphery is conveyed to the brain by axonal tracts that ascend along the spinal cord whereas motor information travels from the brain to the periphery in descending tracts.Precise spatial organization of these fiber tracts is thus essential for animal behavior and survival.

  13. Where does slow axonal transport go?

    Science.gov (United States)

    Terada, Sumio

    2003-12-01

    Axonal transport is the specialized and well-developed intracellular transport system for regulated and/or long-distance transport based on generalized cellular machineries. Among them, slow axonal transport conveys cytoplasmic proteins. The motor molecule, the nature of transporting complex and the transport regulation mechanism for slow transport are still unclarified. There has been a dispute regarding the nature of transporting complex of cytoskeletal proteins, polymer-sliding hypothesis versus subunit-transport theory. Recent data supporting the hypothesis of polymer sliding in cultured neurons only reconfirm the previously reported structure and this inference suffers from the lack of ultrastructural evidence and the direct relevance to the physiological slow transport phenomenon in vivo. Observation of the moving cytoskeletal proteins in vivo using transgenic mice or squid giant axons revealed that subunits do move in a microtubule-dependent manner, strongly indicating the involvement of microtubule-based motor kinesin. If the slow transport rate reflects the intermittent fast transport dependent on kinesin motor, we have to investigate the molecular constituents of the transporting complex in more detail and evaluate why the motor and cargo interaction is so unstable. This kind of weak and fluctuating interaction between various molecular pairs could not be detected by conventional techniques, thus necessitating the establishment of a new experimental system before approaching the molecular regulation problem.

  14. Synaptic Democracy and Vesicular Transport in Axons

    Science.gov (United States)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  15. Efferent axons in the avian auditory nerve.

    Science.gov (United States)

    Köppl, C

    2001-05-01

    The sensory hair cells of the inner ear receive both afferent and efferent innervation. The efferent supply to the auditory organ has evolved in birds and mammals into a separate complex system, with several types of neurons of largely unknown function. In this study, the efferent axons in four different species of birds (chicken, starling, barn owl and emu) were examined anatomically. Total numbers of efferents supplying the cochlear duct (auditory basilar papilla and the vestibular lagenar macula) were determined; separate estimates of the efferents to the lagenar macula only were also derived and subtracted. The numbers for auditory efferents thus varied between 120 (chicken) and 1068 (barn owl). Considering the much larger numbers of hair cells in the basilar papilla, each efferent is predicted to branch extensively. However, pronounced species-specific differences as well as regional differences along the tonotopic gradient of the basilar papilla were documented. Myelinated and unmyelinated axons were found, with mean diameters of about 1 microm and about 0.5 microm, respectively. This suggests two basic populations of efferents, however, they did not appear to be distinguished sharply. Evidence is presented that some efferents lose their myelination at the transition from central oligodendrocyte to peripheral Schwann cell myelin. Finally, a comparison of the four bird species evaluated suggests that the efferent population with smaller, unmyelinated axons is the phylogenetically more primitive one. A new population probably arose in parallel with the evolution and differentiation of the specialized hair-cell type it innervates, the short hair cell.

  16. MRI of the diffuse axonal injury

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    Joo, Yang Gu; Woo, Young Hoon; Suh, Soo Jhi [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    1992-01-15

    CT has facilitated early recognition and treatment of focal brain injuries in patients with head trauma. However, CT shows relatively low sensitivity in identifying non hemorrhage contusion and injuries of white matter. MR is known to be superior to CT in detection of white matter injuries, such as diffuse axonal injury. MR imaging in 14 cases of diffuse axonal injury on 2.0T was studied. The corpus callosum, especially the body portion, was the most commonly involved site. The lesions ranged from 5 to 20mm in size with ovoid to elliptical shape. T2WI was the most sensitive pulse sequence in detecting lesions such as white matter degeneration, hemorrhagic and non hemorrhagic contusion. The lesions were nonspecific as high and low signal intensities on T2WI and T1WI respectively. CT showed white matter abnormality in only 1 case of 14 cases. We propose MR imaging as the primary imaging procedure for the detection of diffuse axonal injury because of its multiplanar capabilities and higher sensitivity.

  17. Axon-glial relations during regeneration of axons in the adult rat anterior medullary velum.

    Science.gov (United States)

    Berry, M; Hunter, A S; Duncan, A; Lordan, J; Kirvell, S; Tsang, W L; Butt, A M

    1998-12-01

    The anterior medullary velum (AMV) of adult Wistar rats was lesioned in the midsagittal plane, transecting all decussating axons including those of the central projection of the IVth nerve. At selected times up to 200 days after transection, the degenerative and regenerative responses of axons and glia were analyzed using transmission and scanning electron microscopy and immunohistochemistry. In particular, both the capacity of oligodendrocytes to remyelinate regenerated fibers and the stability of the CNS/PNS junctional zone of the IVth nerve rootlet were documented. Transected central AMV axons exhibited four patterns of fiber regeneration in which fibers grew: rostrocaudally in the reactive paralesion neuropil (Group 1); randomly within the AMV (Group 2); into the ipsilateral IVth nerve rootlet, after turning at the lesion edge and growing recurrently through the old degenerated contralateral central trochlear nerve trajectory (Group 3); and ectopically through paralesion tears in the ependyma onto the surface of the IVth ventricle (Group 4). Group 1-3 axons regenerated unperturbed through degenerating central myelin, reactive astrocytes, oligodendrocytes, microglia, and large accumulations of hematogenous macrophages. Only Group 3 axons survived long term in significant numbers, and all became myelinated by oligodendrocytes, ultimately establishing thin sheaths with relatively normal nodal gaps and intersegmental myelin sheath lengths. Schwann cells at the CNS/PNS junction of the IVth nerve rootlet did not invade the CNS, but astrocyte processes grew across the junction into the PNS portion of the IVth nerve. The basal lamina of the junctional glia limitans remained stable throughout the experimental period.

  18. Supernumerary breast. A case Presentation Mama supernumeraria. Presentación de un caso

    Directory of Open Access Journals (Sweden)

    Juan Miguel Guerra Cabrera

    2010-07-01

    Full Text Available Congenital malformations of the breast appear in 10 % of the population. The existence of mammary tissue at any line of the breast is classified according to Kajava’s categories into eight classes which differ one from the other in the presence or absence of the areola of the breast, nipple and glandular tissue. This report presents a case of a puerpera who had delivered her child seven days before her attendance to hospital. She presented with discharge from her both axillae. On physical examination, a supernumerary nipple with milky secretion out from it was found in her right axilla and secretion throughout the contralateral axilla through the skin pores, with absence of nipple and areola in that axillary region. The echographic study revealed the presence of bilateral ectopic mammary tissue. This case belongs to Kajava’s class IV classification in the left axilla and a variery of Type I in the right axilla. In facing a mammary malformation, a conservative attitude seems to be the most appropriate although esthetics requires surgery. To keep into account the presence of supernumerary breasts will be a need for the prevention of breast cancer. This case has been presented due to all these reasons and the unusual features of this case.Las malformaciones congénitas de la mama aparecen hasta en un 10 % de la población. La existencia de tejido mamario en algún punto de las líneas mamarias se clasifica, según Kajava, en 8 clases, que se diferencian por la presencia o no de areola mamaria, pezón y tejido glandular. Se presenta el caso de una paciente con secreción por ambas axilas en su séptimo día de puerperio. En la exploración se detectó un pezón supernumerario en axila derecha con secreción láctea a través de este y secreción a través de la axila contra lateral por los poros de la piel, con ausencia de pezón y de areola. El estudio ecográfico demostró la presencia de tejido mamario ectópico bilateral. Este caso pertenece

  19. Supernumerary registrar experience at the University of Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    S Peer

    2017-01-01

    Full Text Available Background. Despite supernumerary registrars (SNRs being hosted in South African (SA training programmes, there are no reports of their experience. Objectives. To evaluate the experience of SNRs at the University of Cape Town, SA, and the experience of SNRs from the perspective of SA registrars (SARs. Methods. SNRs and SARs completed an online survey in 2012. Results. Seventy-three registrars responded; 42 were SARs and 31 were SNRs. Of the SNRs 47.8% were self-funded, 17.4% were funded through private organisations, and 34.8% were funded by governments. Average annual income was ZAR102 349 (range ZAR680 - 460 000. Funding was considered insufficient by 61.0%. Eighty-seven percent intended to return to their home countries. Personal sacrifices were deemed worthwhile from academic (81.8% and social (54.5% perspectives, but not financially (33.3%. Only a small majority were satisfied with the orientation provided and with assimilation into their departments. Almost half experienced challenges relating to cultural and social integration. Almost all SARs supported having SNRs. SNRs reported xenophobia from patients (23.8% and colleagues (47.8%, and felt disadvantaged in terms of learning opportunities, academic support and on-call allocations. Conclusions. SNRs are fee-paying students and should enjoy academic and teaching support equal to that received by SARs. Both the university and the teaching hospitals must take steps to improve the integration of SNRs and ensure that they receive equal access to academic support and clinical teaching, and also need to take an interest in their financial wellbeing. Of particular concern are perceptions of xenophobia from SA medical colleagues.

  20. Small supernumerary marker chromosomes (sSMC in humans; are there B chromosomes hidden among them

    Directory of Open Access Journals (Sweden)

    Ogilvie Caroline

    2008-06-01

    Full Text Available Abstract Background Small supernumerary marker chromosomes (sSMC and B-chromosomes represent a heterogeneous collection of chromosomes added to the typical karyotype, and which are both small in size. They may consist of heterochromatic and/or euchromatic material. Also a predominance of maternal transmission was reported for both groups. Even though sSMC and B-chromosomes show some similarity it is still an open question if B-chromosomes are present among the heterogeneous group of sSMC. According to current theories, sSMC would need drive, drift or beneficial effects to increase in frequency in order to become B chromosome. However, up to now no B-chromosomes were described in human. Results Here we provide first evidence and discuss, that among sSMC B-chromosomes might be hidden. We present two potential candidates which may already be, or may in future evolve into B chromosomes in human: (i sSMC cases where the marker is stainable only by DNA derived from itself; and (ii acrocentric-derived inverted duplication sSMC without associated clinical phenotype. Here we report on the second sSMC stainable exclusively by its own DNA and show that for acrocentric derived sSMC 3.9× more are familial cases than reported for other sSMC. Conclusion The majority of sSMC are not to be considered as B-chromosomes. Nonetheless, a minority of sSMC show similarities to B-chromosomes. Further studies are necessary to come to final conclusions for that problem.

  1. Esthetic and endodontic management of fused maxillary lateral incisor and supernumerary teeth with all ceramic restoration after trauma

    Directory of Open Access Journals (Sweden)

    Kiranmeet Kaur Khurana

    2014-01-01

    Full Text Available Double or fusion of the teeth is a primary developmental anomaly union of two independently developing primary or permanent teeth. The tooth fusion may contribute to various significant problems such as crowding, caries and periodontal diseases. Fused teeth require an interdisciplinary approach combining the endodontic, esthetic and prosthetic treatments. All ceramic restoration meets the requirement of better appearance, biocompatibility and long life. By using restorative therapy esthetic and functional criteria were satisfied. Management of a case of fusion of a maxillary lateral incisor and a supernumerary tooth is presented.

  2. Supernumerary teeth and pseudarthrosis of the mandible in a young male from the mediaeval cemetery in Stenjevec

    Directory of Open Access Journals (Sweden)

    Željka Bedić

    2010-06-01

    Full Text Available Anthropological analysis of a young adult male from the mediaeval Stenjevec skeletal series revealed supernumerary teeth on both sides of the mandible, and an un-united subcondylar fracture of the mandible. The first condition is a developmental abnormality, while subcondylar fractures are one of the most frequent fractures of the mandible. Although, the osteological collection of the Department of Archaeology of the Croatian academy of Sciences and Arts consists of nearly 5,500 skeletons, this is the first documented case that exhibits these conditions in Croatian archaeological skeletal series.

  3. Multiple Impacted Permanent and Supernumerary Teeth in the Anterior Mandible of Nonsyndromic Case: A Systematic Review and Multidisciplinary Approach to Management

    Directory of Open Access Journals (Sweden)

    Pushkar Gawande

    2015-01-01

    Full Text Available Multiple impacted permanent and supernumerary teeth have been associated with the syndromes and metabolic disorders. Approximately, 75% of all the supernumerary teeth are impacted and are asymptomatic. Consequently, most such teeth constitute casual findings in the context of routine X-ray studies. Lack of eruptive force and rotation of tooth buds may cause multiple impactions, and additional examinations may be necessary to exclude systemic and metabolic conditions. We present a rare nonsyndromic case with 11 multiple impacted teeth in the anterior mandible, with systematic literature review and multidisciplinary management.

  4. Dynamics of axon fasciculation in the presence of neuronal turnover

    CERN Document Server

    Chaudhuri, Debasish; Mohanty, P K; Zapotocky, Martin

    2008-01-01

    We formulate and characterize a model aiming to describe the formation of fascicles of axons mediated by contact axon-axon interactions. The growing axons are represented as interacting directed random walks in two spatial dimensions. To mimic axonal turnover in the mammalian olfactory system, the random walkers are injected and removed at specified rates. In the dynamical steady state, the position-dependent distribution of fascicle sizes obeys a scaling law. We identify several distinct time scales that emerge from the dynamics, are sensitive functions of the microscopic parameters of the model, and can exceed the average axonal lifetime by orders of magnitude. We discuss our findings in terms of an analytically tractable, effective model of fascicle dynamics.

  5. Axon-glia interaction and membrane traffic in myelin formation

    OpenAIRE

    2014-01-01

    In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is...

  6. Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior

    OpenAIRE

    Yang, Dongren; Lauridsen, Holly; Buels, Kalmia; Chi, Lai-Har; La Du, Jane; Bruun, Donald A.; Olson, James R.; Tanguay, Robert L.; Lein, Pamela J.

    2011-01-01

    Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO), or the excreted metabolite trichloro-2-pyridinol (TCP...

  7. A unified cell biological perspective on axon-myelin injury

    OpenAIRE

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin

    2014-01-01

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon–myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a loc...

  8. A unified cell biological perspective on axon-myelin injury.

    Science.gov (United States)

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin

    2014-08-04

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon-myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a local inflammatory disease process early in MS into the global progressive disorder seen during later stages. This mode of spreading could also apply to other neurological disorders.

  9. Axonal autophagy during regeneration of the rat sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Kangrong Lu; Zhongxian Piao; Zhenxi Liu; Weiwang Gu; Wanshan Wang; Nngjie Piao

    2008-01-01

    BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma

  10. Molecular analysis of axon repulsion by the notochord.

    Science.gov (United States)

    Anderson, Christopher N G; Ohta, Kunimasa; Quick, Marie M; Fleming, Angeleen; Keynes, Roger; Tannahill, David

    2003-03-01

    During development of the amniote peripheral nervous system, the initial trajectory of primary sensory axons is determined largely by the action of axon repellents. We have shown previously that tissues flanking dorsal root ganglia, the notochord lying medially and the dermamyotomes lying laterally, are sources of secreted molecules that prevent axons from entering inappropriate territories. Although there is evidence suggesting that SEMA3A contributes to the repellent activity of the dermamyotome, the nature of the activity secreted by the notochord remains undetermined. We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent. Moreover, using a spectrum of different axon populations to assay the notochord activity, together with neuropilin/Fc receptor reagents to block semaphorin activity in collagen gel assays, we show that SEMA3A probably contributes to notochord-mediated repulsion. Sympathetic axons that normally avoid the midline in vivo are also repelled, in part, by a semaphorin-based notochord activity. Although our results implicate semaphorin signalling in mediating repulsion by the notochord, repulsion of early dorsal root ganglion axons is only partially blocked when using neuropilin/Fc reagents. Moreover, retinal axons, which are insensitive to SEMA3A, are also repelled by the notochord. We conclude that multiple factors act in concert to guide axons in this system, and that further notochord repellents remain to be identified.

  11. Crossing the Border: Molecular Control of Motor Axon Exit

    Directory of Open Access Journals (Sweden)

    Arlene Bravo-Ambrosio

    2011-11-01

    Full Text Available Living organisms heavily rely on the function of motor circuits for their survival and for adapting to ever-changing environments. Unique among central nervous system (CNS neurons, motor neurons (MNs project their axons out of the CNS. Once in the periphery, motor axons navigate along highly stereotyped trajectories, often at considerable distances from their cell bodies, to innervate appropriate muscle targets. A key decision made by pathfinding motor axons is whether to exit the CNS through dorsal or ventral motor exit points (MEPs. In contrast to the major advances made in understanding the mechanisms that regulate the specification of MN subtypes and the innervation of limb muscles, remarkably little is known about how MN axons project out of the CNS. Nevertheless, a limited number of studies, mainly in Drosophila, have identified transcription factors, and in some cases candidate downstream effector molecules, that are required for motor axons to exit the spinal cord. Notably, specialized neural crest cell derivatives, referred to as Boundary Cap (BC cells, pre-figure and demarcate MEPs in vertebrates. Surprisingly, however, BC cells are not required for MN axon exit, but rather restrict MN cell bodies from ectopically migrating along their axons out of the CNS. Here, we describe the small set of studies that have addressed motor axon exit in Drosophila and vertebrates, and discuss our fragmentary knowledge of the mechanisms, which guide motor axons out of the CNS.

  12. Corticostriatal combinatorics: the implications of corticostriatal axonal arborizations.

    Science.gov (United States)

    Zheng, T; Wilson, C J

    2002-02-01

    The complete striatal axonal arborizations of 16 juxtacellularly stained cortical pyramidal cells were analyzed. Corticostriatal neurons were located in the medial agranular or anterior cingulate cortex of rats. All axons were of the extended type and formed synaptic contacts in both the striosomal and matrix compartments as determined by counterstaining for the mu-opiate receptor. Six axonal arborizations were from collaterals of brain stem-projecting cells and the other 10 from bilaterally projecting cells with no brain stem projections. The distribution of synaptic boutons along the axons were convolved with the average dendritic tree volume of spiny projection neurons to obtain an axonal innervation volume and innervation density map for each axon. Innervation volumes varied widely, with single axons occupying between 0.4 and 14.2% of the striatum (average = 4%). The total number of boutons formed by individual axons ranged from 25 to 2,900 (average = 879). Within the innervation volume, the density of innervation was extremely sparse but inhomogeneous. The pattern of innervation resembled matrisomes, as defined by bulk labeling and functional mapping experiments, superimposed on a low background innervation. Using this sample as representative of all corticostriatal axons, the total number of corticostriatal neurons was estimated to be 17 million, about 10 times the number of striatal projection neurons.

  13. Fast axonal transport in early experimental disc edema.

    Science.gov (United States)

    Radius, R L; Anderson, D R

    1980-02-01

    Previous work has documented impairment of slow axonal transport in papilledema, but the abnormalities in rapid transport were less certain. Therefore fast axonal transport was studied in 19 primate eyes subjected to ocular hypotony for 6 to 72 hr following surgical fistulization of the anterior chamber. Mild, irregular alterations in fast axonal transport were detected only after nerve head swelling was apparent. These changes in fast transport mechanisms in cases of nerve head edema occur after, and may be secondary to, impaired slow axoplasmic flow and the resultant axonal swelling. Furthermore, since prolonged complete interruption of axonal transport is theoretically inconsistent with the continued normal neuron function characteristic of papilledema and, moreover, since previous data shows a "slowdown" rather than complete blockade of axonal transport in papilledema, it is likely that in eyes with papilledema there does not exist a complete flock of axonal transport. Therefore we hypothesize that the swelling results when slow axoplasmic flow is locally slowed down but not totally stopped, with the axon distention producing secondary mild, irregular changes in fast axonal transport.

  14. Differences in excitability properties of FDI and ADM motor axons.

    Science.gov (United States)

    Bae, Jong Seok; Sawai, Setsu; Misawa, Sonoko; Kanai, Kazuaki; Isose, Sagiri; Kuwabara, Satoshi

    2009-03-01

    The first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength-duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning-test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ.

  15. Histone Acetylation Inhibitors Promote Axon Growth in Adult DRG neurons

    Science.gov (United States)

    Lin, Shen; Nazif, Kutaiba; Smith, Alexander; Baas, Peter W; Smith, George M

    2015-01-01

    Intrinsic mechanisms that guide damaged axons to regenerate following spinal cord injury remain poorly understood. Manipulation of posttranslational modifications of key proteins in mature neurons could re-invigorate growth machinery after injury. One such modification is acetylation, a reversible process controlled by two enzyme families acting in opposition, the Histone Deacetylases (HDACs) and the Histone Acetyl Transferases (HATs). While acetylated histones in the nucleus is associated with upregulation of growth promoting genes, de-acetylated tubulin in the axoplasm is associated with more labile microtubules, conducive to axon growth. In this study we investigated the effects of HAT inhibitors and HDAC inhibitors on cultured adult dorsal root ganglia (DRG) neurons. We found that inhibition of HATs, using Anacardic Acid or CPTH2, improved axon outgrowth, while inhibition of HDACs using TSA or Tubacin, inhibited axon growth. Furthermore, Anacardic Acid increased the number of axons able to cross an inhibitory chondroitin sulfate proteoglycan (CSPG) border. Histone acetylation, but not tubulin acetylation levels, was affected by HAT inhibitors, whereas tubulin acetylation levels were increased in the presence of HDAC inhibitor Tubacin. Although microtubule stabilizing drug taxol did not have an effect on the lengths of DRG axons, nocodazole decreased axon lengths. While the mechanistic basis will require future studies, our data show that inhibitors of HAT can augment axon growth in adult DRG neurons, with the potential of aiding axon growth over inhibitory substrates produced by the glial scar. PMID:25702820

  16. Present status of studies on diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    Jie Ma; Chonggong Zhang; Yi Li

    2006-01-01

    OBJECTIVE: To explain the present status of study on diffuse axonal injury,investigate its pathogenesis and pathophysiological changes ,and suggest principles for the diagnosis and treatment.DATA SOURCES: Articles about diffuse axonal injury published in English from January 1994 to October 2006 were searched in Pubmed database using the keywords of "diffuse axonal injury,pathogenesis,therapy".STUDY SELECTION: The collected articles were primarily screened to select those associated with diffuse axonal injury,the obviously irrelated articles were excluded,and the rest ones were retrieved manually,and the full-texes were searched.DATA EXTRACTION: Totally 98 articles were collected,41 of them were involved.and the other 57 were excluded.DATA SYNTHESIS: Diffuse axonal injury is mainly caused by acceleratory or deceleratory injury,and its pathophysiological change is a progressive duration,local axonal injury finally develops to axonal breakage,mainly includes inactivation of natrium channel,intracellular Ca2+ overloading,activation of calcium protease,caspase etc.,and mitochondrial injury.At present,there is still lack of effective therapeutic methods for diffuse axonal injury,so we should actively explore more effective methods to relieve the pain of patients and improve their prognosis.CONCLUSION: At present,diffuse axonal injury has not attracted enough attentions in China,the mechanisms for its diagnosis and attack are still unclear,and the treatments are mainly aiming at the symptoms.

  17. Dopaminergic axon guidance: which makes what?

    Directory of Open Access Journals (Sweden)

    Laetitia ePrestoz

    2012-07-01

    Full Text Available Mesotelencephalic pathways in the adult central nervous system have been studied in great detail because of their implication in major physiological functions as well as in psychiatric, neurological and neurodegenerative diseases. However, the ontogeny of these pathways and the molecular mechanisms that guide dopaminergic axons during embryogenesis have been only recently studied. This line of research is of crucial interest for the repair of lesioned circuits in adulthood following neurodegenerative diseases or common traumatic injuries. For instance, in the adult, the anatomic and functional repair of the nigrostriatal pathway following dopaminergic embryonic neuron transplantation suggests that specific guidance cues exist which govern embryonic fibers outgrowth, and suggests that axons from transplanted embryonic cells are able to respond to theses cues, which then guide them to their final targets. In this review, we first synthesize the work that has been performed in the last few years on developing mesotelencephalic pathways, and summarize the current knowledge on the identity of cellular and molecular signals thought to be involved in establishing mesotelencephalic dopaminergic neuronal connectivity during embryogenesis in the central nervous system of rodents. Then, we review the modulation of expression of these molecular signals in the lesioned adult brain and discuss their potential role in remodeling the mesotelencephalic dopaminergic circuitry, with a particular focus on Parkinson’s disease. Identifying guidance molecules involved in the connection of grafted cells may be useful for cellular therapy in Parkinsonian patients, as these molecules may help direct axons from grafted cells along the long distance they have to travel from the substantia nigra to the striatum.

  18. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    DEFF Research Database (Denmark)

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

    2007-01-01

    at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein......Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...

  19. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis

    NARCIS (Netherlands)

    Cambron, Melissa; D'haeseleer, Miguel; Laureys, Guy; Clinckers, Ralph; Debruyne, Jan; De Keyser, Jacques

    2012-01-01

    In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in M

  20. Why Are Sensory Axons More Vulnerable for Ischemia than Motor Axons?

    NARCIS (Netherlands)

    Hofmeijer, Jeannette; Franssen, H.; van Schelven, L.J.; van Putten, Michel Johannes Antonius Maria

    2013-01-01

    Objective:In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.Methods:We measured median nerve compound sensory action potentials (CSAPs), compound muscle action

  1. IMP2 axonal localization, RNA interactome, and function in the development of axon trajectories

    DEFF Research Database (Denmark)

    Preitner, Nicolas; Quan, Jie; Li, Xinmin

    2016-01-01

    RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurological disease. Developing axons provide a model well suited to the study of RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles i...

  2. An unusual double supernumerary maxillary mesiodens in a Middle Iron Age skeleton from South Uist, Western Isles, Scotland.

    Science.gov (United States)

    Ives, Rachel

    2014-06-01

    Bilaterally occurring and fully erupted mesiodens occur infrequently in the modern population and have been little documented from past populations. This research presents an unusual case of a double maxillary mesiodens in the permanent dentition occurring in skeletal remains dating to the Middle Iron Age (250-410 AD) from South Uist, Western Isles of Scotland. Osteological analysis of an adult male included the inventory of teeth present/absent and analysis of dental pathologies (caries, calculus, periodontal disease, ante-mortem tooth loss, periapical abscesses), developmental defects and orthodontic anomalies (enamel hypoplastic defects, malposition, rotation, crowding, agenesis and supernumerary teeth). An unusual expression of double, fully erupted, mesiodens in the anterior permanent maxillary dentition representing supernumerary central incisors exists. The complete eruption had contributed to anterior displacement of one central incisor alveolar socket similar to documented modern clinical cases. Shallow sockets also implied an associated stunted development of the original central maxillary incisor roots. Occlusal enamel wear indicated the mesiodens had been abraded during mastication. Current clinical data suggest there is a much higher tendency for single mesiodens to exist rather than double and examples often fail to fully erupt into the dentition. This relative rarity may account for the few previous reports of this dental anomaly from past human remains and especially of this date. The fully erupted double example from South Uist contributes to the known evidence for orthodontic anomalies in the past. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. AxonPacking: An Open-Source Software to Simulate Arrangements of Axons in White Matter

    Science.gov (United States)

    Mingasson, Tom; Duval, Tanguy; Stikov, Nikola; Cohen-Adad, Julien

    2017-01-01

    HIGHLIGHTS AxonPacking: Open-source software for simulating white matter microstructure.Validation on a theoretical disk packing problem.Reproducible and stable for various densities and diameter distributions.Can be used to study interplay between myelin/fiber density and restricted fraction. Quantitative Magnetic Resonance Imaging (MRI) can provide parameters that describe white matter microstructure, such as the fiber volume fraction (FVF), the myelin volume fraction (MVF) or the axon volume fraction (AVF) via the fraction of restricted water (fr). While already being used for clinical application, the complex interplay between these parameters requires thorough validation via simulations. These simulations required a realistic, controlled and adaptable model of the white matter axons with the surrounding myelin sheath. While there already exist useful algorithms to perform this task, none of them combine optimisation of axon packing, presence of myelin sheath and availability as free and open source software. Here, we introduce a novel disk packing algorithm that addresses these issues. The performance of the algorithm is tested in term of reproducibility over 50 runs, resulting density, and stability over iterations. This tool was then used to derive multiple values of FVF and to study the impact of this parameter on fr and MVF in light of the known microstructure based on histology sample. The standard deviation of the axon density over runs was lower than 10−3 and the expected hexagonal packing for monodisperse disks was obtained with a density close to the optimal density (obtained: 0.892, theoretical: 0.907). Using an FVF ranging within [0.58, 0.82] and a mean inter-axon gap ranging within [0.1, 1.1] μm, MVF ranged within [0.32, 0.44] and fr ranged within [0.39, 0.71], which is consistent with the histology. The proposed algorithm is implemented in the open-source software AxonPacking (https://github.com/neuropoly/axonpacking) and can be useful for

  4. AxonPacking: An Open-Source Software to Simulate Arrangements of Axons in White Matter.

    Science.gov (United States)

    Mingasson, Tom; Duval, Tanguy; Stikov, Nikola; Cohen-Adad, Julien

    2017-01-01

    HIGHLIGHTS AxonPacking: Open-source software for simulating white matter microstructure.Validation on a theoretical disk packing problem.Reproducible and stable for various densities and diameter distributions.Can be used to study interplay between myelin/fiber density and restricted fraction. Quantitative Magnetic Resonance Imaging (MRI) can provide parameters that describe white matter microstructure, such as the fiber volume fraction (FVF), the myelin volume fraction (MVF) or the axon volume fraction (AVF) via the fraction of restricted water (fr). While already being used for clinical application, the complex interplay between these parameters requires thorough validation via simulations. These simulations required a realistic, controlled and adaptable model of the white matter axons with the surrounding myelin sheath. While there already exist useful algorithms to perform this task, none of them combine optimisation of axon packing, presence of myelin sheath and availability as free and open source software. Here, we introduce a novel disk packing algorithm that addresses these issues. The performance of the algorithm is tested in term of reproducibility over 50 runs, resulting density, and stability over iterations. This tool was then used to derive multiple values of FVF and to study the impact of this parameter on fr and MVF in light of the known microstructure based on histology sample. The standard deviation of the axon density over runs was lower than 10(-3) and the expected hexagonal packing for monodisperse disks was obtained with a density close to the optimal density (obtained: 0.892, theoretical: 0.907). Using an FVF ranging within [0.58, 0.82] and a mean inter-axon gap ranging within [0.1, 1.1] μm, MVF ranged within [0.32, 0.44] and fr ranged within [0.39, 0.71], which is consistent with the histology. The proposed algorithm is implemented in the open-source software AxonPacking (https://github.com/neuropoly/axonpacking) and can be useful for

  5. Differential extraction of axonally transported proteoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Elam, J.S. (Florida State Univ., Tallahassee (USA))

    1990-10-01

    Axonally transported proteoglycans were differentially solubilized by a sequence of extractions designed to infer their relationship to nerve terminal membranes. Groups of goldfish were injected unilaterally with 35SO4 and contralateral optic tecta containing axonally transported molecules were removed 16 h later. Tecta were homogenized in isotonic buffer and centrifuged at 100,000 g for 60 min to create a total supernatant fraction. Subsequent homogenizations followed by recentrifugation were with hypotonic buffer (lysis extract), 1 M NaCl, Triton X-100 or alternatively Triton-1 M NaCl. Populations of proteoglycans in each extract were isolated on DEAE ion exchange columns and evaluated for content of glycosaminoglycans (GAGs). Results show the distribution of transported proteoglycans to be 26.3% total soluble, 13.7% lysis extract, 13.8% NaCl extract, 12.2% Triton extract, and 46.2% Triton-NaCl extract. Proteoglycans from all fractions contained heparan sulfate as the predominant GAG, with lesser amounts of chondroitin (4 or 6) sulfate. The possible localizations of transported proteoglycans suggested by the extraction results are discussed.

  6. Dosage Effects of X and Y Chromosomes on Language and Social Functioning in Children with Supernumerary Sex Chromosome Aneuploidies: Implications for Idiopathic Language Impairment and Autism Spectrum Disorders

    Science.gov (United States)

    Lee, Nancy Raitano; Wallace, Gregory L.; Adeyemi, Elizabeth I.; Lopez, Katherine C.; Blumenthal, Jonathan D.; Clasen, Liv S.; Giedd, Jay N.

    2012-01-01

    Background: Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and…

  7. Molecular Determinants Fundamental to Axon Regeneration after SCI

    Science.gov (United States)

    2014-09-01

    TITLE: Molecular Determinants Fundamental to Axon Regeneration after SCI PRINCIPAL INVESTIGATOR: Jeffrey Alan Plunkett, Ph.D. Martin...TYPE FINAL 3. DATES COVERED (From - To) 1 Sept 2011 - 1 Sept 2014 4. TITLE AND SUBTITLE Molecular Determinants Fundamental to Axon Regeneration...available that restore motor impairments resulting fromspinal cord injury (SCI). Soldiers with SCI are permanently paralyzed and in needof lifelong care

  8. Inhibiting poly(ADP-ribosylation) improves axon regeneration

    Science.gov (United States)

    Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc

    2016-01-01

    The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration. DOI: http://dx.doi.org/10.7554/eLife.12734.001

  9. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    DEFF Research Database (Denmark)

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard

    2002-01-01

    Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total l...

  10. Neuronal Logistics : Axonal Transport in Development and Disease

    NARCIS (Netherlands)

    R. van den Berg (Robert)

    2016-01-01

    markdownabstractBrain cells are uniquely shaped among the many cell types of the body. While most cells are more or less rounded or square-shaped, neurons grow one or more long axons that can reach lengths of a meter or more. To keep these axons alive and functional, neurons are dependent on an intr

  11. Axon guidance of rat cortical neurons by microcontact printed gradients.

    Science.gov (United States)

    Fricke, Rita; Zentis, Peter D; Rajappa, Lionel T; Hofmann, Boris; Banzet, Marko; Offenhäusser, Andreas; Meffert, Simone H

    2011-03-01

    Substrate-bound gradients expressed in numerous spatio-temporal patterns play a crucial role during the development of complex neural circuits. A deeper understanding of the axon guidance mechanism is provided by studying the effect of a defined substrate-bound cue on a confined neural network. In this study, we constructed a discontinuous substrate-bound gradient to control neuronal cell position, the path of neurite growth, and axon directionality. A variety of gradient patterns, with slight changes in slope, width, and length were designed and fabricated by microcontact printing using laminin/poly-l-lysine (PLL) or PLL alone. The gradients were tested for neurite growth and their impact on axon guidance of embryonic rat cortical neurons. The neurite length was determined and the axon was evaluated by Tau-1 immunostaining. We found that the microgradients of laminin/PLL and PLL directed neurons' adhesion, differentially controlled the neurite growth, and guided up to 84% of the axons. The effect of the protein micropattern on axon guidance and neurite growth depended on the protein and geometric parameters used. Our approach proved to be very successful in guiding axons of single multipolar neurons with very high efficiency. It could thereby be useful to engineer defined neural networks for analyzing signal processing of functional circuits, as well as to unravel fundamental questions of the axon guidance mechanism.

  12. Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss of APP in Mouse Models

    OpenAIRE

    Smith, Karen D.B.; Erica Peethumnongsin; Han Lin; Hui Zheng; Pautler, Robia G.

    2010-01-01

    Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport ...

  13. SnoN facilitates axonal regeneration after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Jiun L Do

    Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

  14. Signaling mechanisms in cortical axon growth, guidance and branching

    Directory of Open Access Journals (Sweden)

    Katherine eKalil

    2011-09-01

    Full Text Available Precise wiring of cortical circuits during development depends upon axon extension, guidance and branching to appropriate targets. Motile growth cones at axon tips navigate through the nervous system by responding to molecular cues, which modulate signaling pathways within axonal growth cones. Intracellular calcium signaling has emerged as a major transducer of guidance cues but exactly how calcium signaling pathways modify the actin and microtubule cytoskeleton to evoke growth cone behaviors and axon branching is still mysterious. Axons must often pause in their outgrowth while their branches extend into targets. Some evidence suggests a competition between growth of axons and branches but the mechanisms are poorly understood. Since it is difficult to study growing axons deep within the mammalian brain, much of what we know about signaling pathways and cytoskeletal dynamics has come from studies of axonal growth cones, in many cases from non-mammalian species, growing in tissue culture. Consequently it is not well understood how guidance cues relevant to mammalian neural development in vivo signal to the growth cone cytoskeleton during axon outgrowth and guidance. In this review we describe our recent work in dissociated cultures of developing rodent sensorimotor cortex in the context of the current literature on molecular guidance cues, calcium signaling pathways and cytoskeletal dynamics that regulate growth cone behaviors. A major challenge is to relate findings in tissue culture to mechanisms of cortical development in vivo. Toward this goal, we describe our recent work in cortical slices, which preserve the complex cellular and molecular environment of the mammalian brain but allow direct visualization of growth cone behaviors and calcium signaling. Findings from this work suggest that mechanisms regulating axon growth and guidance in dissociated culture neurons also underlie development of cortical connectivity in vivo.

  15. Plasticity of the Axon Initial Segment

    DEFF Research Database (Denmark)

    Petersen, Anders Victor; Cotel, Florence; Perrier, Jean François

    2017-01-01

    of metabotropic receptors modulates the properties of ion channels expressed at the AIS within seconds and consequently produces fast adjustments of neuronal excitability. Recent results suggest that this plasticity plays important roles in physiological functions as diverse as memory formation, hearing......The axon initial segment (AIS) is a key neuronal compartment because it is responsible for action potential initiation. The local density of Na+ channels, the biophysical properties of K+ channels, as well as the length and diameter of the AIS determine the spiking of neurons. These parameters...... undergo important modifications during development. The development of the AIS is governed by intrinsic mechanisms. In addition, surrounding neuronal networks modify its maturation. As a result, neurons get tuned to particular physiological functions. Neuronal activity also influences the morphology...

  16. Clinical features of diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyze the mechanism of diffuse axonal injury (DAI) and study the relationship between DAI and brain concussion, brain contusion, and primary brain stem injury.Methods: The clinical data and iconographic characteristics of 56 patients with DAI were analyzed retrospectively.Results: Traffic accidents were the main cause of DAI. Among the 56 cases, 34 were injured for at least twice, and 71.43% of the patients were complicated with contusion.Conclusions: It is considered that DAI is a common pattern of primary brain injury, which is often underestimated. And DAI includes cerebral concussion and primary brain injury, and is often complicated by cerebral cortex contusion. Therefore, it is very simple and practical to divide primary brain injuries into local and diffuse injuries.

  17. Cobalt inhibits motility of axonal mitochondria and induces axonal degeneration in cultured dorsal root ganglion cells of rat.

    Science.gov (United States)

    Kikuchi, Shin; Ninomiya, Takafumi; Kohno, Takayuki; Kojima, Takashi; Tatsumi, Haruyuki

    2017-06-27

    Cobalt is a trace element that localizes in the human body as cobalamin, also known as vitamin B12. Excessive cobalt exposure induces a peripheral neuropathy, the mechanisms of which are yet to be elucidated. We investigated how cobalt may affect mitochondrial motility in primary cultures of rat dorsal root ganglion (DRG). We observed mitochondrial motility by time-lapse imaging after DsRed2 tagging via lentivirus, mitochondrial structure using transmission electron microscopy (TEM), and axonal swelling using immunocytochemical staining. The concentration of cobaltous ion (Co(2+)) required to significantly suppress mitochondrial motility is lower than that required to induce axonal swelling following a 24-h treatment. Exposure to relatively low concentrations of Co(2+) for 48 h suppressed mitochondrial motility without leading to axonal swelling. TEM images indicated that Co(2+) induces mitochondrial destruction. Our results show that destruction of the axonal mitochondria precedes the axonal degeneration induced by Co(2+) exposure.

  18. Impacted lower third molar fused with a supernumerary tooth--diagnosis and treatment planning using cone-beam computed tomography.

    Science.gov (United States)

    Ferreira-Junior, Osny; de Avila, Luciana Dorigatti; Sampieri, Marcelo Bonifácio da Silva; Dias-Ribeiro, Eduardo; Chen, Wei-liang; Fan, Song

    2009-12-01

    This paper reported a case of fusion between an impacted third molar and a supernumerary tooth, in which a surgical intervention was carried out, with the objective of removing the dental elements. The panoramic radiography was complemented by the Donovan's radiographic technique; but because of the proximity of the dental element to the mandibular ramus, it was not possible to have a final fusion diagnosis. Hence, the Cone-Beam Computed Tomography-which provides precise three-dimensional information-was used to determinate the fusion diagnosis and also to help in the surgical planning. In this case report we observed that the periapical, occlusal and panoramic were not able to show details which could only be examined through the cone-beam computed tomography.

  19. Pure and complete trisomy 18p due to a supernumerary marker chromosome associated with moderate mental retardation.

    Science.gov (United States)

    Mabboux, P; Brisset, S; Aboura, A; Pineau, D; Koubi, V; Joannidis, S; Labrune, P; Tachdjian, G

    2007-04-01

    Trisomy for the short arm of chromosome 18 or trisomy 18p, is rarely described. We report on a 13-year-old boy with minor facial anomalies, mental retardation, bilateral cryptorchidism associated with a de novo supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization and comparative genomic hybridization analyses, this SMC corresponded to the p arm of chromosome 18 associated with a centromere of either chromosome 13 or 21 and nucleolus organizing regions (NORs). We report here the first case of a pure and complete trisomy 18p due to a SMC. This report and review of literature confirm that the main phenotypic anomaly associated with trisomy 18p is moderate mental retardation.

  20. Revascularization of an impacted, immature dilacerated permanent maxillary central incisor associated with odontoma and a supernumerary tooth

    Directory of Open Access Journals (Sweden)

    Priya Subramaniam

    2013-01-01

    Full Text Available To intentionally replant an impacted immature permanent maxillary central incisor in the mixed dentition period followed by revascularization in order to achieve apical root closure. A 9-year-old boy presented with retained maxillary left primary incisors. Radiographic evaluation revealed the presence of a supernumerary tooth and an odontoma associated with an impacted permanent maxillary left central incisor, having root dilaceration. Treatment included surgical removal of mesiodens and odontoma. The impacted dilacerated permanent central incisor was removed and intentionally replanted, followed by revascularization of pulp. During the follow-up, root end closure with narrowing of canal space was observed, patient has been asymptomatic and the tooth remains vital. Revascularization of the immature reimplanted tooth showed continued root development and thickening of the lateral dentinal walls through deposition of new hard tissue and narrowing of the canal space.

  1. Characterization of a prenatally assessed de novo supernumerary minute ring chromosome 20 in a phenotypically normal male

    Directory of Open Access Journals (Sweden)

    Garas Antonios

    2009-01-01

    Full Text Available Abstract Background The heterogeneous group of small supernumerary marker chromosomes (sSMCs presents serious counseling problems, especially if they are present de novo and diagnosed prenatally. The incidence has been estimated at 1 in 1000 prenatal samples. We present a case of mosaic sSMC diagnosed prenatally after amniocentesis. The sSMC was characterized by various molecular cytogenetic techniques and determined to be a r(20 chromosome. After genetic counseling, the parents decided to continue the pregnancy, and a boy with minor phenotypic variants was born after 39 weeks of pregnancy. The case is compared with four other cases of prenatally detected r(20 mosaicism. Results Here we describe a 3 months old male child with normal pre- and postnatal development and with a de novo ring supernumerary marker chromosome in amniocytes cultures. Using new fluorescence in situ hybridization (FISH techniques, three distinguishable sSMCs (cryptic mosaicism, all derived from chromosome 20, were observed, including ring and minute chromosomes. This heterogeneity was impossible to detect by the conventional G-banding technique or conventional FISH technique that were used before the application of new FISH techniques (subcentromere-specific multicolor-FISH [subcenM-FISH] and a probe, specific for the 20p12.2 band. The sSMC present in 25% of the cells was present as r(20(::p12.2~12.3->q11.1::5/r(20;20(::p12.1->q11.1::q11.1 >p12.1::2/min(20;20(:p12.1->q11.1::q11.1->p12.1:1. The final karyotype was 47,XY,+r(20[25%]/46,XY[75%]. Conclusion We emphasize the importance of application of molecular cytogenetics in a prenatally diagnostic laboratory and description of more cases to enable a better genetic counseling and risk evaluation.

  2. Local erythropoietin signaling enhances regeneration in peripheral axons.

    Science.gov (United States)

    Toth, C; Martinez, J A; Liu, W Q; Diggle, J; Guo, G F; Ramji, N; Mi, R; Hoke, A; Zochodne, D W

    2008-06-23

    Erythropoietin (EPO) and its receptor (EPO-R), mediate neuroprotection from axonopathy and apoptosis in the peripheral nervous system (PNS). We examined the impact and potential mechanisms of local EPO signaling on regenerating PNS axons in vivo and in vitro. As a consequence of injury, peripheral nerve axons and DRG neurons have a marked increase in the expression of EPO and EPO-R. Local delivery of EPO via conduit over 2 weeks to rat sciatic nerve following crush injury increased the density and maturity of regenerating myelinated axons growing distally from the crush site. In addition, EPO also rescued retrograde degeneration and atrophy of axons. EPO substantially increased the density and intensity of calcitonin gene-related peptide (CGRP) expression within outgrowing axons. Behavioral improvements in sensorimotor function also occurred in rats exposed to near nerve EPO delivery. EPO delivery led to decreased nuclear factor kappaB (NFkB) activation but increased phosphorylation of Akt and STAT3 within nerve and dorsal root ganglia neurons indicating rescue from an injury phenotype. Spinal cord explant studies also demonstrated a similar dose-dependent effect of EPO upon motor axonal outgrowth. Local EPO signaling enhances regenerating peripheral nervous system axons in addition to its known neuroprotection. Exogenous EPO may have a therapeutic role in a large number of peripheral nerve diseases through its impact on regeneration.

  3. Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration.

    Science.gov (United States)

    Ma, Marek; Ferguson, Toby A; Schoch, Kathleen M; Li, Jian; Qian, Yaping; Shofer, Frances S; Saatman, Kathryn E; Neumar, Robert W

    2013-08-01

    In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca(2+)-dependent protease calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 h after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration.

  4. Ndel1 promotes axon regeneration via intermediate filaments.

    Directory of Open Access Journals (Sweden)

    Cory Toth

    Full Text Available Failure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF Vimentin while dissociating from the mature neuronal IF (Neurofilament light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration.

  5. Axon guidance and neuronal migration research in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by Chinese neuroscientists to investigate the molecular machinery underlying these guidance events.

  6. Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons.

    Science.gov (United States)

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A

    2010-05-19

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.

  7. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  8. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Science.gov (United States)

    Huettl, Rosa-Eva; Soellner, Heidi; Bianchi, Elisa; Novitch, Bennett G; Huber, Andrea B

    2011-02-01

    The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  9. Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

    Directory of Open Access Journals (Sweden)

    Andrew D. Nelson

    2017-05-01

    Full Text Available Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of

  10. Noninvasive Detection and Differentiation of Axonal Injury/Loss, Demyelination, and Inflammation

    Science.gov (United States)

    2015-10-01

    spectrum imaging, diffusion tensor imaging, EAE, inflammation, axonal injury, curizone, demyelination, optic neuritis, axonal loss 16. SECURITY...Multiple sclerosis, diffusion basis spectrum imaging, diffusion tensor imaging, EAE, inflammation, axonal injury, demyelination, axonal loss, optic...biomarkers have recently been evaluated in MS [12-14]. Diffusion tensor imaging (DTI), in particular, is one of the commonest tools for evaluating white

  11. Axon diameter mapping in crossing fibers with diffusion MRI

    DEFF Research Database (Denmark)

    Zhang, Hui; Dyrby, Tim B; Alexander, Daniel C

    2011-01-01

    tissue than measures derived from diffusion tensor imaging. Most existing techniques for axon diameter mapping assume a single axon orientation in the tissue model, which limits their application to only the most coherently oriented brain white matter, such as the corpus callosum, where the single...... orientation assumption is a reasonable one. However, fiber crossings and other complex configurations are widespread in the brain. In such areas, the existing techniques will fail to provide useful axon diameter indices for any of the individual fiber populations. We propose a novel crossing fiber tissue...... of the technique by establishing reasonable axon diameter indices in the crossing region at the interface of the cingulum and the corpus callosum....

  12. Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy.

    Science.gov (United States)

    Persson, Anna-Karin; Hoeijmakers, Janneke G J; Estacion, Mark; Black, Joel A; Waxman, Stephen G

    2016-05-01

    Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition.

  13. Structural plasticity of axon terminals in the adult.

    Science.gov (United States)

    Gogolla, Nadine; Galimberti, Ivan; Caroni, Pico

    2007-10-01

    There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity complements that of postsynaptic spines, but axonal plasticity samples larger volumes of neuropil, and has a larger impact on circuit remodeling. Axons from distinct neurons exhibit unique ratios of stable (t1/2>9 months) and dynamic (t1/2 5-20 days) boutons, which persist as spatially intermingled subgroups along terminal arbors. In addition, phases of side-branch dynamics mediate larger scale remodeling guided by synaptogenesis. The plasticity is most pronounced during critical periods; its patterns and outcome are controlled by Hebbian mechanisms and intrinsic neuronal factors. Novel experience, skill learning, life-style, and age can persistently modify local circuit structure through axonal structural plasticity.

  14. Modality-Specific Axonal Regeneration: Towards selective regenerative neural interfaces

    Directory of Open Access Journals (Sweden)

    Parisa eLotfi

    2011-10-01

    Full Text Available Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed submodality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type-specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF and neurotrophin-3 (NT-3, to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5 fold compared to that in saline or NT-3, whereas the number of branches increased 3 fold in the NT-3 channels. These results were confirmed using a 3-D Y-shaped in vitro assay showing that the arm containing NGF was able to entice a 5-fold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a Y-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted towards the sural nerve, while N-52+ large diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  15. Electrophysiology of a nonmyelinated glutamatergic axon in rat hippocampus

    OpenAIRE

    Alle, Henrik

    2012-01-01

    The common theme of the presented work on the nonmyelinated hippocampal mossy fiber (the axon of the granule cell in the dentate gyrus) is the generation of subthreshold and suprathreshold electrical signals. Subthreshold depolarizations in the axon can occur due to passive propagation of excitatory postsynaptic potentials, which are generated in the somato-dendritic domain. The remote passive propagation of these comparatively slow but transient signals is due to a space constant...

  16. Axonal noise as a source of synaptic variability.

    Directory of Open Access Journals (Sweden)

    Ali Neishabouri

    2014-05-01

    Full Text Available Post-synaptic potential (PSP variability is typically attributed to mechanisms inside synapses, yet recent advances in experimental methods and biophysical understanding have led us to reconsider the role of axons as highly reliable transmission channels. We show that in many thin axons of our brain, the action potential (AP waveform and thus the Ca++ signal controlling vesicle release at synapses will be significantly affected by the inherent variability of ion channel gating. We investigate how and to what extent fluctuations in the AP waveform explain observed PSP variability. Using both biophysical theory and stochastic simulations of central and peripheral nervous system axons from vertebrates and invertebrates, we show that channel noise in thin axons (<1 µm diameter causes random fluctuations in AP waveforms. AP height and width, both experimentally characterised parameters of post-synaptic response amplitude, vary e.g. by up to 20 mV and 0.5 ms while a single AP propagates in C-fibre axons. We show how AP height and width variabilities increase with a ¾ power-law as diameter decreases and translate these fluctuations into post-synaptic response variability using biophysical data and models of synaptic transmission. We find for example that for mammalian unmyelinated axons with 0.2 µm diameter (matching cerebellar parallel fibres axonal noise alone can explain half of the PSP variability in cerebellar synapses. We conclude that axonal variability may have considerable impact on synaptic response variability. Thus, in many experimental frameworks investigating synaptic transmission through paired-cell recordings or extracellular stimulation of presynaptic neurons, causes of variability may have been confounded. We thereby show how bottom-up aggregation of molecular noise sources contributes to our understanding of variability observed at higher levels of biological organisation.

  17. Morphology of axonal transport abnormalities in primate eyes.

    Science.gov (United States)

    Radius, R L; Anderson, D R

    1981-11-01

    The ultrastructure of the retina and optic nerve head was studied in primate eyes after central retinal artery occlusion. Within 2 hours of the vascular occlusion the inner retinal layers undergo watery (isosmotic) swelling. This watery swelling of axons and astroglia extends into the nerve head as far back as the anterior boundary of the scleral lamina cribrosa. The swelling is increased 4 hours after the occlusion, and by 24 hours disintegration has occurred. At the optic nerve head mitochondria and vesicles of smooth endoplasmic reticulum begin to accumulate within 2 hours. The accumulation increases at 4 hours and persists to 24 hours. The watery swelling seems characteristic of ischaemic axons. Membranous organelles accumulate at the boundary of an ischaemic zone when material carried by axonal transport is brought via the healthy axon segment to the boundary, but they cannot proceed further into the ischaemic zone. Such accumulation is typical of locations where rapid orthograde axonal transport or retrograde axonal transport is blocked. In contrast, when slow axonal flow is impaired, the swelling is characterised by an excess of cytoplasmic gel without a marked accumulation of organelles. Rapid orthograde transport and retrograde transport seem to be closely related to one another, while slow axoplasmic flow seems fundamentally different. From morphological findings we suspect that, in experimental glaucoma, intraocular pressure first affects the intracellular physiological process of rapid orthograde and retrograde axonal transport. Watery swelling may not occur unless the ischaemic injury to cell metabolism is more advanced. In contrast, in experimental papilloedema, the swelling results predominantly from impaired slow axoplasmic flow.

  18. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  19. Early Commissural Diencephalic Neurons Control Habenular Axon Extension and Targeting.

    Science.gov (United States)

    Beretta, Carlo A; Dross, Nicolas; Guglielmi, Luca; Bankhead, Peter; Soulika, Marina; Gutierrez-Triana, Jose A; Paolini, Alessio; Poggi, Lucia; Falk, Julien; Ryu, Soojin; Kapsimali, Marika; Engel, Ulrike; Carl, Matthias

    2017-01-23

    Most neuronal populations form on both the left and right sides of the brain. Their efferent axons appear to grow synchronously along similar pathways on each side, although the neurons or their environment often differ between the two hemispheres [1-4]. How this coordination is controlled has received little attention. Frequently, neurons establish interhemispheric connections, which can function to integrate information between brain hemispheres (e.g., [5]). Such commissures form very early, suggesting their potential developmental role in coordinating ipsilateral axon navigation during embryonic development [4]. To address the temporal-spatial control of bilateral axon growth, we applied long-term time-lapse imaging to visualize the formation of the conserved left-right asymmetric habenular neural circuit in the developing zebrafish embryo [6]. Although habenular neurons are born at different times across brain hemispheres [7], we found that elongation of habenular axons occurs synchronously. The initiation of axon extension is not controlled within the habenular network itself but through an early developing proximal diencephalic network. The commissural neurons of this network influence habenular axons both ipsilaterally and contralaterally. Their unilateral absence impairs commissure formation and coordinated habenular axon elongation and causes their subsequent arrest on both sides of the brain. Thus, habenular neural circuit formation depends on a second intersecting commissural network, which facilitates the exchange of information between hemispheres required for ipsilaterally projecting habenular axons. This mechanism of network formation may well apply to other circuits, and has only remained undiscovered due to technical limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 6-Sulphated chondroitins have a positive influence on axonal regeneration.

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    Rachel Lin

    Full Text Available Chondroitin sulphate proteoglycans (CSPGs upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs. Chondroitin 6-sulphotransferase-1 (C6ST-1 is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs. Using C6ST-1 knockout mice (KO, we studied post-injury changes in chondroitin sulphotransferase (CSST expression and the effect of chondroitin 6-sulphates on both central and peripheral axon regeneration. After CNS injury, wild-type animals (WT showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2. We examined regeneration of nigrostriatal axons, which demonstrate mild spontaneous axon regeneration in the WT. KO showed many fewer regenerating axons and more axonal retraction than WT. However, in the PNS, repair of the median and ulnar nerves led to similar and normal levels of axon regeneration in both WT and KO. Functional tests on plasticity after the repair also showed no evidence of enhanced plasticity in the KO. Our results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration, and that the balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury.

  1. Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

    Science.gov (United States)

    Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

    2015-01-01

    The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

  2. Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording

    DEFF Research Database (Denmark)

    Petersen, Anders V.; Johansen, Emil O.; Perrier, Jean-Francois

    2015-01-01

    The axon initial segment (AIS) is an essential neuronal compartment. It is usually where action potentials are initiated. Recent studies demonstrated that the AIS is a plastic structure that can be regulated by neuronal activity and by the activation of metabotropic receptors. Studying the AIS...... of neurons, we can detect sinks caused by inward currents flowing across the membrane. We determine the location of the AIS by comparing the timing of these events with the action potential. We demonstrate that this method allows the unequivocal identification of the AIS of different types of neurons from...

  3. Parametric Probability Distribution Functions for Axon Diameters of Corpus Callosum

    Directory of Open Access Journals (Sweden)

    Farshid eSepehrband

    2016-05-01

    Full Text Available Axon diameter is an important neuroanatomical characteristic of the nervous system that alters in the course of neurological disorders such as multiple sclerosis. Axon diameters vary, even within a fiber bundle, and are not normally distributed. An accurate distribution function is therefore beneficial, either to describe axon diameters that are obtained from a direct measurement technique (e.g., microscopy, or to infer them indirectly (e.g., using diffusion-weighted MRI. The gamma distribution is a common choice for this purpose (particularly for the inferential approach because it resembles the distribution profile of measured axon diameters which has been consistently shown to be non-negative and right-skewed. In this study we compared a wide range of parametric probability distribution functions against empirical data obtained from electron microscopy images. We observed that the gamma distribution fails to accurately describe the main characteristics of the axon diameter distribution, such as location and scale of the mode and the profile of distribution tails. We also found that the generalized extreme value distribution consistently fitted the measured distribution better than other distribution functions. This suggests that there may be distinct subpopulations of axons in the corpus callosum, each with their own distribution profiles. In addition, we observed that several other distributions outperformed the gamma distribution, yet had the same number of unknown parameters; these were the inverse Gaussian, log normal, log logistic and Birnbaum-Saunders distributions.

  4. Axon-glia interaction and membrane traffic in myelin formation.

    Science.gov (United States)

    White, Robin; Krämer-Albers, Eva-Maria

    2014-01-06

    In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasizing the central role of the Src-family kinase Fyn during central nervous system (CNS) myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of proteolipid protein (PLP) transport by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  5. Axon morphology at the lamina cribrosa in monkey eyes.

    Science.gov (United States)

    Radius, R L; Klewin, K M

    1986-01-01

    The eyes of 8 monkeys (Aotus trivirgatus) were studied. The mean cross-section area and the least diameter of axon cylinders were calculated from measurements made by computer assisted planimetry of electron photomicrographs of sections through the optic nerve head at the level of the lamina cribrosa. The density of intrabundle connective tissue and glial cell elements in nerve fiber bundles was also calculated. The mean cross-section area and minimum diameter of axons in the temporal part were less than in the nasal part of the nerve. The values for axons in the superior and inferior parts of the nerve were intermediate. A similar pattern of increasing dimensions was seen in axons from the more axial nerve compared to neurons in the more circumferential nerve sectors. The density of the intrabundle, nonaxonal tissue elements did not differ significantly across the nerve. Although axon dimensions may play some role in defining the vulnerability of neuronal tissue to a pressure insult, the results of this anatomic investigation do not support the hypothesis that differences in axonal distribution by size across the nerve section define the regional vulnerability of the nerve head to elevated intraocular pressure.

  6. Determinants of action potential propagation in cerebellar Purkinje cell axons.

    Science.gov (United States)

    Monsivais, Pablo; Clark, Beverley A; Roth, Arnd; Häusser, Michael

    2005-01-12

    Axons have traditionally been viewed as highly faithful transmitters of action potentials. Recently, however, experimental evidence has accumulated to support the idea that under some circumstances axonal propagation may fail. Cerebellar Purkinje neurons fire highfrequency simple spikes, as well as bursts of spikes in response to climbing fiber activation (the "complex spike"). Here we have visualized the axon of individual Purkinje cells to directly investigate the relationship between somatic spikes and axonal spikes using simultaneous somatic whole-cell and cell-attached axonal patch-clamp recordings at 200-800 microm from the soma. We demonstrate that sodium action potentials propagate at frequencies up to approximately 260 Hz, higher than simple spike rates normally observed in vivo. Complex spikes, however, did not propagate reliably, with usually only the first and last spikes in the complex spike waveform being propagated. On average, only 1.7 +/- 0.2 spikes in the complex spike were propagated during resting firing, with propagation limited to interspike intervals above approximately 4 msec. Hyperpolarization improved propagation efficacy without affecting total axonal spike number, whereas strong depolarization could abolish propagation of the complex spike. These findings indicate that the complex spike waveform is not faithfully transmitted to downstream synapses and that propagation of the climbing fiber response may be modulated by background activity.

  7. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (Pmotor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (Pdevelopment of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  8. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  9. Management of Developing Anterior Malocclusion due to SupernumeraryTooth with Preventive and Intercep-tive Approach: A 1½ Year Case Study

    Science.gov (United States)

    Kambalimath, HV; Banda, Naveen Reddy

    2010-01-01

    ABSTRACT Variety of clinical complications occurs due to the presence of supernumerary teeth, especially mesiodens. It may result in impaction of one or both central incisors which in turn may lead to a variety of malocclusions. Timely intervention not only prevents malocclusion but also the time taken for corrective orthodontics. A complete case report of developing mesiodens’ tooth germ resulting in malocclusion including treatment in 1½ year period is presented. PMID:27507922

  10. Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    孙晓川; 唐文渊; 郑履平

    2002-01-01

    Objective: To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury. Methods: Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n=6) in which the animal's core temperature was maintained at 36.0-37.5℃ and the hypothermia group (n=6) in which the core temperature was reduced to 32.0-32.5℃ after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n=3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system. Results: At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P<0.001), and a significant increase in the mean intermicrotubule spacing (P<0.05 or P<0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P<0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P<0.01) and an increase in the mean intermicrotubule spacing (P<0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P<0.05) and reduction in the mean interneurofilament spacing (P<0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not

  11. White matter involvement after TBI: Clues to axon and myelin repair capacity.

    Science.gov (United States)

    Armstrong, Regina C; Mierzwa, Amanda J; Marion, Christina M; Sullivan, Genevieve M

    2016-01-01

    Impact-acceleration forces to the head cause traumatic brain injury (TBI) with damage in white matter tracts comprised of long axons traversing the brain. White matter injury after TBI involves both traumatic axonal injury (TAI) and myelin pathology that evolves throughout the post-injury time course. The axon response to initial mechanical forces and secondary insults follows the process of Wallerian degeneration, which initiates as a potentially reversible phase of intra-axonal damage and proceeds to an irreversible phase of axon fragmentation. Distal to sites of axon disconnection, myelin sheaths remain for prolonged periods, which may activate neuroinflammation and inhibit axon regeneration. In addition to TAI, TBI can cause demyelination of intact axons. These evolving features of axon and myelin pathology also represent opportunities for repair. In experimental TBI, demyelinated axons exhibit remyelination, which can serve to both protect axons and facilitate recovery of function. Myelin remodeling may also contribute to neuroplasticity. Efficient clearance of myelin debris is a potential target to attenuate the progression of chronic pathology. During the early phase of Wallerian degeneration, interventions that prevent the transition from reversible damage to axon disconnection warrant the highest priority, based on the poor regenerative capacity of axons in the CNS. Clinical evaluation of TBI will need to address the challenge of accurately detecting the extent and stage of axon damage. Distinguishing the complex white matter changes associated with axons and myelin is necessary for interpreting advanced neuroimaging approaches and for identifying a broader range of therapeutic opportunities to improve outcome after TBI.

  12. Atomic Force Microscopy Reveals Important Differences in Axonal Resistance to Injury

    Science.gov (United States)

    Magdesian, Margaret H.; Sanchez, Fernando S.; Lopez, Monserratt; Thostrup, Peter; Durisic, Nela; Belkaid, Wiam; Liazoghli, Dalinda; Grütter, Peter; Colman, David R.

    2012-01-01

    Axonal degeneration after traumatic brain injury and nerve compression is considered a common underlying cause of temporary as well as permanent disability. Because a proper functioning of neural network requires phase coherence of all components, even subtle changes in circuitry may lead to network failure. However, it is still not possible to determine which axons will recover or degenerate after injury. Several groups have studied the pressure threshold for axonal injury within a nerve, but difficulty accessing the injured region; insufficient imaging methods and the extremely small dimensions involved have prevented the evaluation of the response of individual axons to injury. We combined microfluidics with atomic force microscopy and in vivo imaging to estimate the threshold force required to 1), uncouple axonal transport without impairing axonal survival, and 2), compromise axonal survival in both individual and bundled axons. We found that rat hippocampal axons completely recover axonal transport with no detectable axonal loss when compressed with pressures up to 65 ± 30 Pa for 10 min, while dorsal root ganglia axons can resist to pressures up to 540 ± 220 Pa. We investigated the reasons for the differential susceptibility of hippocampal and DRG axons to mechanical injury and estimated the elasticity of live axons. We found that dorsal root ganglia axons have a 20% lower elastic modulus than hippocampal axons. Our results emphasize the importance of the integrity of the axonal cytoskeleton in deciding the axonal fate after damage and open up new avenues to improve injury diagnosis and to identify ways to protect axons. PMID:22947856

  13. Axonal synapses utilize multiple synaptic ribbons in the mammalian retina.

    Directory of Open Access Journals (Sweden)

    Hong-Lim Kim

    Full Text Available In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

  14. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    Science.gov (United States)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  15. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    Science.gov (United States)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  16. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system.

    Science.gov (United States)

    Lopez-Verrilli, María Alejandra; Picou, Frederic; Court, Felipe A

    2013-11-01

    Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor-like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal regeneration. Here we show that dedifferentiated SCs secrete nano-vesicles known as exosomes which are specifically internalized by axons. Surprisingly, SC-derived exosomes markedly increase axonal regeneration in vitro and enhance regeneration after sciatic nerve injury in vivo. Exosomes shift the growth cone morphology to a pro-regenerating phenotype and decrease the activity of the GTPase RhoA, involved in growth cone collapse and axon retraction. Altogether, our work identifies a novel mechanism by which SCs communicate with neighboring axons during regenerative processes. We propose that SC exosomes represent an important mechanism by which these cells locally support axonal maintenance and regeneration after nerve damage.

  17. The voltage dependence of Ih in human myelinated axons

    Science.gov (United States)

    Howells, James; Trevillion, Louise; Bostock, Hugh; Burke, David

    2012-01-01

    HCN channels are responsible for Ih, a voltage-gated inwardly rectifying current activated by hyperpolarization. This current appears to be more active in human sensory axons than motor and may play a role in the determination of threshold. Differences in Ih are likely to be responsible for the high variability in accommodation to hyperpolarization seen in different subjects. The aim of this study was to characterise this current in human axons, both motor and sensory. Recordings of multiple axonal excitability properties were performed in 10 subjects, with a focus on the changes in threshold evoked by longer and stronger hyperpolarizing currents than normally studied. The findings confirm that accommodation to hyperpolarization is greater in sensory than motor axons in all subjects, but the variability between subjects was greater than the modality difference. An existing model of motor axons was modified to take into account the behaviour seen with longer and stronger hyperpolarization, and a mathematical model of human sensory axons was developed based on the data collected. The differences in behaviour of sensory and motor axons and the differences between different subjects are best explained by modulation of the voltage dependence, along with a modest increase of expression of the underlying conductance of Ih. Accommodation to hyperpolarization for the mean sensory data is fitted well with a value of −94.2 mV for the mid-point of activation (V0.5) of Ih as compared to −107.3 mV for the mean motor data. The variation in response to hyperpolarization between subjects is accounted for by varying this parameter for each modality (sensory: −89.2 to −104.2 mV; motor −87.3 to −127.3 mV). These voltage differences are within the range that has been described for physiological modulation of Ih function. The presence of slowly activated Ih isoforms on both motor and sensory axons was suggested by modelling a large internodal leak current and a masking of

  18. In search for significant cognitive features in Klinefelter syndrome through cross-species comparison of a supernumerary X chromosome.

    Science.gov (United States)

    Bruining, H; Swaab, H; de Sonneville, L M J; van Rijn, S; van Engeland, H; Kas, M J H

    2011-08-01

    The behavioral characterization of animals that carry genetic disorder abnormalities in a controlled genetic and environmental background may be used to identify human deficits that are significant to understand underlying neurobiological mechanisms. Here, we studied whether previously reported object recognition impairments in mice with a supernumerary X chromosome relate to specific cognitive deficits in Klinefelter syndrome (47,XXY). We aimed to optimize face validity by studying temporal object recognition in human cognitive assays. Thirty-four boys with Klinefelter syndrome (mean age 12.01) were compared with 90 age-matched normal controls, on a broad range of visual object memory tasks, including tests for pattern and temporal order discrimination. The results indicate that subjects with Klinefelter syndrome have difficulty in the processing of visual object and pattern information. Visual object patterns seem difficult to discriminate especially when temporal information needs to be processed and reproduced. On the basis of cross-species comparison, we propose that impaired temporal processing of object pattern information is an important deficit in Klinefelter syndrome. The current study shows how cross-species behavioral characterization may be used as a starting point to understand the neurobiology of syndromal phenotypic expression. The features of this study may serve as markers for interventions in Klinefelter syndrome. Similar cross-species evaluations of standard mouse behavioral paradigms in different genetic contexts may be powerful tools to optimize genotype-phenotype relationships.

  19. Unusually rapid growth of brown tumour in the mandible after parathyroidectomy associated with the presence of a supernumerary parathyroid gland.

    Science.gov (United States)

    Dorigatti de Ávila, Érica; de Molon, Rafael Scaf; Cabrini Gabrielli, Marisa Aparecida; Hochuli-Vieira, Eduardo; Sgavioli Massucato, Elaine Maria; de Mello-Filho, Francisco Veríssimo; Conti, Luis Carlos; Real Gabrielli, Mário Francisco

    2012-01-01

    The aim of this study is to report the case of a quick growing brown tumour in the jaw after a parathyroidectomy due to the presence of a rare fifth parathyroid gland. The patient had chronic renal disease and the diagnosis was tertiary hyperparathyroidism. Thirty days after the parathyroidectomy, the patient returned with a significant increase in the tumour size. The suspicion of a supernumerary gland was confirmed by parathyroid scintigraphy. The treatment of brown tumour is dependent on the treatment of the hyperparathyroidism. However, curettage should be considered if a large lesion is disturbing mastication. In conclusion, this case should attract the attention of general practitioner dentists, since they may be the first professionals who have contact with the patient with a brown tumour in the jaws. Likewise, this case emphasises the importance of knowing the type of hyperparathyroidism involved to allow for effective treatment planning. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  20. Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1 regulate supernumerary organ formations.

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    Honoka Kiso

    Full Text Available Bone morphogenetic proteins (BMPs are highly conserved signaling molecules that are part of the transforming growth factor (TGF-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1 suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

  1. B chromosome dynamics in Prochilodus costatus (Teleostei, Characiformes) and comparisons with supernumerary chromosome system in other Prochilodus species

    Science.gov (United States)

    Melo, Silvana; Utsunomia, Ricardo; Penitente, Manolo; Sobrinho-Scudeler, Patrícia Elda; Porto-Foresti, Fábio; Oliveira, Claudio; Foresti, Fausto; Dergam, Jorge Abdala

    2017-01-01

    Abstract Within the genus Prochilodus Agassiz, 1829, five species are known to carry B chromosomes, i.e. chromosomes beyond the usual diploid number that have been traditionally considered as accessory for the genome. Chromosome microdissection and mapping of repetitive DNA sequences are effective tools to assess the DNA content and allow a better understanding about the origin and composition of these elements in an array of species. In this study, a novel characterization of B chromosomes in Prochilodus costatus Valenciennes, 1850 (2n=54) was reported for the first time and their sequence complementarity with the supernumerary chromosomes observed in Prochilodus lineatus (Valenciennes, 1836) and Prochilodus argenteus Agassiz, 1829 was investigated. The hybridization patterns obtained with chromosome painting using the micro B probe of P. costatus and the satDNA SATH1 mapping made it possible to assume homology of sequences between the B chromosomes of these congeneric species. Our results suggest that the origin of B chromosomes in the genus Prochilodus is a phylogenetically old event. PMID:28919971

  2. Small supernumerary marker chromosomes derived from chromosomes 6 and 20 in a woman with recurrent spontaneous abortions.

    Science.gov (United States)

    Guediche, Narjes; Tosca, Lucie; Nouchy, Marc; Lecerf, Laure; Cornet, Dominique; Brisset, Sophie; Goossens, Michel; Tachdjian, Gérard

    2012-12-01

    In this report, we describe a case of multiple small supernumerary marker chromosomes (sSMC) presenting with recurrent abortions. Peripheral blood lymphocytes of a young, healthy and non-consanguineous couple who asked for genetic evaluation after two spontaneous miscarriages were obtained for karyotypes. Lymphocytes of the woman were analyzed by FISH techniques and DNA was extracted and used for array CGH investigation. Karyotyping revealed 48,XX,+2mar[24]/47,XX,+mar[5]/46,XX[3] for the woman and 46,XY for her husband. FISH analysis showed that the two sSMC consisted of chromosomes 6 and 20. Array CGH analysis showed gains of the 6p11.2q12 (9 Mb) and 20 p11.21 (3.3 Mb) chromosomal regions with a total of 42 genes present on both sSMC. Our findings support also the hypothesis that the modification of the expression of some genes involved in embryo implantation, like THBD gene, could be responsible in the recurrent abortions. This report underpins the necessity of array CGH for characterizing precisely sSMC and helping in genotype-phenotype correlations. Furthermore, a literature review on sSMC is included.

  3. Atypical supernumerary phantom limb and phantom limb pain in a patient with spinal cord injury: case report.

    Science.gov (United States)

    Choi, Ja Young; Kim, Hyo In; Lee, Kil Chan; Han, Zee-A

    2013-12-01

    Supernumerary phantom limb (SPL) resulting from spinal cord lesions are very rare, with only sporadic and brief descriptions in the literature. Furthermore, the reported cases of SPL typically occurred in neurologically incomplete spinal cord patients. Here, we report a rare case of SPL with phantom limb pain that occurred after traumatic spinal cord injury in a neurologically complete patient. After a traffic accident, a 43-year-old man suffered a complete spinal cord injury with a C6 neurologic level of injury. SPL and associated phantom limb pain occurred 6 days after trauma onset. The patient felt the presence of an additional pair of legs that originated at the hip joints and extended medially, at equal lengths to the paralyzed legs. The intensity of SPL and associated phantom limb pain subsequently decreased after visual-tactile stimulation treatment, in which the patient visually identified the paralyzed limbs and then gently tapped them with a wooden stick. This improvement continued over the 2 months of inpatient treatment at our hospital and the presence of the SPLs was reduced to 20% of the real paralyzed legs. This is the first comprehensive report on SPLs of the lower extremities after neurologically complete spinal cord injury.

  4. Dissociation of Axonal Neurofilament Content from Its Transport Rate.

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    Aidong Yuan

    Full Text Available The axonal cytoskeleton of neurofilament (NF is a long-lived network of fibrous elements believed to be a stationary structure maintained by a small pool of transported cytoskeletal precursors. Accordingly, it may be predicted that NF content in axons can vary independently from the transport rate of NF. In the present report, we confirm this prediction by showing that human NFH transgenic mice and transgenic mice expressing human NFL Ser55 (Asp develop nearly identical abnormal patterns of NF accumulation and distribution in association with opposite changes in NF slow transport rates. We also show that the rate of NF transport in wild-type mice remains constant along a length of the optic axon where NF content varies 3-fold. Moreover, knockout mice lacking NFH develop even more extreme (6-fold proximal to distal variation in NF number, which is associated with a normal wild-type rate of NF transport. The independence of regional NF content and NF transport is consistent with previous evidence suggesting that the rate of incorporation of transported NF precursors into a metabolically stable stationary cytoskeletal network is the major determinant of axonal NF content, enabling the generation of the striking local variations in NF number seen along axons.

  5. Functional complexity of the axonal growth cone: a proteomic analysis.

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    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  6. Calpain Inhibition Reduces Axolemmal Leakage in Traumatic Axonal Injury

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    János Sándor

    2009-12-01

    Full Text Available Calcium-induced, calpain-mediated proteolysis (CMSP has recently been implicated to the pathogenesis of diffuse (traumatic axonal injury (TAI. Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.

  7. Subtypes of GABAergic neurons project axons in the neocortex

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    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  8. A novel technique using hydrophilic polymers to promote axonal fusion

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    Ravinder Bamba

    2016-01-01

    Full Text Available The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day. When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily repaired. Polythethylene glycol (PEG in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.

  9. A novel technique using hydrophilic polymers to promote axonal fusion

    Institute of Scientific and Technical Information of China (English)

    Ravinder Bamba; D Colton Riley; Nathaniel D Kelm; Mark D Does; Richard D Dortch; Wesley P hTayer

    2016-01-01

    The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily re-paired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.

  10. Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording

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    Anders Victor ePetersen

    2015-10-01

    Full Text Available The axon initial segment (AIS is an essential neuronal compartment. It is usually where action potentials are initiated. Recent studies demonstrated that the AIS is a plastic structure that can be regulated by neuronal activity and by the activation of metabotropic receptors. Studying the AIS in live tissue can be difficult because its identification is not always reliable. Here we provide a new technique allowing a fast and reliable identification of the AIS in live brain slice preparations. By simultaneous recoding of extracellular local field potentials and whole-cell patch-clamp recording of neurons, we can detect sinks caused by inward currents flowing across the membrane. We determine the location of the AIS by comparing the timing of these events with the action potential. We demonstrate that this method allows the unequivocal identification of the AIS of different types of neurons from the brain.

  11. Neurofilament proteins in axonal regeneration and neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    Haitao Wang; Minfei Wu; Chuanjun Zhan; Enyuan Ma; Maoguang Yang; Xiaoyu Yang; Yingpu Li

    2012-01-01

    Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.

  12. Inflections in threshold electrotonus to depolarizing currents in sensory axons.

    Science.gov (United States)

    Burke, David; Howells, James; Trevillion, Louise; Kiernan, Matthew C; Bostock, Hugh

    2007-12-01

    Threshold electrotonus involves tracking the changes in axonal excitability produced by subthreshold polarizing currents and is the only technique that allows insight into the function of internodal conductances in human subjects in vivo. There is often an abrupt transient reversal of the threshold change as excitability increases in response to conditioning depolarizing currents (S1 phase). In recordings from motor axons, it has been recently demonstrated that this notch or inflection is due to activation of low-threshold axons. We report that a notch is frequently seen in sensory recordings (in 33 of 50 healthy subjects) using the standard threshold electrotonus protocol. When large, the notch can distort subsequent phases of threshold electrotonus and could complicate quantitative measurements and modeling studies.

  13. Pili canaliculi as manifestation of giant axonal neuropathy*

    Science.gov (United States)

    de Almeida Jr., Hiram Larangeira; Garcias, Gilberto; Silva, Ricardo Marques e; Batista, Stela Laner; Pasetto, Fernanda

    2016-01-01

    Giant axonal neuropathy is a rare autosomal recessive neurodegenerative disease. The condition is characterized by neurons with abnormally large axons due to intracellular filament accumulation. The swollen axons affect both the peripheral and central nervous system. A 6-year old female patient had been referred to a geneticist reporting problems with walking and hypotonia. At the age of 10, she became wheelchair dependent. Scanning electron microscopy of a curly hair classified it as pili canaliculi. GAN gene sequencing demonstrated mutation c.1456G>A (p.GLU486LYS). At the age of 12, the patient died due to respiratory complications. Dermatologists should be aware of this entity since hair changes are considered suggestive of GAN.

  14. Using quantum filters to process images of diffuse axonal injury

    Science.gov (United States)

    Pineda Osorio, Mateo

    2014-06-01

    Some images corresponding to a diffuse axonal injury (DAI) are processed using several quantum filters such as Hermite Weibull and Morse. Diffuse axonal injury is a particular, common and severe case of traumatic brain injury (TBI). DAI involves global damage on microscopic scale of brain tissue and causes serious neurologic abnormalities. New imaging techniques provide excellent images showing cellular damages related to DAI. Said images can be processed with quantum filters, which accomplish high resolutions of dendritic and axonal structures both in normal and pathological state. Using the Laplacian operators from the new quantum filters, excellent edge detectors for neurofiber resolution are obtained. Image quantum processing of DAI images is made using computer algebra, specifically Maple. Quantum filter plugins construction is proposed as a future research line, which can incorporated to the ImageJ software package, making its use simpler for medical personnel.

  15. The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.

    Science.gov (United States)

    Godzik, Katharina; Coleman, Michael P

    2015-04-01

    The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.

  16. 锥形束 CT在164例多生牙诊断中的应用研究%The application of CBCT in diagnosis of supernumerary teeth of 164 patients

    Institute of Scientific and Technical Information of China (English)

    戴昱; 黄盛兴; 陈圳华

    2015-01-01

    目的:探讨CBCT在多生牙的诊断和定位中的临床应用价值。方法以经CBCT发现的上下颌多生牙的164例患者的225颗多生牙为研究对象,分析多生牙的三维位置和类型。结果225颗多生牙全部显示,CBCT能清晰显示多生牙的数目、大小、位置、与邻近组织的关系。结论 CBCT能精确提示多生牙的影像信息,对多生牙的诊断及定位具有重要的指导意义。%Objective To evaluate the value of cone -beam CT ( CBCT) in the diagnosis and orientation of supernumerary teeth .Methods 225 supernumerary teeth of 164 patients examined by CBCT were included . The three-dimensional position and size were analyzed .Results 225 supernumerary teeth were totally clearly discovered, including the number, size, spatial location, and the relationship with the adjacent teeth and organizations .Conclusions Accurate three -dimensional information of supernumerary was provided by CBCT imaging, which is helpful for diagnosis and orientation of supernumerary teeth .

  17. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  18. Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Onozato, T; Nakahara, A; Suzuki-Kouyama, E; Hineno, A; Yasude, T; Nakamura, T; Yahikozawa, H; Watanabe, M; Kayanuma, K; Makishita, H; Ohara, S; Hashimoto, T; Higuchi, K; Sakai, T; Asano, K; Hashimoto, T; Kanno, H; Nakayama, J; Oyanagi, K

    2016-10-01

    Axonal aggregates of phosphorylated (p-) transactive response DNA-binding protein 43 kDa (TDP-43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin-fixed paraffin-embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. (i) Aggregates of p-TDP-43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p-TDP-43 in the axons showed two characteristic microscopic features - dash-like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p-neurofilaments, but p-neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p- and p-independent (i)-TDP-43, and almost all neurones had lost their nuclear TDP-43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP-43-immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p-TDP-43 deposition was evident. There are two types of axonal p-TDP-43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p-i-TDP-43 in the nuclei of postsynaptic neurones. © 2016 British Neuropathological Society.

  19. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  20. Tuning the orchestra: transcriptional pathways controlling axon regeneration

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    Andrea eTedeschi

    2012-01-01

    Full Text Available Trauma in the adult mammalian central nervous system leads to irreversible structural and functional impairment due to failed regeneration attempts. In contrast, neurons in the peripheral nervous system exhibit a greater regenerative ability. It has been proposed that an orchestrated sequence of transcriptional events controlling the expression of specific sets of genes may be the underlying basis of an early cell-autonomous regenerative response. Understanding whether transcriptional fine tuning, in parallel with strategies aimed at counteracting extrinsic impediments promotes axon re-growth following central nervous system injuries represents an exciting challenge for future studies. Transcriptional pathways controlling axon regeneration are presented and discussed in this review.

  1. Giant Axonal Neuropathy Among Two Siblings - A Case Report

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    John Jhon. K

    2001-01-01

    Full Text Available Giant axonal neuropathy is a rate disorder with an autosomal recessive inheritance. It should be differentiated from toxic neuropathies, and hereditary degenerative disorders of nervous system like Friedreich′s ataxia and HMSN. Thick curly hair, though may not be present always is a useful clinical clue to identify cases. Prognosis is generally poor though course of the illness is variable. We report here a clinically and hisopathologically characteristic familial case of giant axonal neuropathy, which occurred in a 17-year-old boy, and his 21-year-old sister.

  2. Rapid axonal transport in primate optic nerve. Distribution of pressure-induced interruption.

    Science.gov (United States)

    Radius, R L; Anderson, D R

    1981-04-01

    Six primate eyes were studied after four hours of elevated intraocular pressure. Tissue specimens from the region of the lamina cribrosa were examined in cross section by transmission electron microscopy. Interruption in fast orthograde and retrograde axonal transport was identified in individual axons by noting accumulation of membraneous microorganelles, such as mitochondria and microvesicles within axon cylinders. Although organelle accumulation varied from bundle to bundle, involvement of individual axons was diffuse across the extent of a specific axon bundle. This observation contradicts the apparent association of axonal transport block with crosswise-oriented trabecular beams at the level of the lamina cribrosa as seen in tissue specimens examined in longitudinal section. It also fails to support the notion that blocked axonal transport with elevated pressure is produced by kinking of axons at the lamina.

  3. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by q-space imaging.

    Directory of Open Access Journals (Sweden)

    Kouhei Kamiya

    Full Text Available PURPOSE: Previous studies suggest that compression and stretching of the corticospinal tract (CST potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH. Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI analysis. METHODS: Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( =  axon diameter and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively. RESULTS: Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p<0.001, whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups. CONCLUSION: Our results suggest that in patients with iNPH, the CST does not undergo irreversible axonal damage but is rather compressed and/or stretched owing to pressure from the enlarged ventricle. These analyses of axon diameter and intra-axonal fraction yield insights into microstructural alterations of the CST in iNPH.

  4. Absence of SARM1 Rescues Development and Survival of NMNAT2-Deficient Axons

    OpenAIRE

    Jonathan Gilley; Giuseppe Orsomando; Isabel Nascimento-Ferreira; Michael P. Coleman

    2015-01-01

    Summary SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes to NMNAT metabolites occur in injured SARM1-deficient axons despite their delayed degeneration and that axon degeneration specifically induced by NMNAT2 depletion requires SARM1. Strikingly, SARM1 deficiency also corrects axon outgrowth in mice lacking NMNAT2, i...

  5. Computational Analysis of Axonal Transport: A Novel Assessment of Neurotoxicity, Neuronal Development and Functions

    Directory of Open Access Journals (Sweden)

    Toshiyuki Gotoh

    2012-03-01

    Full Text Available Axonal transport plays a crucial role in neuronal morphogenesis, survival and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for monitoring this cellular process has been lacking. In order to better characterize the mechanisms involved in axonal transport, we formulate a novel computer-assisted monitoring system of axonal transport. Potential uses of this system and implications for future studies will be discussed.

  6. Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome in low-grade fibromyxoid sarcoma.

    Science.gov (United States)

    Bartuma, Hammurabi; Möller, Emely; Collin, Anna; Domanski, Henryk A; Von Steyern, Fredrik Vult; Mandahl, Nils; Mertens, Fredrik

    2010-06-01

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare, low-grade malignant soft tissue tumor that is often mistaken for either benign or more malignant tumor types. Commonly, this tumor affects young adults and typically arises in the deep proximal extremities or trunk with frequent recurrences and can metastasize to the lungs many years later. Most cases have a recurrent balanced translocation involving chromosomes 7 and 16, t(7;16)(q32-34;p11), which leads to the fusion of the FUS and CREB3L2 genes. However, supernumerary ring chromosomes have been identified in a subset of FUS/CREB3L2-positive LGFMS, but it has not yet been formally demonstrated that such ring chromosomes harbor the FUS/CREB3L2 fusion gene. Here, we report the genetic findings of a supernumerary ring chromosome from an LGFMS from a 77-year-old man. Chromosome banding analysis revealed a supernumerary ring chromosome, and further studies with fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the ring contained material from chromosomes 7 and 16, that the FUS gene was present in two rearranged copies, and that it expressed the FUS/CREB3L2 fusion gene. Moreover, an assessment of previously reported cases showed that tumors with ring chromosomes relapsed more often than tumors with a balanced t(7;16), suggesting that ring formation in LGFMS is correlated with tumor progression. Copyright 2010 Elsevier Inc. All rights reserved.

  7. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Lomholt, N D

    2000-01-01

    Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-alpha (TNFalpha), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia to p...

  8. Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Visser, N.A.

    2016-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP

  9. Traction Force and Tension Fluctuations During Axon Growth

    Directory of Open Access Journals (Sweden)

    Jamison ePolackwich

    2015-10-01

    Full Text Available Actively generated mechanical forces play a central role in axon growthand guidance, but the mechanisms that underly force generation andregulation in growing axons remain poorly understood. We reportmeasurements of the dynamics of traction stresses from growth cones ofactively advancing axons from postnatal rat DRG neurons. By tracking themovement of the growth cone and analyzing the traction stress field froma reference frame that moves with it, we are able to show that there isa clear and consistent average stress field that underlies the complexspatial stresses present at any one time. The average stress field hasstrong maxima on the sides of the growth cone, directed inward towardthe growth cone neck. This pattern represents a contractile stresscontained within the growth cone, and a net force that is balanced bythe axon tension. Using high time-resolution measurements of the growthcone traction stresses, we show that the stress field is composed offluctuating local stress peaks, with a large number peaks that live fora short time, a population of peaks whose lifetime distribution followsan exponential decay, and a small number of very long-lived peaks. Weshow that the high time-resolution data also reveal that the tensionappears to vary randomly over short time scales, roughly consistent withthe lifetime of the stress peaks, suggesting that the tensionfluctuations originate from stochastic adhesion dynamics.

  10. Drosophila Ryks and their roles in axon and muscle guidance

    NARCIS (Netherlands)

    Lahaye, Liza Lucia

    2015-01-01

    In the last decade it has become clear that a number of the molecular mechanisms that are required for proper navigation of axons in complex nervous systems are also employed to guide muscles to their appropriate attachment sites. Among the gene families that mediate these diverse processes is the R

  11. Pain in patients with chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Erdmann, P.G.; Genderen, F.R. van; Teunissen, L.L.; Notermans, N.C.; Lindeman, E.; Wijck, A.J.M. van; Meeteren, N.L.U. van

    2010-01-01

    Background/Aims: Pain in patients with chronic idiopathic axonal polyneuropathy (CIAP) has never been studied in detail. The aim of the study was to investigate the pain experienced by patients with CIAP, and to determine whether pain is associated with health-related quality of life (HRQoL).

  12. Quantifying mechanical force in axonal growth and guidance

    Directory of Open Access Journals (Sweden)

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  13. Life-or-death decisions upon axonal damage.

    Science.gov (United States)

    Roselli, Francesco; Caroni, Pico

    2012-02-01

    In this issue of Neuron, Hu et al. (2012) report that upon axonal damage, CHOP and XBP1 unfolded protein response pathways are not recruited equally and have opposite effects on neuronal survival. XBP1 pathway boosting may represent a valuable neuroprotective strategy.

  14. Drosophila Ryks and their roles in axon and muscle guidance

    NARCIS (Netherlands)

    Lahaye, Liza Lucia

    2015-01-01

    In the last decade it has become clear that a number of the molecular mechanisms that are required for proper navigation of axons in complex nervous systems are also employed to guide muscles to their appropriate attachment sites. Among the gene families that mediate these diverse processes is the R

  15. Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Visser, N.A.

    2016-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP w

  16. PTEN inhibition and axon regeneration and neural repair

    Institute of Scientific and Technical Information of China (English)

    Yosuke Ohtake; Umar Hayat; Shuxin Li

    2015-01-01

    The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to con-trol the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in con-ditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Im-portantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

  17. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Lomholt, N D;

    2000-01-01

    periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice...

  18. Axonal transport of thiamine in frog sciatic nerves in vitro.

    Science.gov (United States)

    Bergquist, J E; Hanson, M

    1983-03-01

    Thiamine has an essential and unknown function in nerve membranes. Administration of thiamine can alleviate symptoms of thiamine deficiency within a few hours. The time course is consistent with a fast axonal transport of the vitamin. Very little is known about axonal transport of low-molecular-weight substances with a preferential localization to the axon membrane. We investigated if labeled thiamine could be transported in the frog sciatic nerve. Radioactivity accumulated proximal to a ligature on the sciatic nerve after supplying the dorsal ganglia with [35S]thiamine in vitro. The accumulation was reduced by inhibition of the energy metabolism with dinitrophenol and by inhibition of protein synthesis in the ganglia with cycloheximide. Vinblastine did not affect the accumulation of thiamine at a concentration which was sufficient to block transport of [3H]leucine-labeled proteins. Accumulation distal to a ligature could be demonstrated in vivo but not in vitro after injecting the gastrocnemius muscle with labeled thiamine. Axonal transport of [3H]leucine-labeled proteins was inhibited by thiamine at millimolar concentrations in the incubation medium. A transient reduction of the compound action potential was obtained at these concentrations. Thiamine was migrating at a fast rate in frog sciatic nerves in both orthograde and retrograde directions. The uptake and/or transport was dependent on energy metabolism and a concomitant protein synthesis. The lack of effect by vinblastine suggests that the transported fraction of thiamine differs in subcellular localization from the bulk of transported [3H]leucine-labeled proteins.

  19. Investigation on the mechanism of peripheral axonal injury in glaucoma

    Directory of Open Access Journals (Sweden)

    Jun- Hong Zhao

    2013-05-01

    Full Text Available AIM: To compare the angles of longitudinal section of sclera around optic nerve heads and the never fiber layer changes in healthy adults and patients with glaucoma, and to investigate the mechanism of peripheral retinal axonal injury, with the combined knowledge of biomechanics. METHODS: The optical nerves and their peripheral tissue specimen in the 12 eyes from health adult donators and 12 eyes from glaucoma patient donators were dyed by Glees' method to compare the angles of longitudinal section of sclera around optic nerve heads(through optic nerve center, and to observe the anatomical features of the peripheral retinal axons. RESULTS: The mean angle of longitudinal section of sclera around optic nerve in healthy adults was 73.3°, while that in patients with absolute glaucoma was 75.6°. The difference showed no significance(t=1.44, P>0.05. There was a sharp bend in the course of peripheral optical fiber in healthy adults. However, the optic nerve fiber disappeared completely in patients with glaucoma end stage. CONCLUSION: The angle between the medial edge and leading edge of sclera(around optic nerve headsis an acute angle. The optical fiber in glaucoma end stage disappeared completely. The phenomenon may be related to high intraocular pressure, the sclera shape, the shear modulus of sclera and axons, and “axonal bending-injury” mechanism.

  20. Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Sally A Marik

    Full Text Available Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

  1. A small supernumerary marker chromosome present in a Turner syndrome patient not derived from X- or Y-chromosome: a case report

    OpenAIRE

    Vermeesch Joris; Andrieux Joris; Desai Manisha; Sheth Jayesh; Weise Anja; Kosyakova Nadezda; Ewers Elisabeth; Sheth Frenny; Hamid Ahmed B; Ziegler Monika; Liehr Thomas

    2009-01-01

    Abstract Background Small supernumerary marker chromosomes (sSMC) can be present in numerically abnormal karyotypes like in a 'Turner-syndrome karyotype' mos 45,X/46,X,+mar. Results Here we report the first case of an sSMC found in Turner syndrome karyotypes (sSMCT) derived from chromosome 14 in a Turner syndrome patient. According to cytogenetic and molecular cytogenetic characterization the karyotype was 46,X,+del(14)(q11.1). The present case is the third Turner syndrome case with an sSMCT ...

  2. The effect of virtual visual feedback on supernumerary phantom limb pain in a patient with high cervical cord injury: a single-case design study.

    Science.gov (United States)

    Katayama, Osamu; Iki, Hidemasa; Sawa, Shunji; Osumi, Michihiro; Morioka, Shu

    2015-01-01

    We characterized the effect of virtual visual feedback (VVF) on supernumerary phantom limb pain (SPLP) in a patient with high cervical cord injury. The subject was a 22-year-old man diagnosed with complete spinal cord injury (level C2) approximately 5 years ago. We applied the ABA'B' single-case design and set phases B and B' as intervention phases for comparison. SPLP significantly improved in comparison of phase A with phase B and phase A with phase B'. We suggest that VVF reduces SPLP and the effect lasts after VVF.

  3. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

    Directory of Open Access Journals (Sweden)

    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  4. Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.

    Science.gov (United States)

    Hutchins, B Ian; Li, Li; Kalil, Katherine

    2012-01-10

    Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

  5. Chronic excitotoxin-induced axon degeneration in a compartmented neuronal culture model

    Directory of Open Access Journals (Sweden)

    Katherine A Hosie

    2012-02-01

    Full Text Available Glutamate excitotoxicity is a major pathogenic process implicated in many neurodegenerative conditions, including AD (Alzheimer's disease and following traumatic brain injury. Occurring predominantly from over-stimulation of ionotropic glutamate receptors located along dendrites, excitotoxic axonal degeneration may also occur in white matter tracts. Recent identification of axonal glutamate receptor subunits within axonal nanocomplexes raises the possibility of direct excitotoxic effects on axons. Individual neuronal responses to excitotoxicity are highly dependent on the complement of glutamate receptors expressed by the cell, and the localization of the functional receptors. To enable isolation of distal axons and targeted excitotoxicity, murine cortical neuron cultures were prepared in compartmented microfluidic devices, such that distal axons were isolated from neuronal cell bodies. Within the compartmented culture system, cortical neurons developed to relative maturity at 11 DIV (days in vitro as demonstrated by the formation of dendritic spines and clustering of the presynaptic protein synaptophysin. The isolated distal axons retained growth cone structures in the absence of synaptic targets, and expressed glutamate receptor subunits. Glutamate treatment (100 μM to the cell body chamber resulted in widespread degeneration within this chamber and degeneration of distal axons in the other chamber. Glutamate application to the distal axon chamber triggered a lesser degree of axonal degeneration without degenerative changes in the untreated somal chamber. These data indicate that in addition to current mechanisms of indirect axonal excitotoxicity, the distal axon may be a primary target for excitotoxicity in neurodegenerative conditions.

  6. Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS

    NARCIS (Netherlands)

    Franssen, Elske H P; Zhao, Rong-Rong; Koseki, Hiroaki; Kanamarlapudi, Venkateswarlu; Hoogenraad, Casper C; Eva, Richard; Fawcett, James W

    2015-01-01

    Integrins are adhesion and survival molecules involved in axon growth during CNS development, as well as axon regeneration after injury in the peripheral nervous system (PNS). Adult CNS axons do not regenerate after injury, partly due to a low intrinsic growth capacity. We have previously studied

  7. Nicotine elicits prolonged calcium signaling along ventral hippocampal axons.

    Science.gov (United States)

    Zhong, Chongbo; Talmage, David A; Role, Lorna W

    2013-01-01

    Presynaptic nicotinic acetylcholine receptors (nAChRs) have long been implicated in the modulation of CNS circuits. We previously reported that brief exposure to low concentrations of nicotine induced sustained potentiation of glutamatergic transmission at ventral hippocampal (vHipp)-striatal synapses. Here, we exploited nAChR subtype-selective antagonists and agonists and α7*nAChR knockout mutant mice (α7-/-) to elucidate the signaling mechanisms underlying nAChR-mediated modulation of synaptic transmission. Using a combination of micro-slices culture from WT and α7-/-mice, calcium imaging, and immuno-histochemical techniques, we found that nicotine elicits localized and oscillatory increases in intracellular Ca(2+) along vHipp axons that persists for up to 30 minutes. The sustained phase of the nicotine-induced Ca(2+) response was blocked by α-BgTx but not by DHβE and was mimicked by α7*nAChR agonists but not by non-α7*nAChR agonists. In vHipp slices from α7-/- mice, nicotine elicited only transient increases of axonal Ca(2+) signals and did not activate CaMKII. The sustained phase of the nicotine-induced Ca(2+) response required localized activation of CaMKII, phospholipase C, and IP3 receptor mediated Ca(2+)-induced Ca(2+) release (CICR). In conclusion, activation of presynaptic nAChRs by nicotine elicits Ca(2+) influx into the presynaptic axons, the sustained phase of the nicotine-induced Ca(2+) response requires that axonal α7*nAChR activate a downstream signaling network in the vHipp axons.

  8. Pretarget sorting of retinocollicular axons in the mouse.

    Science.gov (United States)

    Plas, Daniel T; Lopez, Joshua E; Crair, Michael C

    2005-10-31

    The map of the retina onto the optic tectum is a highly conserved feature of the vertebrate visual system; the mechanism by which this mapping is accomplished during development is a long-standing problem of neurobiology. The early suggestion by Roger Sperry that the map is formed through interactions between retinal ganglion cell axons and target cells within the tectum has gained significant experimental support and widespread acceptance. Nonetheless, reports in a variety of species indicate that some aspects of retinotopic order exist within the optic tract, leading to the suggestion that this "preordering" of retinal axons may play a role in the formation of the mature tectal map. A satisfactory account of pretarget order must provide the mechanism by which such axon order develops. Insofar as this mechanism must ultimately be determined genetically, the mouse suggests itself as the natural species in which to pursue these studies. Quantitative and repeatable methods are required to assess the contribution of candidate genes in mouse models. For these reasons, we have undertaken a quantitative study of the degree of retinotopic order within the optic tract and nerve of wild-type mice both before and after the development of the retinotectal map. Our methods are based on tract tracing using lipophilic dyes, and our results indicate that there is a reestablishment of dorsoventral but not nasotemporal retinal order when the axons pass through the chiasm and that this order is maintained throughout the subsequent tract. Furthermore, this dorsoventral retinotopic order is well established by the day after birth, long before the final target zone is discernible within the tectum. We conclude that pretarget sorting of axons according to origin along the dorsoventral axis of the retina is both spatially and chronologically appropriate to contribute to the formation of the retinotectal map, and we suggest that these methods be used to search for the molecular basis of

  9. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

    Science.gov (United States)

    Colbert, C M; Johnston, D

    1996-11-01

    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  10. ALS Along the Axons – Expression of Coding and Noncoding RNA Differs in Axons of ALS models

    Science.gov (United States)

    Rotem, Nimrod; Magen, Iddo; Ionescu, Ariel; Gershoni-Emek, Noga; Altman, Topaz; Costa, Christopher J.; Gradus, Tal; Pasmanik-Chor, Metsada; Willis, Dianna E.; Ben-Dov, Iddo Z.; Hornstein, Eran; Perlson, Eran

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA). Further, the introduction of SOD1G93A and TDP43A315T, established ALS-related mutations, changed the subcellular expression and localization of RNAs within the neurons, showing a spatial specificity to either the soma or the axon. Altogether, we provide here the first combined inclusive profile of mRNA and miRNA expression in two ALS models at the subcellular level. These data provide an important resource for studies on the roles of local protein synthesis and axon degeneration in ALS and can serve as a possible target pool for ALS treatment. PMID:28300211

  11. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

    Science.gov (United States)

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi

    2016-09-08

    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP. © 2016

  12. IH activity is increased in populations of slow versus fast motor axons of the rat.

    Directory of Open Access Journals (Sweden)

    Chad eLorenz

    2014-09-01

    Full Text Available Much is known about the electrophysiological variation in motoneuron somata across different motor units. However comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague-Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (slow motor axons and the other group innervating the tibialis anterior (fast motor axons muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001 or 20% of axon threshold (Z = 2.67, p = 0.008. Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003. In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047 accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.

  13. Genetic study of axon regeneration with cultured adult dorsal root ganglion neurons.

    Science.gov (United States)

    Saijilafu; Zhou, Feng-Quan

    2012-08-17

    It is well known that mature neurons in the central nervous system (CNS) cannot regenerate their axons after injuries due to diminished intrinsic ability to support axon growth and a hostile environment in the mature CNS(1,2). In contrast, mature neurons in the peripheral nervous system (PNS) regenerate readily after injuries(3). Adult dorsal root ganglion (DRG) neurons are well known to regenerate robustly after peripheral nerve injuries. Each DRG neuron grows one axon from the cell soma, which branches into two axonal branches: a peripheral branch innervating peripheral targets and a central branch extending into the spinal cord. Injury of the DRG peripheral axons results in substantial axon regeneration, whereas central axons in the spinal cord regenerate poorly after the injury. However, if the peripheral axonal injury occurs prior to the spinal cord injury (a process called the conditioning lesion), regeneration of central axons is greatly improved(4). Moreover, the central axons of DRG neurons share the same hostile environment as descending corticospinal axons in the spinal cord. Together, it is hypothesized that the molecular mechanisms controlling axon regeneration of adult DRG neurons can be harnessed to enhance CNS axon regeneration. As a result, adult DRG neurons are now widely used as a model system to study regenerative axon growth(5-7). Here we describe a method of adult DRG neuron culture that can be used for genetic study of axon regeneration in vitro. In this model adult DRG neurons are genetically manipulated via electroporation-mediated gene transfection(6,8). By transfecting neurons with DNA plasmid or si/shRNA, this approach enables both gain- and loss-of-function experiments to investigate the role of any gene-of-interest in axon growth from adult DRG neurons. When neurons are transfected with si/shRNA, the targeted endogenous protein is usually depleted after 3-4 days in culture, during which time robust axon growth has already occurred

  14. The corpus callosum in primates: processing speed of axons and the evolution of hemispheric asymmetry

    Science.gov (United States)

    Phillips, Kimberley A.; Stimpson, Cheryl D.; Smaers, Jeroen B.; Raghanti, Mary Ann; Jacobs, Bob; Popratiloff, Anastas; Hof, Patrick R.; Sherwood, Chet C.

    2015-01-01

    Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry. PMID:26511047

  15. Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss of APP in Mouse Models

    Directory of Open Access Journals (Sweden)

    Karen D.B. Smith

    2010-07-01

    Full Text Available Amyloid precursor protein (APP is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport in the presence or absence of APP. In vivo axonal transport reduced significantly in the absence of functional APP. Overexpression of human wildtype tau maintained normal axonal transport and resulted in a transient compensation of axonal transport deficits in the absence of APP. Mutant R406Wtau in combination with the absence of APP compounded axonal transport deficits and these deficits persisted with age. These results indicate that APP is necessary for axonal transport, and overexpression of human wildtype tau can compensate for the absence of APP at an early age.

  16. Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.

    Directory of Open Access Journals (Sweden)

    Chi Wang Ip

    Full Text Available Mice overexpressing proteolipid protein (PLP develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.

  17. The importance of axonal undulation in diffusion MR measurements: a Monte Carlo simulation study.

    Science.gov (United States)

    Nilsson, Markus; Lätt, Jimmy; Ståhlberg, Freddy; van Westen, Danielle; Hagslätt, Håkan

    2012-05-01

    Many axons follow wave-like undulating courses. This is a general feature of extracranial nerve segments, but is also found in some intracranial nervous tissue. The importance of axonal undulation has previously been considered, for example, in the context of biomechanics, where it has been shown that posture affects undulation properties. However, the importance of axonal undulation in the context of diffusion MR measurements has not been investigated. Using an analytical model and Monte Carlo simulations of water diffusion, this study compared undulating and straight axons in terms of diffusion propagators, diffusion-weighted signal intensities and parameters derived from diffusion tensor imaging, such as the mean diffusivity (MD), the eigenvalues and the fractional anisotropy (FA). All parameters were strongly affected by the presence of undulation. The diffusivity perpendicular to the undulating axons increased with the undulation amplitude, thus resembling that of straight axons with larger diameters. Consequently, models assuming straight axons for the estimation of the axon diameter from diffusion MR measurements might overestimate the diameter if undulation is present. FA decreased from approximately 0.7 to 0.5 when axonal undulation was introduced into the simulation model structure. Our results indicate that axonal undulation may play a role in diffusion measurements when investigating, for example, the optic and sciatic nerves and the spinal cord. The simulations also demonstrate that the stretching or compression of neuronal tissue comprising undulating axons alters the observed water diffusivity, suggesting that posture may be of importance for the outcome of diffusion MRI measurements.

  18. Eph:ephrin-B1 forward signaling controls fasciculation of sensory and motor axons.

    Science.gov (United States)

    Luxey, Maëva; Jungas, Thomas; Laussu, Julien; Audouard, Christophe; Garces, Alain; Davy, Alice

    2013-11-15

    Axon fasciculation is one of the processes controlling topographic innervation during embryonic development. While axon guidance steers extending axons in the accurate direction, axon fasciculation allows sets of co-extending axons to grow in tight bundles. The Eph:ephrin family has been involved both in axon guidance and fasciculation, yet it remains unclear how these two distinct types of responses are elicited. Herein we have characterized the role of ephrin-B1, a member of the ephrinB family in sensory and motor innervation of the limb. We show that ephrin-B1 is expressed in sensory axons and in the limb bud mesenchyme while EphB2 is expressed in motor and sensory axons. Loss of ephrin-B1 had no impact on the accurate dorso-ventral innervation of the limb by motor axons, yet EfnB1 mutants exhibited decreased fasciculation of peripheral motor and sensory nerves. Using tissue-specific excision of EfnB1 and in vitro experiments, we demonstrate that ephrin-B1 controls fasciculation of axons via a surround repulsion mechanism involving growth cone collapse of EphB2-expressing axons. Altogether, our results highlight the complex role of Eph:ephrin signaling in the development of the sensory-motor circuit innervating the limb.

  19. Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons

    Science.gov (United States)

    Kirkpatrick, L. L.; Witt, A. S.; Payne, H. R.; Shine, H. D.; Brady, S. T.

    2001-01-01

    Altered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.

  20. Fine mapping of a supernumerary proleg mutant (E(Cs) -l) and comparative expression analysis of the abdominal-A gene in silkworm, Bombyx mori.

    Science.gov (United States)

    Chen, P; Tong, X-L; Li, D-D; Liang, P-F; Fu, M-Y; Li, C-F; Hu, H; Xiang, Z-H; Lu, C; Dai, F-Y

    2013-10-01

    Patterning and phenotypic variations of appendages in insects provide important clues on developmental genetics. In the silkworm Bombyx mori, morphological variations associated with the E complex, an analogue of the Drosophila melanogaster bithorax complex, mainly determine the shape and number of prolegs on abdominal segments. Here, we report the identification and characterization of the allele responsible for the supernumerary crescents and legs-like (E(Cs) -l) mutant, a model derived from spontaneous mutation of the E complex, with supernumerary legs and extra crescents. Fine mapping with 1605 individuals revealed a ∼68 kb sequence in the upstream intergenic region of B. mori abdominal-A (Bmabd-A) clustered with the E(Cs) -l locus. Quantitative real-time PCR (qRT-PCR) and Western blotting analyses disclosed a marked increase in Bmabd-A expression in the E(Cs) -l mutant at both the transcriptional and translational levels, compared to wild-type Dazao. Furthermore, we observed ectopic expression of the Bmabd-A protein in the second abdominal segment (A2) of the E(Cs) -l mutant. Our results collectively suggest that the 68 kb region contains important regulatory elements of the Bmabd-A gene, and provide evidence that the gene is required for limb development in abdominal segments in the silkworm.

  1. Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons.

    Science.gov (United States)

    del Castillo, Urko; Winding, Michael; Lu, Wen; Gelfand, Vladimir I

    2015-12-28

    In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides 'minus-end-out' microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.

  2. Effect of vesicle traps on traffic jam formation in fast axonal transport.

    Science.gov (United States)

    Kuznetsov, A V

    2010-08-01

    The purpose of this paper is to develop a model for simulation of the formation of organelle traps in fast axonal transport. Such traps may form in the regions of microtubule polar mismatching. Depending on the orientation of microtubules pointing toward the trap region, these traps can accumulate either plus-end or minus-end oriented vesicles. The model predicts that the maximum concentrations of organelles occur at the boundaries of the trap regions; the overall concentration of organelles in the axon with traps is greatly increased compared to that in a healthy axon, which is expected to contribute to mechanical damages of the axon. The organelle traps induce hindrance to organelle transport down the axon; the total organelle flux down the axon with traps is found to be significantly reduced compared to that in a healthy axon.

  3. Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans

    Science.gov (United States)

    Meng, Lingfeng; Zhang, Albert; Jin, Yishi; Yan, Dong

    2016-01-01

    Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions. DOI: http://dx.doi.org/10.7554/eLife.19510.001 PMID:27767956

  4. Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins.

    Science.gov (United States)

    Gainer, Harold; House, Shirley; Kim, Dong Sun; Chin, Hemin; Pant, Harish C

    2017-04-01

    When isolated squid giant axons are incubated in radioactive amino acids, abundant newly synthesized proteins are found in the axoplasm. These proteins are translated in the adaxonal Schwann cells and subsequently transferred into the giant axon. The question as to whether any de novo protein synthesis occurs in the giant axon itself is difficult to resolve because the small contribution of the proteins possibly synthesized intra-axonally is not easily distinguished from the large amounts of the proteins being supplied from the Schwann cells. In this paper, we reexamine this issue by studying the synthesis of endogenous neurofilament (NF) proteins in the axon. Our laboratory previously showed that NF mRNA and protein are present in the squid giant axon, but not in the surrounding adaxonal glia. Therefore, if the isolated squid axon could be shown to contain newly synthesized NF protein de novo, it could not arise from the adaxonal glia. The results of experiments in this paper show that abundant 3H-labeled NF protein is synthesized in the squid giant fiber lobe containing the giant axon's neuronal cell bodies, but despite the presence of NF mRNA in the giant axon no labeled NF protein is detected in the giant axon. This lends support to the glia-axon protein transfer hypothesis which posits that the squid giant axon obtains newly synthesized protein by Schwann cell transfer and not through intra-axonal protein synthesis, and further suggests that the NF mRNA in the axon is in a translationally repressed state.

  5. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    Directory of Open Access Journals (Sweden)

    Kimberly N. Capers

    2011-01-01

    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  6. Coevolution of axon guidance molecule Slit and its receptor Robo.

    Directory of Open Access Journals (Sweden)

    Qi Yu

    Full Text Available Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  7. Axon and muscle spindle hyperplasia in the myostatin null mouse.

    Science.gov (United States)

    Elashry, Mohamed I; Otto, Anthony; Matsakas, Antonios; El-Morsy, Salah E; Jones, Lisa; Anderson, Bethan; Patel, Ketan

    2011-02-01

    Germline deletion of the myostatin gene results in hyperplasia and hypertrophy of the tension-generating (extrafusal) fibres in skeletal muscle. As this gene is expressed predominantly in myogenic tissues it offers an excellent model with which to investigate the quantitative relationship between muscle and axonal development. Here we show that skeletal muscle hyperplasia in myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore- and hindlimbs. We show that axons within these nerves undergo hypertrophy. Furthermore, we provide evidence that the age-related neural atrophic process is delayed in the absence of myostatin. Finally, we show that skeletal muscle hyperplasia in the myostatin null mouse is accompanied by an increase in the number of muscle spindles (also called stretch receptors or proprioceptors). However, our work demonstrates that the mechanisms regulating intrafusal fibre hyperplasia and hypertrophy differ from those that control the aetiology of extrafusal fibres.

  8. Coevolution of axon guidance molecule Slit and its receptor Robo.

    Science.gov (United States)

    Yu, Qi; Li, Xiao-Tong; Zhao, Xiao; Liu, Xun-Li; Ikeo, Kazuho; Gojobori, Takashi; Liu, Qing-Xin

    2014-01-01

    Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  9. Intrinsic axonal growth and the drive for regeneration

    Directory of Open Access Journals (Sweden)

    Kevin J O'Donovan

    2016-10-01

    Full Text Available Following damage to the adult nervous system in conditions like stroke, spinal cord injury or traumatic brain injury, many neurons die and most of the remaining spared neurons fail to regenerate. Injured neurons fail to regrow both because of the inhibitory milieu in which they reside as well as a loss of the intrinsic growth capacity of the neurons. If we are to develop effective therapeutic interventions that promote functional recovery for the devastating injuries described above, we must not only better understand the molecular mechanisms of developmental axonal growth in hopes of re-activating these pathways in the adult, but at the same time be aware that re-activation of adult axonal growth may proceed via distinct mechanisms. With this knowledge in hand, promoting adult regeneration of central nervous system neurons can become a more tractable and realistic therapeutic endeavor.

  10. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

    OpenAIRE

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry; McCormick, David A.

    2015-01-01

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two o...

  11. Morphology of axonal transport abnormalities in primate eyes.

    OpenAIRE

    Radius, R L; Anderson, D. R.

    1981-01-01

    The ultrastructure of the retina and optic nerve head was studied in primate eyes after central retinal artery occlusion. Within 2 hours of the vascular occlusion the inner retinal layers undergo watery (isosmotic) swelling. This watery swelling of axons and astroglia extends into the nerve head as far back as the anterior boundary of the scleral lamina cribrosa. The swelling is increased 4 hours after the occlusion, and by 24 hours disintegration has occurred. At the optic nerve head mitocho...

  12. Estimating neuronal connectivity from axonal and dendritic density fields

    Science.gov (United States)

    van Pelt, Jaap; van Ooyen, Arjen

    2013-01-01

    Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic “mass.” A population mean “mass” density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population mean density

  13. Polyethylene glycol restores axonal conduction after corpus callosum transection.

    Science.gov (United States)

    Bamba, Ravinder; Riley, D Colton; Boyer, Richard B; Pollins, Alonda C; Shack, R Bruce; Thayer, Wesley P

    2017-05-01

    Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

  14. Polyethylene glycol restores axonal conduction after corpus callosum transection

    Directory of Open Access Journals (Sweden)

    Ravinder Bamba

    2017-01-01

    Full Text Available Polyethylene glycol (PEG has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA were used to measure mean firing rate (MFR and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05. These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

  15. Variability and Reliabiltiy in Axon Growth Cone Navigation Decision Making

    Science.gov (United States)

    Garnelo, Marta; Ricoult, Sébastien G.; Juncker, David; Kennedy, Timothy E.; Faisal, Aldo A.

    2015-03-01

    The nervous system's wiring is a result of axon growth cones navigating through specific molecular environments during development. In order to reach their target, growth cones need to make decisions under uncertainty as they are faced with stochastic sensory information and probabilistic movements. The overall system therefore exhibits features of whole organisms (perception, decision making, action) in the subset of a single cell. We aim to characterise growth cone navigation in defined nano-dot guidance cue environments, by using the tools of computational neuroscience to conduct ``molecular psychophysics.'' We start with a generative model of growth cone behaviour and we 1. characterise sensory and internal sources of noise contributing to behavioural variables, by combining knowledge of the underlying stochastic dynamics in cue sensing and the growth of the cytoskeleton. This enables us to 2. produce bottom-up lower limit estimates of behavioural response reliability and visualise it as probability distributions over axon growth trajectories. Given this information we can match our in silico model's ``psychometric'' decision curves with empirical data. Finally we use a Monte-Carlo approach to predict response distributions of axon trajectories from our model.

  16. Efficient simulations of tubulin-driven axonal growth.

    Science.gov (United States)

    Diehl, Stefan; Henningsson, Erik; Heyden, Anders

    2016-08-01

    This work concerns efficient and reliable numerical simulations of the dynamic behaviour of a moving-boundary model for tubulin-driven axonal growth. The model is nonlinear and consists of a coupled set of a partial differential equation (PDE) and two ordinary differential equations. The PDE is defined on a computational domain with a moving boundary, which is part of the solution. Numerical simulations based on standard explicit time-stepping methods are too time consuming due to the small time steps required for numerical stability. On the other hand standard implicit schemes are too complex due to the nonlinear equations that needs to be solved in each step. Instead, we propose to use the Peaceman-Rachford splitting scheme combined with temporal and spatial scalings of the model. Simulations based on this scheme have shown to be efficient, accurate, and reliable which makes it possible to evaluate the model, e.g. its dependency on biological and physical model parameters. These evaluations show among other things that the initial axon growth is very fast, that the active transport is the dominant reason over diffusion for the growth velocity, and that the polymerization rate in the growth cone does not affect the final axon length.

  17. Axon clinical chemistry analyzer evaluated according to ECCLS protocol.

    Science.gov (United States)

    Brenna, S; Prencipe, L

    1992-10-01

    We assessed the analytical performance of the Axon system (Bayer Diagnostici), according to the European Committee for Clinical Laboratory Standards guidelines, for assay of 12 analytes: cholesterol, creatinine, glucose, total protein, urea, uric acid, alkaline phosphatase, alpha-amylase, aspartate aminotransferase, creatine kinase, sodium, and potassium. The field evaluation lasted approximately 5 months and involved the collection of approximately 10,000 data points with the Axon. The following results were obtained: The highest CVs for controls and human sera at different concentration/activity values were 2.2% for within-run imprecision (n = 60; 3 days, pooled estimate) and 3.5% for the between-day imprecision (n = 20 days). Close correlation was found with results for patients' specimens assayed with comparative instruments (Hitachi 717 for substrates and enzymes, Beckman Synchron EL/E4A for electrolytes). No drift was observed during 8 h of operation. The linearity range was broad, sometimes exceeding the manufacturer's claims. No sample-, reagent-, or cuvette-related carryover was found. Measurement of control sera gave results within +/- 5% of the assigned values. We conclude that good reliability and practicability make the Axon system suitable for laboratories with various needs.

  18. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Yuta Iwai

    Full Text Available Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS, suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP amplitude (index of motor neuronal loss and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44, ALS patients (n = 140 had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p 5mV. Regression analyses showed that SDTC (R = -0.22 and depolarizing threshold electrotonus (R = -0.22 increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS.

  19. Prediction of Functional Outcome in Axonal Guillain-Barre Syndrome

    Science.gov (United States)

    2016-01-01

    Objective To identify the factors that could predict the functional outcome in patients with the axonal type of Guillain-Barre syndrome (GBS). Methods Two hundred and two GBS patients admitted to our university hospital between 2003 and 2014 were reviewed retrospectively. We defined a good outcome as being "able to walk independently at 1 month after onset" and a poor outcome as being "unable to walk independently at 1 month after onset". We evaluated the factors that differed between the good and poor outcome groups. Results Twenty-four patients were classified into the acute motor axonal neuropathy type. There was a statistically significant difference between the good and poor outcome groups in terms of the GBS disability score at admission, and GBS disability score and Medical Research Council sum score at 1 month after admission. In an electrophysiologic analysis, the good outcome group showed greater amplitude of median, ulnar, deep peroneal, and posterior tibial nerve compound muscle action potentials (CMAP) and greater amplitude of median, ulnar, and superficial peroneal sensory nerve action potentials (SNAP) than the poor outcome group. Conclusion A lower GBS disability score at admission, high amplitude of median, ulnar, deep peroneal, and posterior tibial CMAPs, and high amplitude of median, ulnar, and superficial peroneal SNAPs were associated with being able to walk at 1 month in patients with axonal GBS. PMID:27446785

  20. Inner membrane fusion mediates spatial distribution of axonal mitochondria

    Science.gov (United States)

    Yu, Yiyi; Lee, Hao-Chih; Chen, Kuan-Chieh; Suhan, Joseph; Qiu, Minhua; Ba, Qinle; Yang, Ge

    2016-01-01

    In eukaryotic cells, mitochondria form a dynamic interconnected network to respond to changing needs at different subcellular locations. A fundamental yet unanswered question regarding this network is whether, and if so how, local fusion and fission of individual mitochondria affect their global distribution. To address this question, we developed high-resolution computational image analysis techniques to examine the relations between mitochondrial fusion/fission and spatial distribution within the axon of Drosophila larval neurons. We found that stationary and moving mitochondria underwent fusion and fission regularly but followed different spatial distribution patterns and exhibited different morphology. Disruption of inner membrane fusion by knockdown of dOpa1, Drosophila Optic Atrophy 1, not only increased the spatial density of stationary and moving mitochondria but also changed their spatial distributions and morphology differentially. Knockdown of dOpa1 also impaired axonal transport of mitochondria. But the changed spatial distributions of mitochondria resulted primarily from disruption of inner membrane fusion because knockdown of Milton, a mitochondrial kinesin-1 adapter, caused similar transport velocity impairment but different spatial distributions. Together, our data reveals that stationary mitochondria within the axon interconnect with moving mitochondria through fusion and fission and that local inner membrane fusion between individual mitochondria mediates their global distribution. PMID:26742817

  1. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

    Science.gov (United States)

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex.

  2. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  3. Intra-axonal protein synthesis - a new target for neural repair?

    Directory of Open Access Journals (Sweden)

    Jeffery L Twiss

    2016-01-01

    Full Text Available Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  4. Intra-axonal protein synthesis - a new target for neural repair?

    Science.gov (United States)

    Twiss, Jeffery L; Kalinski, Ashley L; Sachdeva, Rahul; Houle, John D

    2016-09-01

    Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  5. Intra-axonal protein synthesis - a new target for neural repair?

    Institute of Scientific and Technical Information of China (English)

    Jeffery L Twiss; Ashley L Kalinski; Rahul Sachdeva; John D Houle

    2016-01-01

    Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthe-sis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been docu-mented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regen-erating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regen-erating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  6. In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging.

    Science.gov (United States)

    Cao, Xu; Wang, Haiqiong; Wang, Zhao; Wang, Qingyao; Zhang, Shuang; Deng, Yuanping; Fang, Yanshan

    2017-10-01

    Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochondria or axonal degeneration. Further, unlike in in vitro cultured neurons, we found that mitophagy rarely occurred in intact axons in vivo, even in aged animals. Furthermore, blocking overall mitophagy by knockdown of the core autophagy genes Atg12 or Atg17 had little effect on the turnover of axonal mitochondria or axonal integrity, suggesting that mitophagy is not required for axonal maintenance; this is regardless of whether the mitophagy is PINK1-Parkin dependent or independent. In contrast, downregulation of mitochondrial fission-fusion genes caused age-dependent axonal degeneration. Moreover, Opa1 expression in the fly head was significantly decreased with age, which may underlie the accumulation of fragmented mitochondria in aged axons. Finally, we showed that adult-onset, neuronal downregulation of the fission-fusion, but not mitophagy genes, dramatically accelerated features of aging. We propose that axonal mitochondria are maintained independently of mitophagy and that mitophagy-independent mechanisms such as fission-fusion may be central to the maintenance of axonal mitochondria and neural integrity during normal aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons.

    Science.gov (United States)

    Heintz, Tristan G; Heller, Janosch P; Zhao, Rongrong; Caceres, Alfredo; Eva, Richard; Fawcett, James W

    2014-11-01

    CNS axons have poor regenerative ability compared to PNS axons, and mature axons regenerate less well than immature embryonic axons. The loss of regenerative ability with maturity is accompanied by the setting up of a selective transport filter in axons, restricting the types of molecule that are present. We confirm that integrins (represented by subunits β1 and α5) are present in early cortical axons in vitro but are excluded from mature axons. Ribosomal protein and L1 show selective axonal transport through association with kinesin kif4A; we have therefore examined the hypothesis that integrin transport might also be in association with kif4A. Kif4A is present in all processes of immature cortical neurons cultured at E18, then downregulated by 14days in vitro, coinciding with the exclusion of integrin from axons. Kif4a co-localises with β1 integrin in vesicles in neurons and non-neuronal cells, and the two molecules co-immunoprecipitate. Knockdown of KIF4A expression with shRNA reduced the level of integrin β1 in axons of developing neurons and reduced neurite elongation on laminin, an integrin-dependent substrate. Overexpression of kif4A triggered apoptosis in neuronal and non-neuronal cells. In mature neurons expression of kif4A-GFP at a modest level did not kill the cells, and the kif4A was detectable in their axons. However this was not accompanied by an increase in integrin β1 axonal transport, suggesting that kif4A is not the only integrin transporter, and that integrin exclusion from axons is controlled by factors other than the kif4A level. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS.

    Science.gov (United States)

    Koch, J C; Tönges, L; Barski, E; Michel, U; Bähr, M; Lingor, P

    2014-05-15

    The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy.

  9. Sonic hedgehog regulates its own receptor on postcrossing commissural axons in a glypican1-dependent manner.

    Science.gov (United States)

    Wilson, Nicole H; Stoeckli, Esther T

    2013-08-07

    Upon reaching their intermediate target, the floorplate, commissural axons acquire responsiveness to repulsive guidance cues, allowing the axons to exit the midline and adopt a contralateral, longitudinal trajectory. The molecular mechanisms that regulate this switch from attraction to repulsion remain poorly defined. Here, we show that the heparan sulfate proteoglycan Glypican1 (GPC1) is required as a coreceptor for the Shh-dependent induction of Hedgehog-interacting protein (Hhip) in commissural neurons. In turn, Hhip is required for postcrossing axons to respond to a repulsive anteroposterior Shh gradient. Thus, Shh is a cue with dual function. In precrossing axons it acts as an attractive guidance molecule in a transcription-independent manner. At the same time, Shh binds to GPC1 to induce the expression of its own receptor, Hhip, which mediates the repulsive response of postcrossing axons to Shh. Our study characterizes a molecular mechanism by which navigating axons switch their responsiveness at intermediate targets.

  10. Coculture of elongated neuron axon with poly (D, L-lactide-co-glycolide) biomembrane in vitro

    Institute of Scientific and Technical Information of China (English)

    程飚; 陈峥嵘

    2004-01-01

    Objective: To elongate human nerve axon in culture and search for suitable support matrices for peripheral nervous system transplantation.Methods: Human embryo cortical neuronal cells,seeded on poly ( D, L-lactide-co-glycolide ) ( PLGA )membrane scaffolds, were elongated with a self-made neuro-axon extending device. The growth and morphological changes of neuron axons were observed to measure axolemmal permeability after elongation.Neurofilament protein was stained by immunohistochemical technique.Results: Human embryo neuron axon could be elongated and cultured on the PLGA membrane and retain their normal form and function.Conclusions: Three dimensional scaffolds with elongated neuron axon have the basic characteristics of artificial nerves, indicating a fundemental theory of nerve repair with elongated neuron axon.

  11. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

    DEFF Research Database (Denmark)

    Hoeber, Jan; Konig, Niclas; Trolle, Carl

    2017-01-01

    restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM......), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of MesoMIM...... prevented stem cell migration, “bridges” were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting...

  12. Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.

    Science.gov (United States)

    Ma, Marek

    2013-12-01

    Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed.

  13. Trafifc lights for axon growth:proteoglycans and their neuronal receptors

    Institute of Scientific and Technical Information of China (English)

    Yingjie Shen

    2014-01-01

    Axon growth is a central event in the development and post-injury plasticity of the nervous system. Growing axons encounter a wide variety of environmental instructions. Much like trafifc lights in controlling the migrating axons, chondroitin sulfate proteoglycans (CSPGs) and hepa-ran sulfate proteoglycans (HSPGs) often lead to“stop”and“go”growth responses in the axons, respectively. Recently, the LAR family and NgR family molecules were identified as neuronal receptors for CSPGs and HSPGs. These discoveries provided molecular tools for further study of mechanisms underlying axon growth regulation. More importantly, the identiifcation of these proteoglycan receptors offered potential therapeutic targets for promoting post-injury axon re-generation.

  14. ATP7A (Menkes Protein) functions in Axonal Targeting and Synaptogenesis

    OpenAIRE

    Meskini, Rajaâ El; Crabtree, Kelli L.; Cline, Laura B.; Mains, Richard E.; Eipper, Betty A.; Ronnett, Gabriele V.

    2007-01-01

    Menkes Disease (MD) is a neurodegenerative disorder caused by mutations in the copper transporter, ATP7A, a P-type ATPase. We previously used the olfactory system to demonstrate that ATP7A expression is developmentally, not constitutive, regulated, peaking during synaptogenesis when it is highly expressed in extending axons in a copper-independent manner. Although not known to be associated with axonal functions, we explored the possibility that the inability of mutant ATP7A to support axon o...

  15. Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

    OpenAIRE

    2008-01-01

    The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon regrowth, we analyzed cell growth control genes using a virus-assisted in vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathw...

  16. Sarm1-Mediated Axon Degeneration Requires Both SAM and TIR Interactions

    OpenAIRE

    Gerdts, Josiah; Summers, Daniel W; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2013-01-01

    Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile α-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is e...

  17. Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration

    OpenAIRE

    Tohyama Koujiro; Campbell Gregor; Lieberman A Robert; Siddiqui Samir; Wong Bernadette ZY; Shokouhi Bahman N; Anderson Patrick N

    2010-01-01

    Abstract Background Microglia/macrophages and lymphocytes (T-cells) accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. Results When neurons of ...

  18. Genetic Study of Axon Regeneration with Cultured Adult Dorsal Root Ganglion Neurons

    OpenAIRE

    Saijilafu,; Zhou, Feng-Quan

    2012-01-01

    It is well known that mature neurons in the central nervous system (CNS) cannot regenerate their axons after injuries due to diminished intrinsic ability to support axon growth and a hostile environment in the mature CNS1,2. In contrast, mature neurons in the peripheral nervous system (PNS) regenerate readily after injuries3. Adult dorsal root ganglion (DRG) neurons are well known to regenerate robustly after peripheral nerve injuries. Each DRG neuron grows one axon from the cell soma, which ...

  19. Excitability and firing behavior of single slow motor axons transmitting natural repetitive firing of human motoneurons.

    Science.gov (United States)

    Kudina, Lydia P; Andreeva, Regina E

    2017-08-01

    Excitability of motor axons is critically important for realizing their main function, i.e., transmitting motoneuron firing to muscle fibers. The present study was designed to explore excitability recovery and firing behavior in single slow axons transmitting human motoneuron firing during voluntary muscle contractions. The abductor digiti minimi, flexor carpi ulnaris, and tibialis anterior were investigated during threshold stimulation of corresponding motor nerves. Motor unit (MU) firing index in response to testing volleys evoking M-responses was used as a physiological measure of axonal excitability and its changes throughout a target interspike interval (ISI) were explored. It was shown that axons displayed an early irresponsive period (within the first ~2-5 ms of a target ISI) that was followed by a responsive period (for the next 5-17 ms of the ISI), in which MUs fired axonal doublets, and a later irresponsive period. At the beginning of the responsive period, M-responses showed small latency delays. However, since at that ISI moment, MUs displayed excitability recovery with high firing index, slight latency changes may be considered as a functionally insignificant phenomenon. The duration of axonal doublet ISIs did not depend on motoneuron firing frequencies (range 4.3-14.6 imp/s). The question of whether or not traditionally described axonal recovery excitability cycle is realistic in natural motor control is discussed. In conclusion, the present approach, exploring, for the first time, excitability recovery in single slow axons during motoneuron natural activation, can provide further insight into axonal firing behavior in normal states and diseases.NEW & NOTEWORTHY Excitability of single slow axons was estimated by motor unit firing index in response to motor nerve stimulation, and its changes throughout a target interspike interval were explored during transmitting human motoneuron natural firing. It was found that axons exhibited early irresponsive

  20. Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer’s Neurons

    OpenAIRE

    Lan Guo; Heng Du; Shiqiang Yan; Xiaoping Wu; Guy M. McKhann; John Xi Chen; Shirley ShiDu Yan

    2013-01-01

    Normal axonal mitochondrial transport and function is essential for the maintenance of synaptic function. Abnormal mitochondrial motility and mitochondrial dysfunction within axons are critical for amyloid β (Aβ)-induced synaptic stress and the loss of synapses relevant to the pathogenesis of Alzheimer's disease (AD). However, the mechanisms controlling axonal mitochondrial function and transport alterations in AD remain elusive. Here, we report an unexplored role of cyclophilin D (CypD)-depe...

  1. Impacted Lower Third Molar Fused with a Supernumerary Tooth —Diagnosis and Treatment Planning Using Cone-Beam Computed Tomography

    Science.gov (United States)

    Ferreira-Junior, Osny; de Ávila, Luciana Dorigatti; da Silva Sampieri, Marcelo Bonifácio; Dias-Ribeiro, Eduardo; Chen, Wei-liang; Fan, Song

    2009-01-01

    This paper reported a case of fusion between an impacted third molar and a supernumerary tooth, in which a surgical intervention was carried out, with the objective of removing the dental elements. The panoramic radiography was complemented by the Donovan's radiographic technique; but because of the proximity of the dental element to the mandibular ramus, it was not possible to have a final fusion diagnosis. Hence, the Cone-Beam Computed Tomography—which provides precise three-dimensional information—was used to determinate the fusion diagnosis and also to help in the surgical planning. In this case report we observed that the periapical, occlusal and panoramic were not able to show details which could only be examined through the cone-beam computed tomography. PMID:20690426

  2. A small supernumerary marker chromosome present in a Turner syndrome patient not derived from X- or Y-chromosome: a case report

    Directory of Open Access Journals (Sweden)

    Vermeesch Joris

    2009-11-01

    Full Text Available Abstract Background Small supernumerary marker chromosomes (sSMC can be present in numerically abnormal karyotypes like in a 'Turner-syndrome karyotype' mos 45,X/46,X,+mar. Results Here we report the first case of an sSMC found in Turner syndrome karyotypes (sSMCT derived from chromosome 14 in a Turner syndrome patient. According to cytogenetic and molecular cytogenetic characterization the karyotype was 46,X,+del(14(q11.1. The present case is the third Turner syndrome case with an sSMCT not derived from the X- or the Y-chromosome. Conclusion More comprehensive characterization of such sSMCT might identify them to be more frequent than only ~0.6% in Turner syndrome cases according to available data.

  3. A role for myosin VI in the localization of axonal proteins.

    Directory of Open Access Journals (Sweden)

    Tommy L Lewis

    2011-03-01

    Full Text Available In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targeting of neuronal proteins. Recently, the plus-end-directed motor Myosin Va was shown to play a critical role in targeting of transmembrane proteins to dendrites; however, the role of myosin motors in axonal targeting is unknown. Here we show that Myosin VI, a minus-end-directed motor, plays a vital role in the enrichment of proteins on the surface of axons. Engineering non-neuronal proteins to interact with Myosin VI causes them to become highly concentrated at the axonal surface in dissociated rat cortical neurons. Furthermore, disruption of either Myosin VI function or expression leads to aberrant dendritic localization of axonal proteins. Myosin VI mediates the enrichment of proteins on the axonal surface at least in part by stimulating dendrite-specific endocytosis, a mechanism that has been shown to underlie the localization of many axonal proteins. In addition, a version of Channelrhodopsin 2 that was engineered to bind to Myosin VI is concentrated at the surface of the axon of cortical neurons in mice in vivo, suggesting that it could be a useful tool for probing circuit structure and function. Together, our results indicate that myosins help shape the polarized distributions of both axonal and dendritic proteins.

  4. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Christian Witzel

    2015-01-01

    Full Text Available Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection. ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005 and the number of arborizing axons (21% vs. 16% P = 0.008 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  5. Evidence for the Role of MAP1B in Axon Formation

    Science.gov (United States)

    Gonzalez-Billault, Christian; Avila, Jesus; Cáceres, Alfredo

    2001-01-01

    Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a selective and significant inhibition of axon formation that reflects a delay in axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by decreased microtubule formation and dynamics, which is dramatic at the distal axonal segment, as well as in growth cones, where the more recently assembled microtubule polymer normally predominates. These neurons also have aberrant growth cone formation and increased actin-based protrusive activity. Taken together, this study provides direct evidence showing that by promoting microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial role in axon formation. PMID:11452005

  6. NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

    Science.gov (United States)

    Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

    2016-01-01

    Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

  7. Motor neuron synapse and axon defects in a C. elegans alpha-tubulin mutant.

    Directory of Open Access Journals (Sweden)

    Renee Baran

    Full Text Available Regulation of microtubule dynamics underlies many fundamental cellular mechanisms including cell division, cell motility, and transport. In neurons, microtubules play key roles in cell migration, axon outgrowth, control of axon and synapse growth, and the regulated transport of vesicles and structural components of synapses. Loss of synapse and axon integrity and disruption of axon transport characterize many neurodegenerative diseases. Recently, mutations that specifically alter the assembly or stability of microtubules have been found to directly cause neurodevelopmental defects or neurodegeneration in vertebrates. We report here the characterization of a missense mutation in the C-terminal domain of C. elegans alpha-tubulin, tba-1(ju89, that disrupts motor neuron synapse and axon development. Mutant ju89 animals exhibit reduction in the number and size of neuromuscular synapses, altered locomotion, and defects in axon extension. Although null mutations of tba-1 show a nearly wild-type pattern, similar axon outgrowth defects were observed in animals lacking the beta-tubulin TBB-2. Genetic analysis reveals that tba-1(ju89 affects synapse development independent of its role in axon outgrowth. tba-1(ju89 is an altered function allele that most likely perturbs interactions between TBA-1 and specific microtubule-associated proteins that control microtubule dynamics and transport of components needed for synapse and axon growth.

  8. Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons.

    Science.gov (United States)

    Rodriguez-Gil, Diego J; Bartel, Dianna L; Jaspers, Austin W; Mobley, Arie S; Imamura, Fumiaki; Greer, Charles A

    2015-05-05

    Odorant receptors (OR) are strongly implicated in coalescence of olfactory sensory neuron (OSN) axons and the formation of olfactory bulb (OB) glomeruli. However, when ORs are first expressed relative to basal cell division and OSN axon extension is unknown. We developed an in vivo fate-mapping strategy that enabled us to follow OSN maturation and axon extension beginning at basal cell division. In parallel, we mapped the molecular development of OSNs beginning at basal cell division, including the onset of OR expression. Our data show that ORs are first expressed around 4 d following basal cell division, 24 h after OSN axons have reached the OB. Over the next 6+ days the OSN axons navigate the OB nerve layer and ultimately coalesce in glomeruli. These data provide a previously unidentified perspective on the role of ORs in homophilic OSN axon adhesion and lead us to propose a new model dividing axon extension into two phases. Phase I is OR-independent and accounts for up to 50% of the time during which axons approach the OB and begin navigating the olfactory nerve layer. Phase II is OR-dependent and concludes as OSN axons coalesce in glomeruli.

  9. Regulation of Axonal Midline Guidance by Prolyl 4-Hydroxylation in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Torpe, Nanna; Pocock, Roger David John

    2014-01-01

    , little is known of its importance in the control of axon guidance. In a screen of prolyl 4-hydroxylase (P4H) mutants, we found that genetic removal of a specific P4H subunit, DPY-18, causes dramatic defects in C. elegans neuroanatomy. In dpy-18 mutant animals, the axons of specific ventral nerve cord......Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently...

  10. Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

    DEFF Research Database (Denmark)

    Colak, Dilek; Ji, Sheng-Jian; Porse, Bo T

    2013-01-01

    show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay...... (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3...

  11. Performing Axon Orientation Assays with Secreted Semaphorins and Other Guidance Cues.

    Science.gov (United States)

    Delloye-Bourgeois, Céline; Moret, Frédéric; Castellani, Valérie

    2017-01-01

    The guidance of axons within the developing nervous system is orchestrated by a variety of cues that successively and complementary attract or repel axons to achieve a stereotyped wiring of neural circuits. Here we present a version of a method that has been widely used to identify and characterize the effect of guidance cues on the orientation of axons. We describe the coculture, within a three-dimensional environment, of dorsal spinal cord explants together with a cell aggregate secreting a candidate cue and the method to quantify the effect of this cue on axon orientation.

  12. Thiazolidinediones Promote Axonal Growth through the Activation of the JNK Pathway

    Science.gov (United States)

    Quintanilla, Rodrigo A.; Godoy, Juan A.; Alfaro, Ivan; Cabezas, Deny; von Bernhardi, Rommy; Bronfman, Miguel; Inestrosa, Nibaldo C.

    2013-01-01

    The axon is a neuronal process involved in protein transport, synaptic plasticity, and neural regeneration. It has been suggested that their structure and function are profoundly impaired in neurodegenerative diseases. Previous evidence suggest that Peroxisome Proliferator-Activated Receptors-γ (PPARγ promote neuronal differentiation on various neuronal cell types. In addition, we demonstrated that activation of PPARγby thiazolidinediones (TZDs) drugs that selectively activate PPARγ prevent neurite loss and axonal damage induced by amyloid-β (Aβ). However, the potential role of TZDs in axonal elongation and neuronal polarity has not been explored. We report here that the activation of PPARγ by TZDs promoted axon elongation in primary hippocampal neurons. Treatments with different TZDs significantly increased axonal growth and branching area, but no significant effects were observed in neurite elongation compared to untreated neurons. Treatment with PPARγ antagonist (GW 9662) prevented TZDs-induced axonal growth. Recently, it has been suggested that the c-Jun N-terminal kinase (JNK) plays an important role regulating axonal growth and neuronal polarity. Interestingly, in our studies, treatment with TZDs induced activation of the JNK pathway, and the pharmacological blockage of this pathway prevented axon elongation induced by TZDs. Altogether, these results indicate that activation of JNK induced by PPARγactivators stimulates axonal growth and accelerates neuronal polarity. These novel findings may contribute to the understanding of the effects of PPARγ on neuronal differentiation and validate the use of PPARγ activators as therapeutic agents in neurodegenerative diseases. PMID:23741474

  13. Histone acetylation inhibitors promote axon growth in adult dorsal root ganglia neurons.

    Science.gov (United States)

    Lin, Shen; Nazif, Kutaiba; Smith, Alexander; Baas, Peter W; Smith, George M

    2015-08-01

    Intrinsic mechanisms that guide damaged axons to regenerate following spinal cord injury remain poorly understood. Manipulation of posttranslational modifications of key proteins in mature neurons could reinvigorate growth machinery after injury. One such modification is acetylation, a reversible process controlled by two enzyme families, the histone deacetylases (HDACs) and the histone acetyl transferases (HATs), acting in opposition. Whereas acetylated histones in the nucleus are associated with upregulation of growth-promoting genes, deacetylated tubulin in the axoplasm is associated with more labile microtubules, conducive to axon growth. This study investigates the effects of HAT and HDAC inhibitors on cultured adult dorsal root ganglia (DRG) neurons and shows that inhibition of HATs by anacardic acid or CPTH2 improves axon outgrowth, whereas inhibition of HDACs by TSA or tubacin inhibits axon growth. Anacardic acid increased the number of axons able to cross an inhibitory chondroitin sulfate proteoglycan border. Histone acetylation but not tubulin acetylation level was affected by HAT inhibitors, whereas tubulin acetylation levels were increased in the presence of the HDAC inhibitor tubacin. Although the microtubule-stabilizing drug taxol did not have an effect on the lengths of DRG axons, nocodazole decreased axon lengths. Determining the mechanistic basis will require future studies, but this study shows that inhibitors of HAT can augment axon growth in adult DRG neurons, with the potential of aiding axon growth over inhibitory substrates produced by the glial scar. © 2015 Wiley Periodicals, Inc.

  14. Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Jan Jessen Krut

    Full Text Available Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL (marker of neuronal injury, neopterin (intrathecal immunoactivation and CSF/Plasma albumin ratio (blood-brain barrier integrity were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200, HIV-associated dementia (HAD (n = 14 and on combinations antiretroviral treatment (cART (n = 85, and healthy controls (n = 204. 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation.While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups.Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further

  15. Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients

    Science.gov (United States)

    Price, Richard W.; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

    2014-01-01

    Background Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. Methods With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. Results While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Conclusions Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and

  16. Erbin is required for myelination in regenerated axons after injury

    OpenAIRE

    2012-01-01

    Neuregulin 1 (NRG1) is an axon-derived factor that is critical for Schwann cell (SC) development and myelinogenesis in a manner dependent on transmembrane tyrosine kinases ErbB2 and ErbB3. Recent studies suggest that NRG1 signaling plays a role in remyelination of regenerated nerves after injury. In this study, we investigated the role of Erbin, a protein that interacts with ErbB2 in remyelination of injured nerves. We show that Erbin expression increased dramatically in injured nerves. Myeli...

  17. Pyridoxine neuropathy in rats: specific degeneration of sensory axons.

    Science.gov (United States)

    Windebank, A J; Low, P A; Blexrud, M D; Schmelzer, J D; Schaumburg, H H

    1985-11-01

    When rats received pyridoxine in doses large enough to cause neuropathy in humans, the animals developed gait ataxia that subsided after the toxin was withdrawn. By using quantitative histologic techniques, we found axonal degeneration of sensory system fibers and that the fibers derived from the ventral root were spared. Although the degeneration approached the dorsal root ganglion, neurons in the ganglion did not degenerate. We found no early decrease in oxygen consumption of nerve, suggesting that impaired oxidative metabolism was not the primary event.

  18. Neuroprotective Effects of Citicoline in Diffuse Axonal Injuries

    OpenAIRE

    Firooz Salehpou; Ghaffar Shokouhi; Moslem Shakeri; Mohammad Shimia; Atta Mahdkhah; Ali Baradaran; Mohammad Taghi Imani; arhad Mirzaee; Aydin Kazempour Azar; Amir Mohammad Bazzazi; Hadi Mohammad Khanli

    2013-01-01

    Citicoline is a neuroprotective agent and fundamental item of phospholipid biosynthesis in cell walls. In this study, we aimed at examining the effect of citicoline in patients suffering from traumatic brain injury with Glasgow Coma Score (GCS) ≤ 8, and diffuse axonal injury (DAI) diagnosis. Efficacy of citicoline was evaluated by measurement of malondialdehyde (MDA) plasma levels as a marker of oxidative stress. Forty patients were randomly divided into two groups of cases (treated with citi...

  19. The corpus callosum in primates: processing speed of axons and the evolution of hemispheric asymmetry.

    Science.gov (United States)

    Phillips, Kimberley A; Stimpson, Cheryl D; Smaers, Jeroen B; Raghanti, Mary Ann; Jacobs, Bob; Popratiloff, Anastas; Hof, Patrick R; Sherwood, Chet C

    2015-11-07

    Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry. © 2015 The Author(s).

  20. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Rajiv Sainath

    Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

  1. RabGDI controls axonal midline crossing by regulating Robo1 surface expression

    Directory of Open Access Journals (Sweden)

    Philipp Melanie

    2012-11-01

    Full Text Available Abstract Background Axons navigate to their future synaptic targets with the help of choice points, intermediate targets that express axon guidance cues. Once they reach a choice point, axons need to switch their response from attraction to repulsion in order to move on with the next stage of their journey. The mechanisms underlying the change in axonal responsiveness are poorly understood. Commissural axons become sensitive to the repulsive activity of Slits when they cross the ventral midline of the CNS. Responsiveness to Slits depends on surface expression of Robo receptors. In Drosophila, Commissureless (Comm plays a crucial regulatory role in midline crossing by keeping Robo levels low on precommissural axons. Interestingly, to date no vertebrate homolog of comm has been identified. Robo3/Rig1 has been shown to control Slit sensitivity before the midline, but without affecting Robo1 surface expression. Results We had identified RabGDI, a gene linked to human mental retardation and an essential component of the vesicle fusion machinery, in a screen for differentially expressed floor-plate genes. Downregulation of RabGDI by in ovo RNAi caused commissural axons to stall in the floor plate, phenocopying the effect observed after downregulation of Robo1. Conversely, premature expression of RabGDI prevented commissural axons from entering the floor plate. Furthermore, RabGDI triggered Robo1 surface expression in cultured commissural neurons. Taken together, our results identify RabGDI as a component of the switching mechanism that is required for commissural axons to change their response from attraction to repulsion at the intermediate target. Conclusion RabGDI takes over the functional role of fly Comm by regulating the surface expression of Robo1 on commissural axons in vertebrates. This in turn allows commissural axons to switch from attraction to repulsion at the midline of the spinal cord.

  2. Abnormal morphology of myelin and axon pathology in murine models of multiple sclerosis.

    Science.gov (United States)

    Bando, Yoshio; Nomura, Taichi; Bochimoto, Hiroki; Murakami, Koichi; Tanaka, Tatsuhide; Watanabe, Tsuyoshi; Yoshida, Shigetaka

    2015-02-01

    Demyelination and axonal damage are responsible for neurological deficits in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. However, the pathology of axonal damage in MS is not fully understood. In this study, histological analysis of morphological changes of axonal organelles during demyelination in murine models was investigated by scanning electron microscopy (SEM) using an osmium-maceration method. In cuprizone-induced demyelination, SEM showed typical morphology of demyelination in the corpus callosum of mouse brain. In contrast, SEM displayed variations in ultrastructural abnormalities of myelin structures and axonal organelles in spinal cord white matter of experimental autoimmune encephalomyelitis (EAE) mice, an animal model of MS. Myelin detachment and excessive myelin formation were observed as typical morphological myelin abnormalities in EAE. In addition, well-developed axoplasmic reticulum-like structures and accumulated mitochondria were observed in tortuous degenerating/degenerated axons and the length of mitochondria in axons of EAE spinal cord was shorter compared with naïve spinal cord. Immunohistochemistry also revealed dysfunction of mitochondrial fusion/fission machinery in EAE spinal cord axons. Moreover, the number of Y-shaped mitochondria was significantly increased in axons of the EAE spinal cord. Axonal morphologies in myelin basic protein-deficient shiverer mice were similar to those in EAE. However, shiverer mice had "tortuous" (S-curve shaped mitochondria) and larger mitochondria compared with wild-type and EAE mice. Lastly, analysis of human MS patient autopsied brains also demonstrated abnormal myelin structures in demyelinating lesions. These results indicate that morphological abnormalities of myelin and axonal organelles play important role on the pathogenesis of axonal injury in demyelinating diseases.

  3. Depending on Its Nano-Spacing, ALCAM Promotes Cell Attachment and Axon Growth

    Science.gov (United States)

    Thelen, Karsten; Jaehrling, Steffen; Spatz, Joachim P.; Pollerberg, G. Elisabeth

    2012-01-01

    ALCAM is a member of the cell adhesion molecule (CAM) family which plays an important role during nervous system formation. We here show that the two neuron populations of developing dorsal root ganglia (DRG) display ALCAM transiently on centrally and peripherally projecting axons during the two phases of axon outgrowth. To analyze the impact of ALCAM on cell adhesion and axon growth, DRG single cells were cultured on ALCAM-coated coverslips or on nanopatterns where ALCAM is presented in physiological amino-carboxyl terminal orientation at highly defined distances (29, 54, 70, 86, and 137 nm) and where the interspaces are passivated to prevent unspecific protein deposition. Some axonal features (branching, lateral deviation) showed density dependence whereas others (number of axons per neuron, various axon growth parameters) turned out to be an all-or-nothing reaction. Time-lapse analyses revealed that ALCAM density has an impact on axon velocity and advance efficiency. The behavior of the sensory axon tip, the growth cone, partially depended on ALCAM density in a dose-response fashion (shape, dynamics, detachment) while other features did not (size, complexity). Whereas axon growth was equally promoted whether ALCAM was presented at high (29 nm) or low densities (86 nm), the attachment of non-neuronal cells depended on high ALCAM densities. The attachment of non-neuronal cells to the rather unspecific standard proteins presented by conventional implants designed to enhance axonal regeneration is a severe problem. Our findings point to ALCAM, presented as 86 nm pattern, for a promising candidate for the improvement of such implants since this pattern drives axon growth to its full extent while at the same time non-neuronal cell attachment is clearly reduced. PMID:23251325

  4. Bushen Yisui Capsule ameliorates axonal injury in experimental autoimmune encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Ling Fang; Lei Wang; Qi Zheng; Tao Yang; Hui Zhao; Qiuxia Zhang; Kangning Li; Li Zhou; Haiyang Gong; Yongping Fan

    2013-01-01

    A preliminary clinical study by our group demonstrated Bushen Yisui Capsule (formerly cal ed Er-huang Formula) in combination with conventional therapy is an effective prescription for the treat-ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re-mains unclear. In this study, a MOG 35-55-immunized C57BL/6 mouse model of experimental au-toimmune encephalomyelitis was intragastrical y administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim-mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of rege-neration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.

  5. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  6. A possible role for integrin signaling in diffuse axonal injury.

    Directory of Open Access Journals (Sweden)

    Matthew A Hemphill

    Full Text Available Over the past decade, investigators have attempted to establish the pathophysiological mechanisms by which non-penetrating injuries damage the brain. Several studies have implicated either membrane poration or ion channel dysfunction pursuant to neuronal cell death as the primary mechanism of injury. We hypothesized that traumatic stimulation of integrins may be an important etiological contributor to mild Traumatic Brain Injury. In order to study the effects of forces at the cellular level, we utilized two hierarchical, in vitro systems to mimic traumatic injury to rat cortical neurons: a high velocity stretcher and a magnetic tweezer system. In one system, we controlled focal adhesion formation in neurons cultured on a stretchable substrate loaded with an abrupt, one dimensional strain. With the second system, we used magnetic tweezers to directly simulate the abrupt injury forces endured by a focal adhesion on the neurite. Both systems revealed variations in the rate and nature of neuronal injury as a function of focal adhesion density and direct integrin stimulation without membrane poration. Pharmacological inhibition of calpains did not mitigate the injury yet the inhibition of Rho-kinase immediately after injury reduced axonal injury. These data suggest that integrin-mediated activation of Rho may be a contributor to the diffuse axonal injury reported in mild Traumatic Brain Injury.

  7. An analysis of conductance changes in squid axon.

    Science.gov (United States)

    MULLINS, L J

    1959-05-20

    The membrane of the squid axon is considered on the basis of a pore model in which the distribution of the pore sizes strongly favors K(+) transfer when there is no potential. Electrical asymmetry causes non-penetrating ions on the membrane capacitor to exert a mechanical force on both membrane surfaces and this force results in a deformation of the membrane pore system such that it assumes a distribution of sizes favoring the ions exerting mechanical force. The ions involved appear to be Ca(++) on the outside of the membrane and isethionate(-), (i(-)) on the inside; as Ca(++) is equivalent in size to Na(+), the charged membrane is potentially able to transfer Na(+), when the ions deforming the membrane pore distribution are removed. A depolarization of the membrane leads to an opening of pores that will allow Na(+) penetration and a release of the membrane from deformation. The pores revert to the zero-potential pore size distribution hence the Na permeability change is a transient. Calculation shows that the potassium conductance vs. displacement of membrane potential curve for the squid axon and the "inactivation" function, h, can be obtained directly from the assumed membrane distortion without the introduction of arbitrary parameters. The sodium conductance, because it is a transient, requires assumptions about the time constants with which ions unblock pores at the outside and the inside of the membrane.

  8. Selective optogenetic stimulation of cholinergic axons in neocortex.

    Science.gov (United States)

    Kalmbach, Abigail; Hedrick, Tristan; Waters, Jack

    2012-04-01

    Acetylcholine profoundly affects neocortical function, being involved in arousal, attention, learning, memory, sensory and motor function, and plasticity. The majority of cholinergic afferents to neocortex are from neurons in nucleus basalis. Nucleus basalis also contains projecting neurons that release other transmitters, including GABA and possibly glutamate. Hence, electrical stimulation of nucleus basalis evokes the release of a mixture of neurotransmitters in neocortex, and this lack of selectivity has impeded research on cholinergic signaling in neocortex. We describe a method for the selective stimulation of cholinergic axons in neocortex. We used the Cre-lox system and a viral vector to express the light-activated protein channelrhodopsin-2 in cholinergic neurons in nucleus basalis and their axons in neocortex. Labeled neurons depolarized on illumination with blue light but were otherwise unchanged. In anesthetized mice, illumination of neocortex desynchronized the local field potential, indicating that light evoked release of ACh. This novel technique will enable many new studies of the cellular, network, and behavioral physiology of ACh in neocortex.

  9. Tau phosphorylation affects its axonal transport and degradation

    Science.gov (United States)

    Rodríguez-Martín, Teresa; Cuchillo-Ibáñez, Inmaculada; Noble, Wendy; Nyenya, Fanon; Anderton, Brian H.; Hanger, Diane P.

    2013-01-01

    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of tau bound to microtubules and inhibited axonal transport of tau. To determine whether differential tau clearance is responsible for the increase in phosphomimic tau, we inhibited autophagy in neurons which resulted in a 3-fold accumulation of phosphomimic tau compared with wild type tau, and endogenous tau was unaffected. In autophagy-deficient mouse embryonic fibroblasts, but not in neurons, proteasomal degradation of phosphomutant tau was also reduced compared with wild type tau. Therefore, autophagic and proteasomal pathways are involved in tau degradation, with autophagy appearing to be the primary route for clearing phosphorylated tau in neurons. Defective autophagy might contribute to the accumulaton of tau in neurodegenerative diseases. PMID:23601672

  10. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.

    2009-01-01

    death; the markers of different DRG cell populations and cutaneous innervation were unchanged. These anatomical changes were reflected in a slowing of conduction velocity at the lower end of the A-fiber conduction velocity range and a new population of more rapidly conducting C-fibers that are likely...... cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood Udgivelsesdato: 2009/6/17...

  11. Shank3 is localized in axons and presynaptic specializations of developing hippocampal neurons and involved in the modulation of NMDA receptor levels at axon terminals.

    Science.gov (United States)

    Halbedl, Sonja; Schoen, Michael; Feiler, Marisa S; Boeckers, Tobias M; Schmeisser, Michael J

    2016-04-01

    Autism-related Shank1, Shank2, and Shank3 are major postsynaptic scaffold proteins of excitatory glutamatergic synapses. A few studies, however, have already indicated that within a neuron, the presence of Shank family members is not limited to the postsynaptic density. By separating axons from dendrites of developing hippocampal neurons in microfluidic chambers, we show that RNA of all three Shank family members is present within axons. Immunostaining confirms these findings as all three Shanks are indeed found within separated axons and further co-localize with well-known proteins of the presynaptic specialization in axon terminals. Therefore, Shank proteins might not only serve as postsynaptic scaffold proteins, but also play a crucial role during axonal outgrowth and presynaptic development and function. This is supported by our findings that shRNA-mediated knockdown of Shank3 results in up-regulation of the NMDA receptor subunit GluN1 in axon terminals. Taken together, our findings will have major implications for the future analysis of neuronal Shank biology in both health and disease. Shank1, Shank2, and Shank3 are major postsynaptic scaffold proteins of excitatory glutamatergic synapses strongly related to several neuropsychiatric disorders. However, a few studies have already implicated a functional role of the Shanks beyond the postsynaptic density (PSD). We here show that all three Shanks are localized in both axons and pre-synaptic specializiations of developing hippocampal neurons in culture. We further provide evidence that Shank3 is involved in the modulation of NMDA receptor levels at axon terminals. Taken together, our study will open up novel avenues for the future analysis of neuronal Shank biology in both health and disease.

  12. N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

    Directory of Open Access Journals (Sweden)

    Giorgi Kharebava

    2015-12-01

    Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

  13. Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum

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    Richards L.J.

    2002-01-01

    Full Text Available The corpus callosum is a large fiber tract that connects neurons in the right and left cerebral hemispheres. Agenesis of the corpus callosum (ACC is associated with a large number of human syndromes but little is known about why ACC occurs. In most cases of ACC, callosal axons are able to grow toward the midline but are unable to cross it, continuing to grow into large swirls of axons known as Probst bundles. This phenotype suggests that in some cases ACC may be due to defects in axonal guidance at the midline. General guidance mechanisms that influence the development of axons include chemoattraction and chemorepulsion, presented by either membrane-bound or diffusible molecules. These molecules are not only expressed by the final target but by intermediate targets along the pathway, and by pioneering axons that act as guides for later arriving axons. Midline glial populations are important intermediate targets for commissural axons in the spinal cord and brain, including the corpus callosum. The role of midline glial populations and pioneering axons in the formation of the corpus callosum are discussed. Finally the differential guidance of the ipsilaterally projecting perforating pathway and the contralaterally projecting corpus callosum is addressed. Development of the corpus callosum involves the coordination of a number of different guidance mechanisms and the probable involvement of a large number of molecules.

  14. Chondroitin sulfate proteoglycans negatively regulate the positioning of mitochondria and endoplasmic reticulum to distal axons.

    Science.gov (United States)

    Sainath, Rajiv; Armijo-Weingart, Lorena; Ketscheck, Andrea; Xu, Zhuxuan; Li, Shuxin; Gallo, Gianluca

    2017-09-13

    Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix that inhibit the extension and regeneration of axons. However, the underlying mechanism of action remains poorly understood. Mitochondria and endoplasmic reticulum (ER) are functionally inter-linked organelles important to axon development and maintenance. We report that CSPGs impair the targeting of mitochondria and ER to the growth cones of chicken embryonic sensory axons. The effect of CSPGs on the targeting of mitochondria is blocked by inhibition of the LAR receptor for CSPGs. The regulation of the targeting of mitochondria and ER to the growth cone by CSPGs is due to attenuation of PI3K signaling, which is known to be downstream of LAR receptor activation. Dynactin is a required component of the dynein motor complex that drives the normally occurring retrograde evacuation of mitochondria from growth cones. CSPGs elevate the levels of p150(Glu) dynactin found in distal axons, and inhibition of the interaction of dynactin with dynein increased axon lengths on CSPGs. CSPGs decreased the membrane potential of mitochondria, and pharmacological inhibition of mitochondria respiration at the growth cone independent of manipulation of mitochondria positioning impaired axon extension. Combined inhibition of dynactin and potentiation of mitochondria respiration further increased axon lengths on CSPGs relative to inhibition of dynactin alone. These data reveal that the regulation of the localization of mitochondria and ER to growth cones is a previously unappreciated aspect of the effects of CSPGs on embryonic axons. © 2017 Wiley Periodicals, Inc. Develop Neurobiol, 2017. © 2017 Wiley Periodicals, Inc.

  15. Integration of shallow gradients of Shh and Netrin-1 guides commissural axons.

    Science.gov (United States)

    Sloan, Tyler F W; Qasaimeh, Mohammad A; Juncker, David; Yam, Patricia T; Charron, Frédéric

    2015-03-01

    During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting.

  16. Polarized targeting of L1-CAM regulates axonal and dendritic bundling in vitro.

    Science.gov (United States)

    Barry, Joshua; Gu, Yuanzheng; Gu, Chen

    2010-11-01

    Proper axonal and dendritic bundling is essential for the establishment of neuronal connections and the synchronization of synaptic inputs, respectively. Cell adhesion molecules of the L1-CAM (L1-cell adhesion molecule) family regulate axon guidance and fasciculation, neuron migration, dendrite morphology, and synaptic plasticity. It remains unclear how these molecules play so many different roles. Here we show that polarized axon-dendrite targeting of an avian L1-CAM protein, NgCAM (neuron-glia cell adhesion molecule), can regulate the switch of bundling of the two major compartments of rat hippocampal neurons. Using a new in-vitro model for studying neurite-neurite interactions, we found that expressed axonal NgCAM induced robust axonal bundling via the trans-homophilic interaction of immunoglobulin domains. Interestingly, dendritic bundling was induced by the dendritic targeting of NgCAM, caused by either deleting its fibronectin repeats or blocking activities of protein kinases. Consistent with the NgCAM results, expression of mouse L1-CAM also induced axonal bundling and blocking kinase activities disrupted its axonal targeting. Furthermore, the trans-homophilic interaction stabilized the bundle formation, probably through recruiting NgCAM proteins to contact sites and promoting guided axon outgrowth. Taken together, our results suggest that precise localization of L1-CAM is important for establishing proper cell-cell contacts in neural circuits.

  17. Selective control of small versus large diameter axons using infrared laser light (Conference Presentation)

    Science.gov (United States)

    Lothet, Emilie H.; Shaw, Kendrick M.; Horn, Charles C.; Lu, Hui; Wang, Yves T.; Jansen, E. Duco; Chiel, Hillel J.; Jenkins, Michael W.

    2016-03-01

    Sensory information is conveyed to the central nervous system via small diameter unmyelinated fibers. In general, smaller diameter axons have slower conduction velocities. Selective control of such fibers could create new clinical treatments for chronic pain, nausea in response to chemo-therapeutic agents, or hypertension. Electrical stimulation can control axonal activity, but induced axonal current is proportional to cross-sectional area, so that large diameter fibers are affected first. Physiologically, however, synaptic inputs generally affect small diameter fibers before large diameter fibers (the size principle). A more physiological modality that first affected small diameter fibers could have fewer side effects (e.g., not recruiting motor axons). A novel mathematical analysis of the cable equation demonstrates that the minimum length along the axon for inducing block scales with the square root of axon diameter. This implies that the minimum length along an axon for inhibition will scale as the square root of axon diameter, so that lower radiant exposures of infrared light will selectively affect small diameter, slower conducting fibers before those of large diameter. This prediction was tested in identified neurons from the marine mollusk Aplysia californica. Radiant exposure to block a neuron with a slower conduction velocity (B43) was consistently lower than that needed to block a faster conduction velocity neuron (B3). Furthermore, in the vagus nerve of the musk shrew, lower radiant exposure blocked slow conducting fibers before blocking faster conducting fibers. Infrared light can selectively control smaller diameter fibers, suggesting many novel clinical treatments.

  18. The central role of mitochondria in axonal degeneration in multiple sclerosis.

    Science.gov (United States)

    Campbell, Graham R; Worrall, Joseph T; Mahad, Don J

    2014-12-01

    Neurodegeneration in multiple sclerosis (MS) is related to inflammation and demyelination. In acute MS lesions and experimental autoimmune encephalomyelitis focal immune attacks damage axons by injuring axonal mitochondria. In progressive MS, however, axonal damage occurs in chronically demyelinated regions, myelinated regions and also at the active edge of slowly expanding chronic lesions. How axonal energy failure occurs in progressive MS is incompletely understood. Recent studies show that oligodendrocytes supply lactate to myelinated axons as a metabolic substrate for mitochondria to generate ATP, a process which will be altered upon demyelination. In addition, a number of studies have identified mitochondrial abnormalities within neuronal cell bodies in progressive MS, leading to a deficiency of mitochondrial respiratory chain complexes or enzymes. Here, we summarise the mitochondrial abnormalities evident within neurons and discuss how these grey matter mitochondrial abnormalities may increase the vulnerability of axons to degeneration in progressive MS. Although neuronal mitochondrial abnormalities will culminate in axonal degeneration, understanding the different contributions of mitochondria to the degeneration of myelinated and demyelinated axons is an important step towards identifying potential therapeutic targets for progressive MS.

  19. A developmental timing switch promotes axon outgrowth independent of known guidance receptors.

    Directory of Open Access Journals (Sweden)

    Katherine Olsson-Carter

    2010-08-01

    Full Text Available To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and the "stemness" factor LIN-28--and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation.

  20. Inhibition of kinesin-5 improves regeneration of injured axons by a novel microtubule-based mechanism

    Institute of Scientific and Technical Information of China (English)

    Peter W. Baas; Andrew J. Matamoros

    2015-01-01

    Microtubules have been identiifed as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concerns that abnormally stabilizing microtubules may have only limited beneifts for regeneration, while at the same time may be detrimental to the normal work that microtubules perform for the axon. Kinesin-5 (also called kif11 or Eg5), a molecular motor protein best known for its crucial role in mitosis, acts as a brake on microtubule movements by other motor proteins in the axon. Drugs that inhibit kinesin-5, originally developed to treat cancer, result in greater mobility of microtubules in the axon and an overall shift in the forces on the microtubule array. As a result, the axon grows faster, retracts less, and more readily enters environments that are inhibitory to axonal regeneration. Thus, drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost axonal regeneration without the concerns that ac-company abnormal stabilization of the microtubule array. Even so, inhibiting kinesin-5 is not without its own caveats, such as potential problems with navigation of the regenerating axon to its target, as well as morphological effects on dendrites that could affect learning and memory if the drugs reach the brain.

  1. Axon-somatic back-propagation in detailed models of spinal alpha motoneurons

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    Pietro eBalbi

    2015-02-01

    Full Text Available Antidromic action potentials following distal stimulation of motor axons occasionally fail to invade the soma of alpha motoneurons in spinal cord, due to their passing through regions of high non-uniformity.Morphologically detailed conductance-based models of cat spinal alpha motoneurons have been developed, with the aim to reproduce and clarify some aspects of the electrophysiological behavior of the antidromic axon-somatic spike propagation. Fourteen 3D morphologically detailed somata and dendrites of cat spinal alpha motoneurons have been imported from an open-access web-based database of neuronal morphologies, NeuroMorpho.org, and instantiated in neurocomputational models. An axon hillock, an axonal initial segment and a myelinated axon are added to each model.By sweeping the diameter of the axonal initial segment (AIS and the axon hillock, as well as the maximal conductances of sodium channels at the AIS and at the soma, the developed models are able to show the relationships between different geometric and electrophysiological configurations and the voltage attenuation of the antidromically travelling wave.In particular, a greater than usually admitted sodium conductance at AIS is necessary and sufficient to overcome the dramatic voltage attenuation occurring during antidromic spike propagation both at the myelinated axon-AIS and at the AIS-soma transitions.

  2. Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF.

    Science.gov (United States)

    Pun, San; Santos, Alexandre Ferrão; Saxena, Smita; Xu, Lan; Caroni, Pico

    2006-03-01

    Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally defined selective vulnerabilities of distinct synapses or axons. Here we derive a quantitative topographic map of muscle innervation in the hindlimb. We show that in two mouse models of motoneuron disease (G93A SOD1 and G85R SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Axonal vulnerability leads to synaptic vesicle stalling and accumulation of BC12a1-a, an anti-apoptotic protein. It is alleviated by ciliary neurotrophic factor and triggers proteasome-dependent pruning of peripheral axon branches. Thus, motoneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.

  3. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...

  4. Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

    Directory of Open Access Journals (Sweden)

    Srinivasu Kallakuri

    2015-01-01

    Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

  5. Bimodal control of dendritic and axonal growth by the dual leucine zipper kinase pathway.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Knowledge of the molecular and genetic mechanisms underlying the separation of dendritic and axonal compartments is not only crucial for understanding the assembly of neural circuits, but also for developing strategies to correct defective dendrites or axons in diseases with subcellular precision. Previous studies have uncovered regulators dedicated to either dendritic or axonal growth. Here we investigate a novel regulatory mechanism that differentially directs dendritic and axonal growth within the same neuron in vivo. We find that the dual leucine zipper kinase (DLK signaling pathway in Drosophila, which consists of Highwire and Wallenda and controls axonal growth, regeneration, and degeneration, is also involved in dendritic growth in vivo. Highwire, an evolutionarily conserved E3 ubiquitin ligase, restrains axonal growth but acts as a positive regulator for dendritic growth in class IV dendritic arborization neurons in the larva. While both the axonal and dendritic functions of highwire require the DLK kinase Wallenda, these two functions diverge through two downstream transcription factors, Fos and Knot, which mediate the axonal and dendritic regulation, respectively. This study not only reveals a previously unknown function of the conserved DLK pathway in controlling dendrite development, but also provides a novel paradigm for understanding how neuronal compartmentalization and the diversity of neuronal morphology are achieved.

  6. NF-Protocadherin Regulates Retinal Ganglion Cell Axon Behaviour in the Developing Visual System.

    Directory of Open Access Journals (Sweden)

    Louis C Leung

    Full Text Available Cell adhesion molecules play a central role in mediating axonal tract development within the nascent nervous system. NF-protocadherin (NFPC, a member of the non-clustered protocadherin family, has been shown to regulate retinal ganglion cell (RGC axon and dendrite initiation, as well as influencing axonal navigation within the mid-optic tract. However, whether NFPC mediates RGC axonal behaviour at other positions within the optic pathway remains unclear. Here we report that NFPC plays an important role in RGC axonogenesis, but not in intraretinal guidance. Moreover, axons with reduced NFPC levels exhibit insensitivity to Netrin-1, an attractive guidance cue expressed at the optic nerve head. Netrin-1 induces rapid turnover of NFPC localized to RGC growth cones, suggesting that the regulation of NFPC protein levels may underlie Netrin-1-mediated entry of RGC axons into the optic nerve head. At the tectum, we further reveal a function for NFPC in controlling RGC axonal entry into the final target area. Collectively, our results expand our understanding of the role of NFPC in RGC guidance and illustrate that this adhesion molecule contributes to axon behaviour at multiple points in the optic pathway.

  7. Axonal transport rate decreased at the onset of optic neuritis in EAE mice.

    Science.gov (United States)

    Lin, Tsen-Hsuan; Kim, Joong Hee; Perez-Torres, Carlos; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H; Song, Sheng-Kwei

    2014-10-15

    Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+) accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.

  8. Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Praveena Manogaran

    2016-01-01

    Conclusions: The relationship between reductions in OCT measures of neuro-axonal health in the anterior visual pathway and MRI-based measures of myelin health in the posterior visual pathway suggests that these measures may be linked through bidirectional axonal degeneration.

  9. Inhibition of kinesin-5 improves regeneration of injured axons by a novel microtubule-based mechanism

    Directory of Open Access Journals (Sweden)

    Peter W Baas

    2015-01-01

    Full Text Available Microtubules have been identified as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concerns that abnormally stabilizing microtubules may have only limited benefits for regeneration, while at the same time may be detrimental to the normal work that microtubules perform for the axon. Kinesin-5 (also called kif11 or Eg5, a molecular motor protein best known for its crucial role in mitosis, acts as a brake on microtubule movements by other motor proteins in the axon. Drugs that inhibit kinesin-5, originally developed to treat cancer, result in greater mobility of microtubules in the axon and an overall shift in the forces on the microtubule array. As a result, the axon grows faster, retracts less, and more readily enters environments that are inhibitory to axonal regeneration. Thus, drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost axonal regeneration without the concerns that accompany abnormal stabilization of the microtubule array. Even so, inhibiting kinesin-5 is not without its own caveats, such as potential problems with navigation of the regenerating axon to its target, as well as morphological effects on dendrites that could affect learning and memory if the drugs reach the brain.

  10. Transfer of vesicles from Schwann cell to axon: a novel mechanism of communication in the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    María Alejandra eLopez-Verrilli

    2012-06-01

    Full Text Available Schwann cells (SCs are the glial component of the peripheral nervous system, with essential roles during development and maintenance of axons, as well as during regenerative processes after nerve injury. SCs increase conduction velocities by myelinating axons, regulate synaptic activity at presynaptic nerve terminals and are a source of trophic factors to neurons. Thus, development and maintenance of peripheral nerves are crucially dependent on local signalling between SCs and axons. In addition to the classic mechanisms of intercellular signalling, the possibility of communication through secreted vesicles has been poorly explored to date. Interesting recent findings suggest the occurrence of lateral transfer mediated by vesicles from glial cells to axons that could have important roles in axonal growth and axonal regeneration. Here, we review the role of vesicular transfer from SCs to axons and propose the benefits of this means in supporting neuronal and axonal maintenance and regeneration after nerve damage.

  11. Exposure to 1-bromopropane causes degeneration of noradrenergic axons in the rat brain.

    Science.gov (United States)

    Mohideen, Sahabudeen Sheik; Ichihara, Gaku; Ichihara, Sahoko; Nakamura, Shoji

    2011-07-11

    1-Bromopropane (1-BP) has been used as an alternative to ozone-depleting solvents. Previous studies showed that 1-BP is neurotoxic in animals and humans. In humans, exposure to 1-BP caused various neurological and neurobehavioral symptoms or signs including depressive or irritated mood. However, the neurobiological changes underlying the depressive symptoms induced by 1-BP remain to be determined. The depressive symptoms are thought to be associated with degeneration of axons containing noradrenaline and serotonin. Based on this hypothesis, the present study examined the effects of repeated exposure to 1-BP on serotonergic and noradrenergic axons. Exposure to 1-BP induced dose-dependent decreases in the density of noradrenergic axons in the rat prefrontal cortex, but no apparent change in the density of serotonergic axons. The results suggest that depressive symptoms in workers exposed to 1-BP are due, at least in part, to the degeneration of noradrenergic axons in the brain.

  12. Electromagnetic induction between axons and their schwann cell myelin-protein sheaths.

    Science.gov (United States)

    Goodman, G; Bercovich, D

    2013-12-01

    Two concepts have long dominated vertebrate nerve electrophysiology: (a) Schwann cell-formed myelin sheaths separated by minute non-myelinated nodal gaps and spiraling around axons of peripheral motor nerves reduce current leakage during propagation of trains of axon action potentials; (b) "jumping" by action potentials between successive nodes greatly increases signal conduction velocity. Long-held and more recent assumptions and issues underlying those concepts have been obscured by research emphasis on axon-sheath biochemical symbiosis and nerve regeneration. We hypothesize: mutual electromagnetic induction in the axon-glial sheath association, is fundamental in signal conduction in peripheral and central myelinated axons, explains the g-ratio and is relevant to animal navigation.

  13. BmRobo2/3 is required for axon guidance in the silkworm Bombyx mori.

    Science.gov (United States)

    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin

    2016-02-15

    Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidance molecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidance molecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm.

  14. The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis.

    Science.gov (United States)

    Zhao, Yan G; Sun, Le; Miao, Guangyan; Ji, Cuicui; Zhao, Hongyu; Sun, Huayu; Miao, Lin; Yoshii, Saori R; Mizushima, Noboru; Wang, Xiaoqun; Zhang, Hong

    2015-01-01

    WDR45/WIPI4, encoding a WD40 repeat-containing PtdIns(3)P binding protein, is essential for the basal autophagy pathway. Mutations in WDR45 cause the neurodegenerative disease β-propeller protein-associated neurodegeneration (BPAN), a subtype of NBIA. We generated CNS-specific Wdr45 knockout mice, which exhibit poor motor coordination, greatly impaired learning and memory, and extensive axon swelling with numerous axon spheroids. Autophagic flux is defective and SQSTM1 (sequestosome-1)/p62 and ubiquitin-positive protein aggregates accumulate in neurons and swollen axons. Nes-Wdr45(fl/Y) mice recapitulate some hallmarks of BPAN, including cognitive impairment and defective axonal homeostasis, providing a model for revealing the disease pathogenesis of BPAN and also for investigating the possible role of autophagy in axon maintenance.

  15. The course of axons through the retina and optic nerve head.

    Science.gov (United States)

    Radius, R L; Anderson, D R

    1979-06-01

    By identifying degenerating axons in tissue specimens from 22 primate eyes, it was possible to demonstrate the normal course of axon fibers. Nerve fiber bundles from a group of retinal ganglion cells travel together with little tendency to disperse laterally. In addition, axons are stratified such that processes from more central ganglion cells are successfully added to the inner strata of the retinal nerve fiber layer. Within and behind the lamina cribrosa, areas of degeneration following retinal photocoagulation were well circumscribed and confined to a group of adjacent axon bundles. This degree of retinotopic organization of axons within the nerve head and retinal fiber layer is believed to be consistent with the premise that isolated lesions within the lamina cribrosa could cause well-organized paracentral scotomas such as those characteristic of early glaucoma.

  16. PACSIN1, a Tau-interacting protein, regulates axonal elongation and branching by facilitating microtubule instability.

    Science.gov (United States)

    Liu, Yingying; Lv, Kaosheng; Li, Zenglong; Yu, Albert C H; Chen, Jianguo; Teng, Junlin

    2012-11-16

    Tau is a major member of the neuronal microtubule-associated proteins. It promotes tubulin assembly and stabilizes axonal microtubules. Previous studies have demonstrated that Tau forms cross-bridges between microtubules, with some particles located on cross-bridges, suggesting that some proteins interact with Tau and might be involved in regulating Tau-related microtubule dynamics. This study reports that PACSIN1 interacts with Tau in axon. PACSIN1 blockade results in impaired axonal elongation and a higher number of primary axonal branches in mouse dorsal root ganglia neurons, which is induced by increasing the binding ability of Tau to microtubules. In PACSIN1-blocked dorsal root ganglia neurons, a greater amount of Tau is inclined to accumulate in the central domain of growth cones, and it promotes the stability of the microtubule network. Taken together, these results suggest that PACSIN1 is an important Tau binding partner in regulating microtubule dynamics and forming axonal plasticity.

  17. 锥形束CT对埋伏多生牙定位的临床应用价值%Clinical application of cone-beam computer tomography in location of impacted supernumerary teeth

    Institute of Scientific and Technical Information of China (English)

    李辉; 王丽君; 李泽奎

    2012-01-01

    目的:探讨锥形束CT在埋伏多生牙定位中的应用价值.方法:对39例(42颗多生牙)经常规X线检查无法定位的埋伏多生牙患者做回顾性分析.经锥形束CT扫描,通过三维重建进行观察.结果:锥形束CT能准确定位多生牙的方向、数量及与邻近组织的空间位置关系.结论:锥形束CT可以直观、准确地对埋伏多生牙定位,对临床手术路径的确定、治疗方案的选择有重要应用价值.%Objective: To investigate the clinical application of cone-beam computer tomography in impacted supernumerary teeth location. Methods: 39 patients (with 42 supernumerary teeth) who had been examined by conventional X-ray examination with none location result, were scaned by cone-beam computer tomography and observed in three-dimensional reconstruction. Results: Cone-beam computer tomography possessed the advantages in three dimensional location,amount of the supernumerary teeth, and spital relationship with adjacent structures. Conclusion: Cone-beam computer tomography is intuitive and accurate positioning impacted supernumerary teeth, which has an important application value in surgical access option and treatment plan instruction.

  18. Interleukin (IL)-8 immunoreactivity of injured axons and surrounding oligodendrocytes in traumatic head injury.

    Science.gov (United States)

    Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru

    2016-06-01

    Interleukin (IL)-8 has been suggested to be a positive regulator of myelination in the central nervous system, in addition to its principal role as a chemokine for neutrophils. Immunostaining for beta-amyloid precursor protein (AβPP) is an effective tool for detecting traumatic axonal injury, although AβPP immunoreactivity can also indicate axonal injury due to hypoxic causes. In this study, we examined IL-8 and AβPP immunoreactivity in sections of corpus callosum obtained from deceased patients with blunt head injury and from equivalent control tissue. AβPP immunoreactivity was detected in injured axons, such as axonal bulbs and varicose axons, in 24 of 44 head injury cases. These AβPP immunoreactive cases had survived for more than 3h. The AβPP immunostaining pattern can be classified into two types: traumatic (Pattern 1) and non-traumatic (Pattern 2) axonal injuries, which we described previously [Hayashi et al. Int. J. Legal Med. 129 (2015) 1085-1090]. Three of 44 control cases also showed AβPP immunoreactive injured axons as Pattern 2. In contrast, IL-8 immunoreactivity was detected in 7 AβPP immunoreactive and in 2 non-AβPP immunoreactive head injury cases, but was not detected in any of the 44 control cases, including the 3 AβPP immunoreactive control cases. The IL-8 immunoreactive cases had survived from 3 to 24 days, whereas those cases who survived less than 3 days (n=29) and who survived 90 days (n=1) were not IL-8 immunoreactive. Moreover, IL-8 was detected as Pattern 1 axons only. In addition, double immunofluorescence analysis showed that IL-8 is expressed by oligodendrocytes surrounding injured axons. In conclusion, our results suggest that immunohistochemical detection of IL-8 may be useful as a complementary diagnostic marker of traumatic axonal injury.

  19. Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion

    Institute of Scientific and Technical Information of China (English)

    Lijuan Song; Yuehui Liu; YangYu; Xin Duan; Shening Qi; Yaobo Liu

    2012-01-01

    Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord,one of the most important nerve pathways for pain,sensory and motor functions.We provide evidence that ventral floor plate-secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medialto-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection.Downstream components of the Shh pathway,Patched 1 (Ptch1) and Smoothened (Smo),were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons.Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo.Using a co-culture assay,we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus.Prominent pathfinding errors of serotonergic RST axons were observed in various Shh,Ptch1 and Smo mutants.We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction,and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction.This is the first demonstration that Shh signalingmediated muitidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord.

  20. Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion.

    Science.gov (United States)

    Song, Lijuan; Liu, Yuehui; Yu, Yang; Duan, Xin; Qi, Shening; Liu, Yaobo

    2012-04-01

    Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord, one of the most important nerve pathways for pain, sensory and motor functions. We provide evidence that ventral floor plate-secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medial-to-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection. Downstream components of the Shh pathway, Patched 1 (Ptch1) and Smoothened (Smo), were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons. Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo. Using a co-culture assay, we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus. Prominent pathfinding errors of serotonergic RST axons were observed in various Shh, Ptch1 and Smo mutants. We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction, and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction. This is the first demonstration that Shh signaling-mediated multidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord.