RESUMO
OBJECTIVES: To evaluate immediate placement and immediate restoration of a novel implant with a 12°-angled prosthodontic platform, in fresh extraction sockets of the aesthetic zone of the maxilla. MATERIALS AND METHODS: Tapered, roughened surface implants of 4 mm (n=15) or 5 mm (n=13) diameter were placed in 27 participants (mean age: 47.1 years; range: 21-71 years) requiring an immediate replacement of single anterior maxillary teeth. Provisional screw-retained all-ceramic crowns were placed within 4 h following optical impressions. At 8 weeks (baseline), definitive screw-retained all-ceramic crowns were placed in occlusion. RESULTS: Twenty-six of the 28 implants met the inclusion criteria at surgery. Marginal bone levels revealed bone gain between surgery and baseline, and between baseline and 1 year of 0.2 mm (SD 0.75) and 0.78 mm (SD 2.45). Mean mid-buccal mucosal margins showed gains of 0.2 mm (SD 0.44). Prosthodontic maintenance and the aesthetics of the screw-retained implant crowns were facilitated by the external hex 12°-angled prosthodontic platform on the novel implant design, re-orientating the access cavity to the palatal or occlusal surfaces. All-ceramic implant crowns showed a high success rate with low maintenance issues over 1 year. CONCLUSION: Tapered, roughened-surfaced implants with a novel 12°-angled prosthodontic platform immediately placed in fresh extraction sockets, immediately restored with provisional crowns and subsequent definitive crowns at 8 weeks were successful for 1 year.
Assuntos
Coroas , Implantes Dentários para Um Único Dente , Porcelana Dentária , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Carga Imediata em Implante Dentário , Adulto , Idoso , Desenho Assistido por Computador , Dente Suporte , Implantação Dentária Endóssea/métodos , Retenção em Prótese Dentária , Restauração Dentária Temporária , Estética Dentária , Feminino , Humanos , Incisivo , Masculino , Maxila/cirurgia , Pessoa de Meia-Idade , Modelos Dentários , Estudos Prospectivos , Propriedades de Superfície , Alvéolo Dental/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.
Assuntos
Antiparkinsonianos/efeitos adversos , Carbidopa/efeitos adversos , Comportamento Compulsivo/induzido quimicamente , Delusões/induzido quimicamente , Alucinações/induzido quimicamente , Levodopa/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: Single implant crowns have become the preferred rehabilitation treatment option for replacing a missing tooth. PURPOSE: This study evaluates 5-year clinical success of using tilted implants placed immediately after extraction followed by rehabilitation with all-ceramic crowns. MATERIALS AND METHODS: Twenty-seven participants requiring 28 single implant crowns in the aesthetic zone of maxilla were recruited to participate in a single-arm clinical trial. All participants were rehabilitated according to immediate implant placement using CP grade 4 titanium implants with roughened surfaces and a 12°-angled platform. Provisional implant crowns were connected within 4 hours of implant placement and loaded according to progressive loading protocol. At 8 weeks (baseline), definitive screw-retained crowns fabricated using densely sintered zirconia abutments with the veneering porcelain were delivered. Participants were followed up to 5 years and 16 participants with 17 single implant crowns attended Year 5 recall. Data collection included changes in marginal bone levels (MBLs), mid-buccal mucosal levels (MBMLs), implant stability quotient (ISQ) values, and any prosthodontic maintenance issues. RESULTS: The mean changes in MBLs at each recall was bone fill of 0.5 ± 1.18 mm (surgery-baseline), increase of 0.1 ± 0.57 mm (baseline-Year 1), and marginal bone loss of 0.1 ± 0.25 mm (Years 1-5). A minimal change occurred with the MBMLs during the observation period. The mean ISQ value at each time point increased from 65.1 (implant placement), to 67.4 (baseline) and 69.9 (Years 1 and 5). Prosthodontic maintenance issues occurred only during the first year which included fracture of veneering ceramic and zirconia abutment as well as aesthetic concerns. CONCLUSIONS: Within the limitations of this study, the data collected would suggest that replacing a single missing tooth using titanium oral implants with 12° platform tilt and zirconia abutments can be a successful rehabilitation option in the esthetically demanding zone of anterior maxilla.
Assuntos
Perda do Osso Alveolar , Implantes Dentários para Um Único Dente , Carga Imediata em Implante Dentário , Maxila , Coroas , Prótese Dentária Fixada por Implante , Estética Dentária , Seguimentos , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
We show that rat retinal ganglion cell axons exhibit no topographic specificity in growth along the rostral-caudal axis of the embryonic superior colliculus (SC). Position-related, morphological differences are not found between temporal and nasal axon growth cones. However, embryonic retinal axons respond in vitro to a position-dependent molecular property of SC membranes. In vivo, regional specificity in side branching is the earliest indication that axons make topographic distinctions along the rostral-caudal SC axis. Our contrasting in vivo and in vitro results indicate that molecules encoding rostral-caudal position in the SC neither guide nor restrict retinal axon growth, but may promote the development of topographic connections by controlling specificity in the extension or stabilization of branches.
Assuntos
Axônios/fisiologia , Retina/embriologia , Células Ganglionares da Retina/ultraestrutura , Colículos Superiores/embriologia , Animais , Axônios/ultraestrutura , Carbocianinas , Membrana Celular/fisiologia , Corantes Fluorescentes , Idade Gestacional , Neuritos/fisiologia , Neuritos/ultraestrutura , Ratos , Ratos Sprague-Dawley , Retina/ultraestrutura , Células Ganglionares da Retina/fisiologia , Colículos Superiores/fisiologiaRESUMO
We examined in rats the relationship between the ordering of retinal axons in the optic pathway and the formation of a retinotopically organized projection to their primary target, the contralateral superior colliculus (SC). We have previously found that axons labeled by focal injections of 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) made in temporal or nasal retina of perinatal rats commonly mistarget along the medial-lateral and rostral-caudal axes of the SC. By postnatal day (P) 11-12, the retinocollicular projection attains an adult-like topography. Incorrectly targeted axons or axon segments are removed; axons that persist terminate in the topographically appropriate part of the SC (Simon and O'Leary: Dev Biol 137:125, 1990). In the present study, we made similar DiI injections, covering less than 2% of the retinal area, in peripheral temporal, nasal, superior, or inferior retina, in rats of two age groups, embryonic day (E) 21 to P (postnatal day) 2 and P11-P17. Whole mounts of retina, optic nerve and tract, and SC, and cross sections of the optic nerve, were examined. In E21-P2 rats, retinal axons labeled from each retinal site are diffusely distributed in the SC, and poorly ordered in the optic pathway. In retina, labeled axons travel in fascicles directly from the injection site to the optic disc, but neighbor relationships begin to degrade as fascicles split and mix. Retinotopic order is virtually lost in the optic nerve; axons labeled from each injection site disperse throughout its cross-sectional area, but the labeled axons tend to be concentrated toward a specific half of the nerve depending upon their retinal origin. This slight tendency toward retinotopic order increases in the optic tract, but axons are still poorly ordered as they leave the tract and enter the SC. Targeting errors along the medial-lateral axis of the SC, but apparently not along its rostral-caudal axis, are related to the positioning of axons across the width of the optic tract. In P11-P17 rats, axons labeled from each injection site arborize only in a small, topographically correct part of the SC. However, the distributions of labeled retinal axons observed in whole mounts of the retina and optic pathway have a degree of disorder similar to those in E21-P2 rats. Further, the scatter of labeled axons in optic nerve cross sections is comparable in both age groups. Therefore, the emergence of topographic order in the retinocollicular projection is not accompanied by an emergence of a retinotopic ordering of axons in the optic nerve.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Axônios/ultraestrutura , Retina/citologia , Visão Ocular/fisiologia , Animais , Mapeamento Encefálico , Carbocianinas , Embrião de Mamíferos/citologia , Feminino , Idade Gestacional , Vias Neurais/ultraestrutura , Nervo Óptico/ultraestrutura , Gravidez , Ratos , Ratos Endogâmicos , Rodaminas , Colículos Superiores/citologiaRESUMO
OBJECTIVE: To identify mitochondrial DNA (mtDNA) mutations that predispose to PD. BACKGROUND: Mitochondrial complex I activity is deficient in PD. mtDNA mutations may account for the defect, but the specific mutations have not been identified. METHODS: Complete sequencing was performed of all mtDNA-encoded complex I and transfer RNA (tRNA) genes in 28 PD patients and 8 control subjects, as well as screening of up to 243 additional PD patients and up to 209 control subjects by restriction digests for selected mutations. RESULTS: In the PD patients, 15 complex I missense mutations and 9 tRNA mutations were identified. After screening additional subjects, rare PD patients were found to carry complex I mutations that altered highly conserved amino acids. However, no significant differences were found in the frequencies of any mutations in PD versus control groups. The authors were unable to confirm previously reported associations of mutations at nucleotide positions (np) 4336, 5460, and 15927/8 with PD. Complex I mutations previously linked to Leber's hereditary optic neuropathy, one of which has been linked to atypical parkinsonism, were not associated with PD. CONCLUSIONS: mtDNA mutations with a high mutational burden (present in a high percentage of mtDNA molecules in an individual) in complex I or tRNA genes do not play a major role in the risk of PD in most PD patients. Further investigations are necessary to determine if any of the rare mtDNA mutations identified in PD patients play a role in the pathogenesis of PD in those few cases.
Assuntos
DNA Mitocondrial/genética , Mutação de Sentido Incorreto/genética , Doença de Parkinson/genética , RNA de Transferência/genética , Humanos , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To investigate a family with maternally inherited, adult-onset multisystem degeneration including prominent parkinsonism to determine whether clinical features can result from a mitochondrial DNA (mtDNA) mutation. The parkinsonism was levodopa responsive and was associated with the loss of pigmented neurons in the substantia nigra in at least one patient. BACKGROUND: Mitochondrial dysfunction is hypothesized to play a role in late-onset neurodegenerative diseases including PD and AD. Mitochondrial genetic mutations are hypothesized to account for these defects, but attempts to identify specific mtDNA mutations have been inconclusive. METHODS: Clinical examinations, DNA sequencing, and restriction digestion and biochemical analyses were performed. RESULTS: Maternal relatives harbor a G-to-A missense mutation, heteroplasmic in some patients, at nucleotide position 11778 of the mitochondrial ND4 gene of complex I that converts a highly conserved arginine to a histidine. Sequencing of the entire mitochondrial genome in an affected family member reveals no other mutations likely to be pathogenic. This mutation has been identified previously only in families with Leber's hereditary optic neuropathy-a disorder also linked to complex I dysfunction but usually limited clinically to optic atrophy. CONCLUSIONS: These data reveal previously unsuspected clinical heterogeneity of the G11778A mutation, and suggest that an inherited mtDNA mutation can contribute to the development of adult-onset parkinsonism and multisystem degeneration.
Assuntos
DNA Mitocondrial/genética , Transtornos Parkinsonianos/genética , Mutação Puntual/genética , Sequência de Bases/genética , Encéfalo/patologia , Feminino , Genoma , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/patologia , LinhagemRESUMO
Intrahippocampal grafts of fetal basal forebrain tissue have been shown to restore several aspects of neural function, including some degree of behavioral recovery in spatial memory tasks, in rats with fimbria-fornix lesions. Place fields, the behavioral correlates of complex-spike unit activity recorded in the hippocampus of rats, are altered by fimbria-fornix lesions, and provide an important measure of the functioning circuitry of the hippocampus after grafts. To investigate the effects of grafts on hippocampal circuitry, complex-spike units were recorded while the rats traversed a radial maze. Quantitative analyses of spatial activity showed that units in normal rats had spatially clustered, reliable place fields that were stable despite alterations of the maze. In contrast, units in rats with fimbria-fornix lesions had more dispersed, less reliable place fields that were disrupted when the maze was covered or rotated. Compared to rats with fimbria-fornix lesions, rats with grafts and units with more tightly clustered, more reliable, and more stable place fields when the maze was altered. The results suggest that: (1) fimbria-fornix lesions disrupt some aspects of complex-spike place field activity; (2) the functioning of hippocampal circuitry is influenced by fetal basal forebrain grafts; and (3) the grafts may ameliorate the effects of lesions on spatial behaviors by influencing critical aspects of place field activity in the hippocampus.
Assuntos
Lobo Frontal/transplante , Hipocampo/fisiologia , Memória/fisiologia , Comportamento Espacial , Potenciais de Ação , Animais , Feminino , Lobo Frontal/fisiologia , Ratos , Ratos EndogâmicosRESUMO
Topographic order in the rat retinocollicular projection emerges from an initially diffuse projection during an early postnatal remodeling period that is coincident with the period of naturally occurring ganglion cell death. Here, we examine the relationship between a retinal axon's position along the medial-lateral axis as it enters the superior colliculus (SC) and its ability to form an appropriately positioned arbor and survive the remodeling period. At E18-E19, prior to map remodeling, axons labeled with focal DiI injections in the periphery of temporal, nasal, superior or inferior retina are widespread along the medial-lateral SC axis. At P12, after remodeling, the distributions of axons remain widespread over the medial-lateral SC axis relative to the positioning of their terminal arborizations, and resemble the distributions labeled at E18-E19, with the exception that the small proportion of axons most widely mispositioned along the medial-lateral SC axis are less frequent. These data indicate that the most widely mispositioned retinal axons are preferentially eliminated, but that a high proportion of retinal axons mispositioned along the medial-lateral axis as they enter the SC can correct their position, form topographically appropriate arbors, and survive the remodeling period.
Assuntos
Envelhecimento/fisiologia , Axônios/ultraestrutura , Retina/anatomia & histologia , Colículos Superiores/anatomia & histologia , Animais , Transporte Axonal , Axônios/fisiologia , Carbocianinas , Corantes Fluorescentes , Idade Gestacional , Ratos , Ratos Sprague-Dawley , Retina/embriologia , Retina/crescimento & desenvolvimento , Colículos Superiores/embriologia , Colículos Superiores/crescimento & desenvolvimentoRESUMO
Though effective symptomatic therapies for Parkinson's disease exist, currently no treatment is proven to slow the progression of the underlying disease. Our growing understanding of the mechanisms of neuronal models, however, offers hope that neuroprotective strategies will soon be a standard part of the treatment of PD. Current approaches to the development of neuroprotective strategies are based on the hypothesized roles of oxidative stress and excitotoxicity in the degenerative process. In this article, we review evidence in support of these hypotheses as well as attempts to achieve neuroprotection in PD based on these and other mechanisms.
Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Animais , Agonistas de Dopamina/uso terapêutico , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Inibidores da Monoaminoxidase/uso terapêutico , Estresse Oxidativo , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Substância Negra/metabolismoRESUMO
Freezing of gait (FOG) and falls are major sources of disability for Parkinson's disease (PD) patients, and show limited responsiveness to medications. We assessed the efficacy of visual cues for overcoming FOG in an open-label study of 26 patients with PD. The change in the frequency of falls was a secondary outcome measure. Subjects underwent a 1-2 month baseline period of use of a cane or walker without visual cues, followed by 1 month using the same device with the laserlight visual cue. The laserlight visual cue was associated with a modest but significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 ± 0.48 (p = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was 39.5 ± 9.3% with the laserlight visual cue among subjects experiencing at least one fall during the baseline and subsequent study periods (p = 0.002; two-tailed one-sample t-test with hypothesized mean of 0). Though some individual subjects may have benefited, the overall mean performance on the timed gait test (TGT) across all subjects did not significantly change. However, among the 4 subjects who underwent repeated testing of the TGT, one showed a 50% mean improvement in TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t-test). This open-label study provides evidence for modest efficacy of a laserlight visual cue in overcoming FOG and reducing falls in PD patients.
Assuntos
Sinais (Psicologia) , Transtornos Neurológicos da Marcha/reabilitação , Lasers , Doença de Parkinson/reabilitação , Estimulação Luminosa/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Luz , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicaçõesRESUMO
OBJECTIVE: We investigated mitochondrial DNA (mtDNA) variants in children with a first episode of acquired demyelinating syndromes (PD-ADS) of the CNS and their relationship to disease phenotype, including subsequent diagnosis of multiple sclerosis (MS). METHODS: This exploratory analysis included the initial 213 children with PD-ADS in the prospective Canadian Pediatric Demyelinating Study and 166 matched healthy sibling controls from the Canadian Autism Genome Project. A total of 31 single nucleotide polymorphisms (SNPs) were analyzed, including haplogroup-defining SNPs and mtDNA variants previously reported to be associated with MS. RESULTS: Primary Leber hereditary optic neuropathy (LHON) mutations and other known pathogenic mtDNA mutations were absent in both patients with pediatric acquired demyelinating syndromes and controls. The 13708A haplogroup J-associated variant, previously linked to adult MS, was more frequent among subjects with PD-ADS (13.0%) compared to controls (6.2%; odds ratio [OR] 2.27; 95% confidence interval [CI] 1.06 to 4.83) and haplogroup M was associated with an earlier age at onset of PD-ADS (-1.74 years; 95% CI -3.33 to -0.07). In contrast, the haplogroup cluster UKJT, as well as 3 other SNPs, were each associated with a lower risk of PD-ADS. A total of 33 subjects with PD-ADS were diagnosed with MS during a mean follow-up period of 3.11 ± 1.14 (SD) years. No single SNP was associated with the risk of subsequent diagnosis of MS. However, haplogroup H was associated with an increased risk of MS (OR 2.60; 95% CI 1.21 to 5.55). CONCLUSION: These data suggest an association between mtDNA variants and the risk of PD-ADS and of a subsequent MS diagnosis. Replication of these findings in an independent population of subjects with PD-ADS is required.
Assuntos
DNA Mitocondrial/genética , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/genética , Variação Genética/genética , Haplótipos/genética , Mutação/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Adulto JovemAssuntos
Catarata/genética , DNA Mitocondrial/genética , Distonia/genética , NADH NADPH Oxirredutases/genética , Sequência de Bases , Western Blotting , Catarata/patologia , Análise Mutacional de DNA , DNA Mitocondrial/química , Distonia/patologia , Saúde da Família , Feminino , Mutação da Fase de Leitura , Humanos , Masculino , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , NADH NADPH Oxirredutases/metabolismo , LinhagemRESUMO
BACKGROUND: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects. OBJECTIVE: To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1. METHODS: With high-resolution melting, all 3 THAP1 exons were screened for sequence variants in 1,114 subjects with mainly adult-onset primary dystonia, 96 with unclassified dystonia, and 600 controls (400 neurologically normal and 200 with Parkinson disease). In addition, all 3 THAP1 exons were sequenced in 200 subjects with dystonia and 200 neurologically normal controls. RESULTS: Nine unique melting curves were found in 19 subjects from 16 families with primary dystonia and 1 control. Age at dystonia onset ranged from 8 to 69 years (mean 48 years). Sequencing identified 6 novel missense mutations in conserved regions of THAP1 (G9C [cervical, masticatory, arm], D17G [cervical], F132S [laryngeal], I149T [cervical and generalized], A166T [laryngeal], and Q187K [cervical]). One subject with blepharospasm and another with laryngeal dystonia harbored a c.-42C>T variant. A c.57C>T silent variant was found in 1 subject with segmental craniocervical dystonia. An intron 1 variant (c.71+9C>A) was present in 7 subjects with dystonia (7/1,210) but only 1 control (1/600). CONCLUSIONS: A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Proteínas de Ligação a DNA/genética , Distúrbios Distônicos/genética , Variação Genética/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação de Sentido Incorreto/genética , Linhagem , Adulto JovemRESUMO
A systematic review and meta-analysis were conducted to quantify the efficacy of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) for the treatment of motor dysfunction in patients with Parkinson's disease (PD). Prospective studies which evaluated the effects of either TMS (12 studies) or ECT (five studies) on motor function in PD using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) for TMS studies and any continuous measures of motor function in PD for ECT studies were included. The pooled effect size (standardised mean difference between pre-treatment versus post-treatment means) from a random effects model was 0.62 (95% confidence interval: 0.38, 0.85) for TMS treatment and 1.68 (0.79, 2.56) for ECT treatment, and from a fixed effects model was 0.59 (0.39, 0.78) for TMS treatment and 1.55 (1.07, 2.03) for ECT treatment. TMS, across applied stimulation sites and parameters, can exert a significant, albeit modest, positive effect on the motor function of patients with PD. ECT also may exert a significant effect on motor function in PD patients.
Assuntos
Eletroconvulsoterapia , Doença de Parkinson/terapia , Humanos , Transtornos das Habilidades Motoras/etiologia , Transtornos das Habilidades Motoras/terapia , Radiação , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Virtually all cells in humans depend on mitochondrial oxidative phosphorylation to generate energy, accounting for the remarkable diversity of clinical disorders associated with mitochondrial DNA mutations. However, certain tissues are particularly susceptible to mitochondrial dysfunction, resulting in recognizable clinical syndromes. Mitochondrial DNA mutations have been linked to seizures, strokes, optic atrophy, neuropathy, myopathy, cardiomyopathy, sensorineural hearing loss, diabetes mellitus, and other clinical features. Mitochondrial DNA mutations also may play an important role in aging, as well as in common age-related neurodegenerative disorders such as Parkinson's disease. Therefore, it is becoming increasingly important for clinicians to recognize the clinical syndromes suggestive of a mitochondrial disorder, and to understand the unique features of mitochondrial genetics that complicate diagnosis and genetic counseling.
Assuntos
Mitocôndrias/metabolismo , Envelhecimento/genética , Cardiomiopatias/genética , Transtornos Cerebrovasculares/genética , DNA Mitocondrial/genética , Diabetes Mellitus/genética , Aconselhamento Genético , Técnicas Genéticas , Perda Auditiva Neurossensorial/genética , Humanos , Mitocôndrias/genética , Encefalomiopatias Mitocondriais/genética , Miopatias Mitocondriais/genética , Mutação/genética , Doenças Neurodegenerativas/genética , Atrofias Ópticas Hereditárias/genética , Fosforilação Oxidativa , Doença de Parkinson/genética , Convulsões/genéticaRESUMO
We have studied in rats the topographic targeting of retinocollicular axons anterogradely labeled by focal retinal injections of the axon tracer DiI. We find that developing retinal axons widely mistarget along both the medial-lateral and the rostral-caudal axes of the superior colliculus (SC). In neonatal rats, labeled axons originating from injection sites in the temporal periphery covering less than 1% of the retina grow over most of the contralateral SC, suggesting that the growth cones of many axons initially fail to recognize their appropriate target region at the rostral SC border. Some of these axons correct their targeting errors and are retained; most do not and are eliminated. In neonates, peripheral nasal axons transiently develop branches throughout the SC. Branches formed by nasal axons are later restricted to a discrete terminal zone at the topographically appropriate, caudal SC border. At the neonatal stage, injections in temporal or nasal retina do result in a zone of increased labeling in the topographically correct region of the SC, but this zone is considerably larger than that labeled by a similar injection at a later stage. Thus, although the early projection is very diffuse, there is some bias for the correct region of the SC. Our findings indicate that in rats, developing retinal axons show only a limited specificity in their topographic targeting and branching. We conclude that mechanisms in addition to directed axon growth are required to establish the order characteristic of mature mammalian retinal projections.
Assuntos
Axônios/fisiologia , Nervo Óptico/crescimento & desenvolvimento , Retina/crescimento & desenvolvimento , Colículos Superiores/crescimento & desenvolvimento , Envelhecimento , Animais , Transporte Axonal , Carbocianinas , Corantes Fluorescentes , Lateralidade Funcional , Nervo Óptico/anatomia & histologia , Nervo Óptico/fisiologia , Ratos , Retina/anatomia & histologia , Retina/fisiologia , Colículos Superiores/anatomia & histologia , Colículos Superiores/fisiologia , Vias Visuais/anatomia & histologia , Vias Visuais/crescimento & desenvolvimentoRESUMO
We have used the anterograde axon tracer 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) to characterize the development of topographic order in the rat retinocollicular projection. Retinal axons were labeled by Dil injections covering 0.15-2% of peripheral temporal, nasal, superior, or inferior retina, or more central retina, in rats ranging in age from embryonic day 20 to postnatal day (P) 19. At P11-P12 and later, such injections label retinal axons that form overlapping arbors restricted to a topographically correct terminal zone covering about 1% of the superior colliculus (SC) area. At perinatal ages, though, axons labeled from each retinal site are distributed in the SC over much of its medial-lateral axis and extend caudally well beyond the rostral-caudal location of their correct terminal zone; some continue caudally into the inferior colliculus. Axons typically form side branches and often arborize at topographically incorrect positions throughout the SC; however, they appear to branch preferentially in a region that includes, but is much larger than, their correct terminal zone. The mature, retinotopically ordered projection emerges during an early postnatal remodeling period through the rapid remodeling of the early, diffuse projection. This process involves the large-scale removal of axons, axon segments, branches, and arbors from topographically inappropriate positions concurrently with a dramatic increase in branching and arborization at topographically correct locations. Quantitative measurements show that elimination of aberrant branches without loss of the primary axons contributes substantially to the development of order. By P6, fewer mistargeted axons persist, but those that do persist tend to branch or arborize more extensively in topographically inappropriate regions. By P8, the labeling patterns begin to approximate those seen at maturity. Further refinement leads to an adultlike topographic ordering of axonal arborizations by P11-P12. At maturity, some axons take very indirect routes to reach their correct terminal zone. However, such trajectory changes typically correct only small positional inaccuracies, indicating that axons and axon segments that make larger targeting errors do not survive the remodeling phase. Previous retrograde labeling studies indicate that some retinal axons make topographic targeting errors (O'Leary et al., 1986; Yhip and Kirby, 1990), but none have suggested the degree of diffuseness revealed by anterograde labeling with Dil. Our findings show that directed axon growth is inadequate as a mechanism to develop the topographic ordering of retinal axons in the rat SC. Rather, mechanisms that control the removal of mistargeted axons and promote the arborization of correctly positioned axons are critical for the development of retinotopic order.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Colículos Inferiores/fisiologia , Retina/fisiologia , Colículos Superiores/fisiologia , Transmissão Sináptica , Animais , Axônios/fisiologia , Mapeamento Encefálico , Carbocianinas , Corantes Fluorescentes , Cavidade Nasal/inervação , Plasticidade Neuronal , Ratos , Ratos Endogâmicos , Retina/ultraestrutura , Células Ganglionares da Retina/fisiologia , Células Ganglionares da Retina/ultraestruturaRESUMO
Explants from embryonic rat retina plated on Schwann cell monolayers were used to examine the mechanisms by which these central neurons interact with Schwann cell surfaces. Embryonic retinal explants extend neurites reliably on Schwann cell surfaces (Kleitman et al., 1988, J. Neurosci. 8: 653). Antibodies to molecules thought to be present on Schwann cell surfaces (laminin and the 217C antigen), on retinal neurite surfaces (Thy-1.1), or on both surfaces (L1) were tested for their ability to influence this neurite growth. Of these, only antibodies to L1 were effective in blocking retinal neurite extension on Schwann cells. Inhibition of neurite growth by anti-L1 was shown to be specific to growth on Schwann cell surfaces because neurite growth on air-dried collagen (a substratum known to support retinal neurite outgrowth) was not affected. This blockage was dose-dependent. At a low titer of anti-L1 Fab fragments defasciculation of neurites was prominent; at high titers 95% of neurite outgrowth was inhibited. This virtual elimination of the ability of Schwann cell surfaces to support embryonic retinal neurite growth in the presence of antibodies to L1 indicates that binding of the L1 molecule is a critical component of the mechanism by which Schwann cells foster the growth of these neurites. The present experiments concur with the growing body of evidence that L1 plays an important role in supporting neurite growth on cell surfaces and raise the possibility that L1 may also mediate the striking ability of adult retinal axons to regenerate in a peripheral nerve environment.