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Antiandrogen blocks estrogen-induced masculinization of the song system in female zebra finches. 抗雄激素阻断雌性斑胸草雀鸣叫系统中雌激素诱导的雄性化。
Journal of neurobiology Pub Date : 2002-04-01 DOI: 10.1002/NEU.10028
W. Grisham, Janet Lee, Mary Ellen McCormick, Kay Yang-Stayner, A. Arnold
{"title":"Antiandrogen blocks estrogen-induced masculinization of the song system in female zebra finches.","authors":"W. Grisham, Janet Lee, Mary Ellen McCormick, Kay Yang-Stayner, A. Arnold","doi":"10.1002/NEU.10028","DOIUrl":"https://doi.org/10.1002/NEU.10028","url":null,"abstract":"Song behavior and the neural song system that serves it are sexually dimorphic in zebra finches. In this species, males sing and females normally do not. The sex differences in the song system include sex differences in the proportion of neurons that express androgen receptors, which is higher in specific brain regions of males. Estradiol (E2) administered in early development profoundly masculinizes the song system of females, including the proportion of neurons expressing androgen receptors. We examined whether or not the expression of these androgen receptors was causally related to the E2-induced masculinization of this system by co-administering Flutamide, which blocks androgen action at the receptor, along with E2 at hatching. E2 alone had its usual masculinizing effect on the female song system, measured in adulthood: increasing the size of song nuclei, the size of neurons in HVC, RA, and 1MAN, and the number of neurons in HVC. E2's masculinizing action, however, was significantly diminished on all measures by co-administering Flutamide. Indeed, females receiving both E2 and Flutamide were never significantly more masculine than controls on any measure. Flutamide alone had no effect. Our results strongly suggest that the activation of androgen receptors is necessary for the E2-induced masculinization of the song system in females.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"26 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2002-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81280255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 33
Novel UNC-44 AO13 ankyrin is required for axonal guidance in C. elegans, contains six highly repetitive STEP blocks separated by seven potential transmembrane domains, and is localized to neuronal processes and the periphery of neural cell bodies. 新的UNC-44 AO13锚蛋白是秀丽隐杆线虫轴突引导所必需的,包含6个高度重复的STEP块,由7个潜在的跨膜结构域分开,并且定位于神经元过程和神经细胞体的外围。
Journal of neurobiology Pub Date : 2002-03-01 DOI: 10.1002/NEU.10036
A. Otsuka, P. Boontrakulpoontawee, N. Rebeiz, M. Domanus, Dawn Otsuka, N. Velamparampil, Sabrina Chan, Marshall Vande Wyngaerde, S. Campagna, Andrea Cox
{"title":"Novel UNC-44 AO13 ankyrin is required for axonal guidance in C. elegans, contains six highly repetitive STEP blocks separated by seven potential transmembrane domains, and is localized to neuronal processes and the periphery of neural cell bodies.","authors":"A. Otsuka, P. Boontrakulpoontawee, N. Rebeiz, M. Domanus, Dawn Otsuka, N. Velamparampil, Sabrina Chan, Marshall Vande Wyngaerde, S. Campagna, Andrea Cox","doi":"10.1002/NEU.10036","DOIUrl":"https://doi.org/10.1002/NEU.10036","url":null,"abstract":"Conventional ankyrins are cortical cytoskeletal proteins that form an ankyrin-spectrin meshwork underlying the plasma membrane. We report here the unusual structure of a novel ankyrin (AO13 ankyrin, 775,369 Da, 6994 aa, pI = 4.45) that is required for proper axonal guidance in Caenorhabditis elegans. AO13 ankyrin contains the ANK repeat and spectrin-binding domains found in other ankyrins, but differs from all others in that the acidic carboxyl region contains six blocks of serine/threonine/glutamic acid/proline rich (STEP) repeats separated by seven hydrophobic domains. The STEP repeat blocks are composed primarily of sequences related to ETTTTTTVTREHFEPED(E/D)X(n)VVESEEYSASGSPVPSE (E/K)DVE(H/R)VI, and the hydrophobic domains contain sequences related to PESGEESDGEGFGSKVLGFAKK[AGMVAGGVVAAPVALAAVGA]KAAYDALKKDDDEE, which includes a potential transmembrane domain (in brackets). Recombinant protein fragments of AO13 ankyrin were used to prepare polyclonal antisera against the spectrin-binding domain (AO271 Ab), the conventional ankyrin regulatory domain (AO280 Ab), the AO13 ankyrin STEP domain (AO346 Ab), the AO13 ankyrin STEP + hydrophobic domain (AO289 Ab), and against two carboxyl terminal domain fragments (AO263 Ab and AO327 Ab). Western blot analysis with these Ab probes demonstrated multiple protein isoforms. By immunofluorescence microscopy, the antispectrin-binding and regulatory domain (AO271 and AO280) antibodies recognized many cell types, including neurons, and stained the junctions between cells. The AO13 ankyrin-specific (AO289 and AO346) antibodies showed a neurally restricted pattern, staining nerve processes and the periphery of neural cell bodies. These results are consistent with a role for AO13 ankyrin in neural development.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"12 1","pages":"333-49"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73781253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Neural progenitor cells of the neonatal rat anterior subventricular zone express functional GABA(A) receptors. 新生大鼠脑室前下区神经祖细胞表达功能性GABA受体。
Journal of neurobiology Pub Date : 2002-03-01 DOI: 10.1002/NEU.10038
Randall R. Stewart, G. Hoge, T. Zigova, M. Luskin
{"title":"Neural progenitor cells of the neonatal rat anterior subventricular zone express functional GABA(A) receptors.","authors":"Randall R. Stewart, G. Hoge, T. Zigova, M. Luskin","doi":"10.1002/NEU.10038","DOIUrl":"https://doi.org/10.1002/NEU.10038","url":null,"abstract":"The interneurons of the olfactory bulb arise from precursor cells in the anterior part of the neonatal subventricular zone, the SVZa, and are distinctive in that they possess a neuronal phenotype and yet undergo cell division. To characterize the differentiation of neonatal SVZa progenitor cells, we analyzed the complement of ionotropic neurotransmitter receptors that they express in vitro. For this analysis, we tested the sensitivity of SVZa progenitor cells to gamma-amino-n-butyric acid (GABA), adenosine triphosphate (ATP), kainate, N-methyl-D-aspartate (NMDA), and acetylcholine (ACh) after 1 day in vitro. SVZa progenitor cells had chloride currents activated by GABA and muscimol, the GABA(A) receptor-specific agonist, but were insensitive to ATP, kainate, NMDA, and ACh. In addition, GABA- or muscimol-activated chloride currents were blocked nearly completely by 30 microM bicuculline, the GABA(A) receptor-specific antagonist, suggesting that GABA(B) and GABA(C) receptors are absent. Measurements of the chloride reversal potential by gramicidin-perforated patch clamp revealed that currents generated by activation of GABA(A) receptors were inward, and thus, depolarizing. A set of complementary experiments was undertaken to determine by reverse transcription and polymerase chain reaction (RT-PCR) whether SVZa progenitor cells express the messenger RNA (mRNA) coding for glutamic acid decarboxylase 67 (GAD67), used in the synthesis of GABA and for GABA(A) receptor subunits. Both postnatal day (P0) SVZa and olfactory bulb possessed detectable mRNA coding for GAD67. In P0 SVZa, the GABA(A) receptor subunits detected with RT-PCR included alpha 2-4, beta 1-3, and gamma 2S (short form). By comparison, the P0 olfactory bulb expressed all of the subunits detectable in the SVZa and additional subunit mRNAs: alpha 1, alpha 5, gamma 1, gamma 2L (long form), gamma 3, and delta subunit mRNAs. Antibodies recognizing GABA, GAD, and various GABA(A) receptor subunits were used to label SVZa cells harvested from P0-1 rats and cultured for 1 day. The cells were immunoreactive for GABA, GAD, and the GABA(A) receptor subunits alpha 2-5, beta 1-3, and gamma 2. To relate the characteristics of GABA(A) receptors in cultured SVZa precursor cells to particular combinations of subunits, the open reading frames of the dominant subunits detected by RT-PCR (alpha 2-4, beta 3, and gamma 2S) were cloned into a mammalian cell expression vector and different combinations were transfected into Chinese hamster ovary-K1 (CHO-K1) cells. A comparison of the sensitivity to inhibition by zinc of GABA(A) receptors in SVZa precursor cells and in CHO-K1 cells expressing various combinations of recombinant GABA(A) receptor subunits suggested that the gamma 2S subunit was present and functional in the GABA(A) receptor chloride channel complex. Thus, SVZa precursor cells are GABAergic and a subset of the GABA(A) receptor subunits detected in the olfactory bulb was found in the SVZa, as might be","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"17 1","pages":"305-22"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88318363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 104
Local calcium changes regulate the length of growth cone filopodia. 局部钙的变化调节生长锥丝状足的长度。
Journal of neurobiology Pub Date : 2002-03-01 DOI: 10.1002/NEU.10027
Su Cheng, Matthew S. Geddis, V. Rehder
{"title":"Local calcium changes regulate the length of growth cone filopodia.","authors":"Su Cheng, Matthew S. Geddis, V. Rehder","doi":"10.1002/NEU.10027","DOIUrl":"https://doi.org/10.1002/NEU.10027","url":null,"abstract":"Previous studies have demonstrated that the free intracellular calcium concentration ([Ca(2+)](i)) in growth cones can act as an important regulator of growth cone behavior. Here we investigated whether there is a spatial and temporal correlation between [Ca(2+)](i) and one particular aspect of growth cone behavior, namely the regulation of growth cone filopodia. Calcium was released from the caged compound NP-EGTA (o-nitrophenyl EGTA tetrapotassium salt) to simulate a signaling event in the form of a transient increase in [Ca(2+)](i). In three different experimental paradigms, we released calcium either globally (within an entire growth cone), regionally (within a small area of the lamellipodium), or locally (within a single filopodium). We demonstrate that global photolysis of NP-EGTA in growth cones caused a transient increase in [Ca(2+)](i) throughout the growth cone and elicited subsequent filopodial elongation that was restricted to the stimulated growth cone. Pharmacological blockage of either calmodulin or the Ca(2+)-dependent phosphatase, calcineurin, inhibited the effect of uncaging calcium, suggesting that these enzymes are acting downstream of calcium. Regional uncaging of calcium in the lamellipodium caused a regional increase in [Ca(2+)](i), but induced filopodial elongation on the entire growth cone. Elevation of [Ca(2+)](i) locally within an individual filopodium resulted in the elongation of only the stimulated filopodium. These findings suggest that the effect of an elevation of [Ca(2+)](i) on filopodial behavior depends on the spatial distribution of the calcium signal. In particular, calcium signals within filopodia can cause filopodial length changes that are likely a first step towards directed filopodial steering events seen during pathfinding in vivo.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"78 5 Pt 1 1","pages":"263-75"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74588403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 42
BMP-2 and cAMP elevation confer locus coeruleus neurons responsiveness to multiple neurotrophic factors. BMP-2和cAMP升高赋予蓝斑神经元对多种神经营养因子的反应性。
Journal of neurobiology Pub Date : 2002-03-01 DOI: 10.1002/NEU.10034
J. Reiriz, Pontus C. Holm, J. Alberch, E. Arenas
{"title":"BMP-2 and cAMP elevation confer locus coeruleus neurons responsiveness to multiple neurotrophic factors.","authors":"J. Reiriz, Pontus C. Holm, J. Alberch, E. Arenas","doi":"10.1002/NEU.10034","DOIUrl":"https://doi.org/10.1002/NEU.10034","url":null,"abstract":"The locus coeruleus (LC) is a major target of several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, very little is known of the trophic requirements of LC neurons. In the present work, we have studied the biological activity of neurotrophic factors from different families in E15 primary cultures of LC neurons. In agreement with previous results, neurotrophin-3 (NT-3) and also glial cell line- derived neurotrophic factor (GDNF) increased the number of embryonic LC noradrenergic neurons in the presence of serum. In serum-free conditions, none of the factors tested, including NT-3, GDNF, neurturin, basic fibroblast growth factor (bFGF), or bone morphogenetic protein-2 (BMP-2), promoted the survival of tyrosine hydroxylase (TH)-immunoreactive neurons at 6 days in vitro. However, when BMP-2 was coadministered with any of these factors the number of LC TH-positive neurons increased twofold. Similar results were obtained by cotreatment of LC neurons with forskolin and NT-3, bFGF, or BMP-2. The strongest effect (a fourfold increase in the number of TH-positive cells) was induced by cotreatment with forskolin, BMP-2, and GDNF. Thus, our results show that LC neurons require multiple factors for their survival and development, and suggest that activation of LC neurons by bone morphogenetic proteins and cAMP plays a decisive role in conferring noradrenergic neuron responsiveness to several trophic factors.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"15 1","pages":"291-304"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88154055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 27
Chronic alterations in serotonin function: dynamic neurochemical properties in agonistic behavior of the crayfish, Orconectes rusticus. 5 -羟色胺功能的慢性改变:小龙虾激动行为的动态神经化学特性。
Journal of neurobiology Pub Date : 2002-03-01 DOI: 10.1002/NEU.10035
J. B. Panksepp, R. Huber
{"title":"Chronic alterations in serotonin function: dynamic neurochemical properties in agonistic behavior of the crayfish, Orconectes rusticus.","authors":"J. B. Panksepp, R. Huber","doi":"10.1002/NEU.10035","DOIUrl":"https://doi.org/10.1002/NEU.10035","url":null,"abstract":"The biogenic amine serotonin [5-hydroxytryptamine (5-HT)] has received considerable attention for its role in behavioral phenomena throughout a broad range of invertebrate and vertebrate taxa. Acute 5-HT infusion decreases the likelihood of crayfish to retreat from dominant opponents. The present study reports the biochemical and behavioral effects resulting from chronic treatment with 5-HT-modifying compounds delivered for up to 5 weeks via silastic tube implants. High performance liquid chromatography with electrochemical detection (HPLC-ED) confirmed that 5,7-dihydroxytryptamine (5,7-DHT) effectively reduced 5-HT in all central nervous system (CNS) areas, except brain, while a concurrent accumulation of the compound was observed in all tissues analyzed. Unexpectedly, two different rates of chronic 5-HT treatment did not increase levels of the amine in the CNS. Behaviorally, 5,7-DHT treated crayfish exhibited no significant differences in measures of aggression. Although treatment with 5-HT did not elevate 5-HT content in the CNS, infusion at a slow rate caused animals to escalate more quickly while 5-HT treatment at a faster rate resulted in slower escalation. 5,7-DHT is commonly used in behavioral pharmacology and the present findings suggest its biochemical properties should be more thoroughly examined. Moreover, the apparent presence of powerful compensatory mechanisms indicates our need to adopt an increasingly dynamic view of the serotonergic bases of behavior like crayfish aggression.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"28 1","pages":"276-90"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85434515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 51
Striatopallidal neurons are selectively protected by neurturin in an excitotoxic model of Huntington's disease. 在亨廷顿氏病的兴奋性毒性模型中,纹状突起神经元被神经蛋白选择性地保护。
Journal of neurobiology Pub Date : 2002-03-01 DOI: 10.1002/NEU.10033
S. Marco, E. Pérez-Navarro, E. Tolosa, E. Arenas, J. Alberch
{"title":"Striatopallidal neurons are selectively protected by neurturin in an excitotoxic model of Huntington's disease.","authors":"S. Marco, E. Pérez-Navarro, E. Tolosa, E. Arenas, J. Alberch","doi":"10.1002/NEU.10033","DOIUrl":"https://doi.org/10.1002/NEU.10033","url":null,"abstract":"Excitotoxicity has been involved in the pathogenesis of several neurodegenerative disorders. Using intrastriatal quinolinic acid (QUIN) injection as an animal model of Huntington's disease, we attempt to identify the neurotransmitter phenotype of striatal projection neurons protected by neurturin (NRTN). Control or NRTN-secreting cell lines were grafted in the striatum before QUIN injection and striatal projection neurons were examined by retrograde Fluorogold labeling and in situ hybridization. Intrastriatal grafting of NRTN-secreting cell line selectively prevented the loss of striatopallidal neurons and also the decrease in the mRNA levels for their markers (glutamic acid decarboxylase 67 and preproenkephalin) induced by QUIN, without affecting striatonigral neurons. Thus, our findings show that NRTN is a selective neuroprotective factor for striatopallidal neurons, suggesting that it might be a candidate for the treatment of movement disorders in which this neuronal population is affected.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"194 1","pages":"323-32"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83090551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Targeted expression of tetanus neurotoxin interferes with behavioral responses to sensory input in Drosophila. 破伤风神经毒素的靶向表达干扰果蝇对感觉输入的行为反应。
Journal of neurobiology Pub Date : 2002-02-15 DOI: 10.1002/NEU.10029
A. Keller, S. Sweeney, T. Zars, C. O’Kane, M. Heisenberg
{"title":"Targeted expression of tetanus neurotoxin interferes with behavioral responses to sensory input in Drosophila.","authors":"A. Keller, S. Sweeney, T. Zars, C. O’Kane, M. Heisenberg","doi":"10.1002/NEU.10029","DOIUrl":"https://doi.org/10.1002/NEU.10029","url":null,"abstract":"Targeted inactivation of neurons by expression of toxic gene products is a useful tool to assign behavioral functions to specific neurons or brain structures. Of a variety of toxic gene products tested, tetanus neurotoxin light chain (TNT) has the least severe side effects and can completely block chemical synapses. By using the GAL4 system to drive TNT expression in a subset of chemo- and mechanosensory neurons, we detected walking and flight defects consistent with blocking of relevant sensory information. We also found, for the first time, an olfactory behavioral phenotype associated with blocking of a specific subset of antennal chemoreceptors. Similar behavioral experiments with GAL4 lines expressing in different subsets of antennal chemoreceptors should contribute to an understanding of olfactory coding in Drosophila. To increase the utility of the GAL4 system for such purposes, we have designed an inducible system that allows us to circumvent lethality caused by TNT expression during early development.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"21 2 1","pages":"221-33"},"PeriodicalIF":0.0,"publicationDate":"2002-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86758733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 48
Muscle-derived neurotrophin-3 reduces injury-induced proprioceptive degeneration in neonatal mice. 肌源性神经营养因子-3减少新生小鼠损伤性本体感觉变性。
Journal of neurobiology Pub Date : 2002-02-15 DOI: 10.1002/NEU.10024
D. Wright, J. M. Williams, J. McDonald, Julie A. Carlsten, Michael D. Taylor
{"title":"Muscle-derived neurotrophin-3 reduces injury-induced proprioceptive degeneration in neonatal mice.","authors":"D. Wright, J. M. Williams, J. McDonald, Julie A. Carlsten, Michael D. Taylor","doi":"10.1002/NEU.10024","DOIUrl":"https://doi.org/10.1002/NEU.10024","url":null,"abstract":"During perinatal development, proprioceptive muscle afferents are quite sensitive to nerve injury. Here, we have used transgenic mice that overexpress neurotrophin-3 (NT-3) in skeletal muscle (myo/NT-3 mice) to explore whether NT-3 plays a neuroprotective role for perinatal muscle afferents following nerve injury. Measurements of NT-3 mRNA using RT-PCR revealed that levels of endogenous NT-3 mRNA in wild-type muscles remained constant during the first postnatal week following nerve crush or nerve section on postnatal day (PN) 1. In comparison, myo/NT-3 mice had significantly elevated levels of NT-3 mRNA that were maintained or increased following injury. To assess whether muscle-derived NT-3 could prevent injury-induced neuronal death, neuron survival in the DRG was analyzed in mice 5 days after sciatic nerve crush on PN3. Retrograde prelabeling of muscle afferents and parvalbumin immunocytochemistry both revealed that overexpression of NT-3 in muscle significantly reduced neuronal loss following injury. Similar neuroprotective effects of NT-3 were observed in wild-type mice injected with exogenous NT-3 in the gastrocnemius muscles. To test whether NT-3 could prevent muscle spindle degeneration, spindle number and morphology were assessed 3 weeks after sciatic nerve crush or section on PN1. No spindles were present in either wildtype or myo/NT-3 muscles after nerve section, demonstrating that NT-3 overexpression cannot maintain spindles following complete denervation. Moreover, NT-3 overexpression could not prevent moderate spindle loss in muscle and did not stimulate new spindle formation following nerve crush. Our results demonstrate that in addition to its early actions on sensory neuron generation and naturally occurring cell death, NT-3 has important neuroprotective effects on muscle afferents during postnatal development.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"89 7","pages":"198-208"},"PeriodicalIF":0.0,"publicationDate":"2002-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72567451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent. 损伤诱导的脊髓运动神经元凋亡发生在DNA单链断裂之前,并且依赖于p53和bax。
Journal of neurobiology Pub Date : 2002-02-15 DOI: 10.1002/NEU.10026
L. Martin, Zhiping Liu
{"title":"Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent.","authors":"L. Martin, Zhiping Liu","doi":"10.1002/NEU.10026","DOIUrl":"https://doi.org/10.1002/NEU.10026","url":null,"abstract":"The mechanisms of injury-induced apoptosis of neurons within the spinal cord are not understood. We used a model of peripheral nerve-spinal cord injury in the rat and mouse to induce motor neuron degeneration. In this animal model, unilateral avulsion of the sciatic nerve causes apoptosis of motor neurons. We tested the hypothesis that p53 and Bax regulate this neuronal apoptosis, and that DNA damage is an early upstream signal. Adult mice and rats received unilateral avulsions causing lumbar motor neurons to achieve endstage apoptosis at 7-14 days postlesion. This motor neuron apoptosis is blocked in bax(-/-) and p53(-/-) mice. Single-cell gel electrophoresis (comet assay), immunocytochemistry, and quantitative immunogold electron microscopy were used to measure molecular changes in motor neurons during the progression of apoptosis. Injured motor neurons accumulate single-strand breaks in DNA by 5 days. p53 accumulates in nuclei of motor neurons destined to undergo apoptosis. p53 is functionally activated by 4-5 days postlesion, as revealed by immunodetection of phosphorylated p53. Preapoptotically, Bax translocates to mitochondria, cytochrome c accumulates in the cytoplasm, and caspase-3 is activated. These results demonstrate that motor neuron apoptosis in the adult spinal cord is controlled by upstream mechanisms involving DNA damage and activation of p53 and downstream mechanisms involving upregulated Bax and cytochrome c and their translocation, accumulation of mitochondria, and activation of caspase-3. We conclude that adult motor neuron death after nerve avulsion is DNA damage-induced, p53- and Bax-dependent apoptosis.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"1 1","pages":"181-97"},"PeriodicalIF":0.0,"publicationDate":"2002-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72663950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 100
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