JNEN: Journal of Neuropathology & Experimental Neurology最新文献_第7页

Evidence for D‐Aspartyl‐β‐Amyloid Secretase Activity in Human Brain 人脑中D -天冬氨酸- β -淀粉样蛋白分泌酶活性的证据

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-02-01 DOI: 10.1093/JNEN/61.2.125

John M. Lee, L. Petrucelli, G. Fisher, Sona Ramdath, J. Castillo, M. M. Di Fiore, A. D’Aniello

引用次数: 12

Arrested Oligodendrocyte Lineage Progression During Human Cerebral White Matter Development: Dissociation Between the Timing of Progenitor Differentiation and Myelinogenesis 人类脑白质发育过程中少突胶质细胞谱系阻滞:祖细胞分化时间与髓鞘形成时间的分离

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-02-01 DOI: 10.1093/JNEN/61.2.197

S. Back, N. Luo, Natalia S. Borenstein, J. Volpe, H. Kinney

{"title":"Arrested Oligodendrocyte Lineage Progression During Human Cerebral White Matter Development: Dissociation Between the Timing of Progenitor Differentiation and Myelinogenesis","authors":"S. Back, N. Luo, Natalia S. Borenstein, J. Volpe, H. Kinney","doi":"10.1093/JNEN/61.2.197","DOIUrl":"https://doi.org/10.1093/JNEN/61.2.197","url":null,"abstract":"Immature oligodendrocytes (OLs) derive from a large pool of late OL progenitors that populate human cerebral white matter throughout the latter half of gestation. We recently reported that a minor population of immature OLs are present in human cerebral white matter for at least 3 months before these cells commit to myelinogenesis around 30 wk postconceptional age. Since this finding supports dissociation between the events that regulate human immature OL maturation and their commitment to myelinogenesis, we characterized here the cellular sequence of events that characterize immature OLs during the transition from a premyelinating to a myelinating state. Commitment of immature OLs to myelinogenesis in human cerebral white matter correlated with the longitudinal extension of specialized processes, designated “pioneer processes,” that made multiple types of apparent contacts with axons. This event coincided with the appearance of 3 distinct populations of sheaths that varied in their labeling for myelin basic protein (MBP). Since few axons initially labeled for MBP, this supported the occurrence in vivo of O4-negative, O1-positive premyelin sheaths that precede MBP-positive compacted myelin. These observations identify 3 sequential stages of early myelinogenesis: 1) the initial ensheathment of axons by premyelin sheaths generated by immature OLs; 2) the initial insertion of MBP into transitional sheaths; and 3) the generation of MBP-rich mature myelin.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"55 1","pages":"197–211"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81417283","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: 178

Altered Tubulin and Neurofilament Expression and Impaired Axonal Growth in Diabetic Nerve Regeneration 糖尿病神经再生中微管蛋白和神经丝表达改变和轴突生长受损

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-02-01 DOI: 10.1093/JNEN/61.2.164

Gang Xu, C. Pierson, Y. Murakawa, A. Sima

{"title":"Altered Tubulin and Neurofilament Expression and Impaired Axonal Growth in Diabetic Nerve Regeneration","authors":"Gang Xu, C. Pierson, Y. Murakawa, A. Sima","doi":"10.1093/JNEN/61.2.164","DOIUrl":"https://doi.org/10.1093/JNEN/61.2.164","url":null,"abstract":"Cytoskeletal protein expression in sensory neurons and sciatic nerve axonal growth were examined in type 1 diabetic BB/Wor rats after sciatic nerve crush injury. Diabetic male rats were subjected to sciatic nerve crush at 6 wk of diabetes. L4 and L5 dorsal root ganglia (DRG) mRNA expression of low and medium molecular weight neurofilaments (NF-L, NF-M), βII- and βIII-tubulin as well as protein expression of NF-L, NF-M, and β-tubulin were examined at various time points following crush injury and compared with age- and sex-matched non-diabetic BB/Wor rats. Steady state mRNA expression of NF-L, NF-M, βII- and βIII-tubulin were decreased in diabetic DRG. NF-L and NF-M proteins were also decreased in DRG of uncrushed diabetic animals. After crush injury, βII- and βIII-tubulin mRNA were upregulated in control animals at day 2 and day 6, respectively, and β-tubulin protein showed similarly increased expression after crush injury, while such upregulations did not occur in diabetic animals. Conversely, mRNA and protein expressions of NF-L, NF-M were downregulated to a lesser extent in diabetic animals compared to control rats. These changes were associated with impaired axonal elongation and caliber growth of regenerating fibers in diabetic rats. We propose that upregulation of tubulin has a negative feedback on NF expression in response to nerve injury, as seen in control rats. The absence of this upregulation in diabetic animals may impair its regulatory effect on NF expression and contribute to perturbed nerve regeneration seen in diabetic nerve.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"7 1","pages":"164–175"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78964782","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: 52

Evidence for Separable Functions of Tuberous Sclerosis Gene Products in Mammalian Cell Cycle Regulation 结节性硬化症基因产物在哺乳动物细胞周期调控中可分离功能的证据

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-02-01 DOI: 10.1093/JNEN/61.2.154

A. Miloloza, M. Kubista, M. Rosner, M. Hengstschläger

{"title":"Evidence for Separable Functions of Tuberous Sclerosis Gene Products in Mammalian Cell Cycle Regulation","authors":"A. Miloloza, M. Kubista, M. Rosner, M. Hengstschläger","doi":"10.1093/JNEN/61.2.154","DOIUrl":"https://doi.org/10.1093/JNEN/61.2.154","url":null,"abstract":"Tuberous sclerosis is an autosomal dominant disease affecting approximately 1 in 6,000 individuals. It is caused by mutations in either TSC1 on chromosome 9q34, which encodes hamartin, or TSC2 on chromosome 16p13.3, which encodes tuberin. The growths, named hamartomas, characteristically occur in different organs of patients and are speculated to result from defects in proliferation control. The observation that hamartin and tuberin can interact in vivo suggests that they might function in the same complex. Here we show that hamartin can affect proliferation control independent of the presence of functional tuberin and that binding to hamartin is not essential for tuberin to affect proliferation. Ectopic expression of hamartin negatively regulates proliferation to a similar extent in tuberin-positive and tuberin-negative cells; this is accompanied by binding to tuberin and upregulation of endogenous p27 in tuberin-positive cells and is without effects on p27 expression in the latter. Our data show for the first time that TSC proteins possess separable functions. We further demonstrate that hamartin can deregulate proliferation control by different mechanisms depending on the presence of tuberin. Besides an overlap in many features of patients with TSC1 and TSC2 mutations, data has accumulated that provides evidence for specific clinical differences. This study provides new insights into the cellular roles of TSC proteins and initiates a discussion of whether separable functions of these proteins might be associated with the clinical differences of TSC1- and TSC2-associated disease.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"77 1","pages":"154–163"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77912813","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: 26

Temporal Expression Pattern of Cerebrovascular Endothelial Cell Alkaline Phosphatase During Human Gestation 人妊娠期脑血管内皮细胞碱性磷酸酶的时间表达模式

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-01-01 DOI: 10.1093/JNEN/61.1.76

J. Anstrom, W. Brown, D. Moody, C. Thore, V. Challa, S. M. Block

{"title":"Temporal Expression Pattern of Cerebrovascular Endothelial Cell Alkaline Phosphatase During Human Gestation","authors":"J. Anstrom, W. Brown, D. Moody, C. Thore, V. Challa, S. M. Block","doi":"10.1093/JNEN/61.1.76","DOIUrl":"https://doi.org/10.1093/JNEN/61.1.76","url":null,"abstract":"In premature human neonates, immaturity of cerebral vessels can contribute to clinical problems such as germinal matrix hemorrhage and white matter damage. Afferent cerebral vessels in the brain of term babies express alkaline phosphatase (AP), an ectoenzyme located on the surface of endothelial cells. Using AP enzyme histochemistry we have examined the cerebrovasculature of premature live-born human neonates to determine when cerebral afferent vessels begin to express AP. Brains were collected at autopsy and processed for histological examination. AP-stained vessel density in the periventricular white matter was quantified using digital imaging and automated morphometry. Babies born prior to 28 wk gestation display few AP-positive vessels in the periventricular white matter, whereas, babies born after 28 wk gestation exhibit an AP-positive vascular pattern that resembles the adult pattern. In contrast, immunostaining for collagen revealed an extensive vascular network in both early and late gestation infants. Our measurements indicate that neonates born prior to 28 wk gestation are characterized by immature cerebral white matter afferent vessels and raise the possibility that the immaturity compromises vascular function.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"16 1","pages":"76–84"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88204865","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: 26

Accumulation of β‐Amyloid Precursor Protein in Axons Correlates with CNS Expression of SIV gp41 轴突β -淀粉样蛋白前体蛋白的积累与SIV gp41在中枢神经系统的表达相关

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-01-01 DOI: 10.1093/JNEN/61.1.85

J. Mankowski, S. Queen, P. Tarwater, Kelly Fox, V. Perry

{"title":"Accumulation of β‐Amyloid Precursor Protein in Axons Correlates with CNS Expression of SIV gp41","authors":"J. Mankowski, S. Queen, P. Tarwater, Kelly Fox, V. Perry","doi":"10.1093/JNEN/61.1.85","DOIUrl":"https://doi.org/10.1093/JNEN/61.1.85","url":null,"abstract":"Axonal damage represented by accumulation of β-amyloid precursor protein (β-APP) develops in numerous central nervous system (CNS) diseases including human immunodeficiency virus (HIV) infection. To study the underlying mechanisms of axonal damage associated with HIV CNS infection, the amount of axonal β-APP immunostaining in the corpus callosum of 24 simian immunodeficiency virus (SIV)-infected macaques and 3 control macaques was measured by computerized image analysis. The amounts of β-APP accumulation were then compared with time post-inoculation, extent and character of CNS inflammation, and viral load in the CNS measured by the amount of immunohistochemical staining for the viral transmembrane protein gp41. Significant increases over control values were present in 10 of 24 SIV-infected animals. SIV encephalitis was present in 9 of the 10 animals with elevated β-APP. Increases in β-APP correlated most strongly with levels of SIV gp41 in the brain (p = 0.005), but significant associations with macrophage infiltration and microglial activation (p = 0.04) and infiltration by cytotoxic lymphocytes (p = 0.05) also were identified. These data demonstrate that β-APP accumulation in the white matter of SIV-infected macaques develops during SIV infection in close correlation with levels of viral replication and may serve as a sensitive marker of neuronal/axonal damage mediated by viral proteins.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"4 1","pages":"85–90"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89190816","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: 67

Neuronal Migration, Cerebral Cortical Development, and Cerebral Cortical Anomalies 神经元迁移，大脑皮层发育和大脑皮层异常

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-01-01 DOI: 10.1093/JNEN/61.1.1

D. Pilz, N. Stoodley, J. Golden

引用次数: 111

Axon Loss in the Spinal Cord Determines Permanent Neurological Disability in an Animal Model of Multiple Sclerosis 多发性硬化症动物模型中脊髓轴突缺失决定永久性神经功能障碍

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-01-01 DOI: 10.1093/JNEN/61.1.23

J. Wujek, C. Bjartmar, E. Richer, R. Ransohoff, Min Yu, V. Tuohy, B. Trapp

{"title":"Axon Loss in the Spinal Cord Determines Permanent Neurological Disability in an Animal Model of Multiple Sclerosis","authors":"J. Wujek, C. Bjartmar, E. Richer, R. Ransohoff, Min Yu, V. Tuohy, B. Trapp","doi":"10.1093/JNEN/61.1.23","DOIUrl":"https://doi.org/10.1093/JNEN/61.1.23","url":null,"abstract":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Most patients undergo an initial relapsing-remitting (RR-MS) course that transforms into a relentless neurodegenerative disorder, termed secondary progressive (SP)-MS. Reversible inflammation and demyelination account readily for the pattern of RR-MS but provide an unsatisfactory explanation for irrevocable decline in SP-MS. Axon loss is thought to be responsible for progressive, non-remitting neurological disability during SP-MS. There is considerable potential for neuroprotective therapies in MS, but their application awaits animal models in which axonal loss correlates with permanent neurological disability. In this report, we describe quantitative immunohistochemical methods that correlate inflammation and axonal loss with neurological disability in chronic-relapsing experimental autoimmune encephalomyelitis (EAE). At first attack, CNS inflammation, but not axon loss, correlated with the degree of neurological disability. In contrast, fixed neurological impairment in chronic EAE correlated with axon loss that, in turn, correlated with the number of symptomatic attacks. As proposed for MS, these observations imply a causal relationship between inflammation, axon loss, and irreversible neurological disability. This chronic-relapsing EAE model provides an excellent platform for 2 critical objectives: investigating mechanisms of axon loss and evaluating efficacy of neuroprotective therapies.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"98 1","pages":"23–32"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74989030","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: 275

Morphological and Biochemical Correlations of Abnormal Tau Filaments in Progressive Supranuclear Palsy 进行性核上性麻痹中Tau蛋白丝异常的形态学和生化相关性

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-01-01 DOI: 10.1093/JNEN/61.1.33

Makio Takahashi, K. Weidenheim, D. Dickson, H. Ksiȩżak-Reding

{"title":"Morphological and Biochemical Correlations of Abnormal Tau Filaments in Progressive Supranuclear Palsy","authors":"Makio Takahashi, K. Weidenheim, D. Dickson, H. Ksiȩżak-Reding","doi":"10.1093/JNEN/61.1.33","DOIUrl":"https://doi.org/10.1093/JNEN/61.1.33","url":null,"abstract":"Progressive supranuclear palsy (PSP) is characterized by specific filamentous tau inclusions present in 3 types of cells including oligodendrocytes (coiled bodies), astrocytes (tufted astrocytes), and neurons (neurofibrillary tangles; NFTs). To correlate the morphological features and biochemical composition of tau in the inclusions, we examined tau filament-enriched fractions isolated from selected brain regions. Frontal and cerebellar white matter manifested a predominance of coiled bodies. The isolated fractions contained straight, 14-nm-wide filaments of relatively smooth appearance. Caudate nucleus and motor cortex with numerous tufted astrocytes contained mostly straight, but irregular, 22-nm-wide filaments with jagged contours. Perirhinal cortex and hippocampus, rich in NFTs, contained 22-nm-wide filaments that were twisted at 80-nm intervals. Among the regions, those with tufted astrocytes showed the most heterogeneity in the ultrastructure of filaments. In all regions, isolated filaments were immunolabeled with PHF-1, Tau 46, and AT8. Fractions from all regions showed 2 PHF-1 immunoreactive bands of 64 and 68 kDa, while an additional band of 60 kDa was detected in NFT-enriched regions. All fractions, in varying extents, showed Tau-1-immunoreactive bands between 45–64 kDa. The results indicate that the 3 types of PSP tau inclusions vary in the ultrastructure although with some overlapping features. Neuronal and glial inclusions also vary in the biochemical profile of tau protein. These differences may depend on the metabolism of tau in the diseased oligodendrocytes, astrocytes, and neurons.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"1 1","pages":"33–45"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75851408","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

Endoplasmic Reticulum Stress in PLP‐Overexpressing Transgenic Rats: Gray Matter Oligodendrocytes Are More Vulnerable than White Matter Oligodendrocytes 过表达PLP转基因大鼠的内质网应激:灰质少突胶质细胞比白质少突胶质细胞更脆弱

JNEN: Journal of Neuropathology & Experimental Neurology Pub Date : 2002-01-01 DOI: 10.1093/JNEN/61.1.12

J. Bauer, M. Bradl, M. Klein, M. Leisser, T. Deckwerth, H. Wekerle, H. Lassmann

{"title":"Endoplasmic Reticulum Stress in PLP‐Overexpressing Transgenic Rats: Gray Matter Oligodendrocytes Are More Vulnerable than White Matter Oligodendrocytes","authors":"J. Bauer, M. Bradl, M. Klein, M. Leisser, T. Deckwerth, H. Wekerle, H. Lassmann","doi":"10.1093/JNEN/61.1.12","DOIUrl":"https://doi.org/10.1093/JNEN/61.1.12","url":null,"abstract":"Studies dealing with transport of proteins from the oligodendrocyte cell body to the myelin sheath reveal the presence of different transport pathways. Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER) and then processed through the Golgi apparatus and transported to the myelin membranes. Myelin basic protein (MBP) on the other hand is synthesized locally at the ends of cell processes where its messenger RNA is translated on free ribosomes. Here we show that in rats that overexpress PLP, impairment of PLP transport from the cell body to the processes interferes with the translocation of other membrane proteins such as myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG), but not with peripherally translated MBP. In addition, it also impedes the transport of non-myelin proteins, for example the amyloid precursor protein (APP). At the ultrastructural level, the ER of these metabolically disturbed oligodendrocytes revealed extreme swelling of the cisternae, and immunohistochemistry revealed intense expression of the ER chaperone molecule BiP/GRP78 and ER folding enzyme protein disulfide isomerase (PDI). These features suggest that these oligodendrocytes, which were found exclusively in gray matter areas of the spinal cord, started an unfolded protein response while suffering from ER stress. Some of these disturbed oligodendrocytes were seen to undergo programmed cell death. These results indicate that gray matter oligodendrocyte differ from white matter oligodendrocytes in their capacity to stabilize metabolic disturbances by an unfolded protein response.","PeriodicalId":14858,"journal":{"name":"JNEN: Journal of Neuropathology & Experimental Neurology","volume":"68 1","pages":"12–22"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90877914","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: 76