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25 February 2014, Volume 9 Issue 4 Previous Issue    Next Issue

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Neuronal growth cones and regeneration: gridlock within the extracellular matrix Snow DM 2014, 9 (4):  341-342.  doi: 10.4103/1673-5374.128234 Abstract ( 296 )   PDF (135KB) ( 839 )   Save Related Articles | Metrics

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Proteoglycans: Road Signs for Neurite Outgrowth Justin A. Beller, Diane M. Snow 2014, 9 (4):  343-355.  doi: 10.4103/1673-5374.128235 Abstract ( 245 )   PDF (1049KB) ( 1180 )   Save Proteoglycans in the central nervous system play integral roles as “traffic signals” for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the injured central nervous system. Related Articles | Metrics

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Traffic lights for axon growth: proteoglycans and their neuronal receptors Shen Y 2014, 9 (4):  356-361.  Abstract ( 248 )   PDF (201KB) ( 1067 )   Save 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 traffic lights in controlling the migrating axons, chondroitin sulfate proteoglycans (CSPGs) and heparan 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 identification of these proteoglycan receptors offered potential therapeutic targets for promoting post-injury axon regeneration. Related Articles | Metrics

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Time dependent integration of matrix metalloproteinases and their targeted substrates directs axonal sprouting and synaptogenesis following central nervous system injury Linda L. Phillips, Julie L. Chan, Adele E. Doperalski, Thomas M. Reeves 2014, 9 (4):  362-376.  doi: 10.4103/1673-5374.128237 Abstract ( 284 )   PDF (4043KB) ( 1150 )   Save Over the past two decades, many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity. The majority of these studies involve proteins which are targets of matrix metalloproteinases. Importantly, these enzyme/substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity, directing axonal and dendritic reorganization after brain insult. The present review first summarizes literature support for the prominent role of matrix metalloproteinases during neuroregeneration, followed by a discussion of data contrasting adaptive and maladaptive neuroplasticity that reveals time-dependent metalloproteinase/substrate regulation of postinjury synaptic recovery. The potential for these enzymes to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experiments demonstrating that metalloproteinase inhibitors can alter adaptive and maladaptive outcome. Finally, the complexity of metalloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzymes interact with immune molecules to mediate cellular response in the local regenerative environment, and are regulated by novel binding partners in the brain extracellular matrix. Together, these different examples show the complexity with which metalloproteinases are integrated into the process of neuroregeneration, and point to a promising new angle for future studies exploring how to facilitate brain plasticity. Related Articles | Metrics

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In the presence of danger: the extracellular matrix defensive response to central nervous system injury Lyn B. Jakeman, Kent E. Williams, Bryan Brautigam 2014, 9 (4):  377-384.  doi: 10.4103/1673-5374.128238 Abstract ( 316 )   PDF (1426KB) ( 975 )   Save Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient neurotransmission and axon potential propagation. In the normal adult CNS, the extracellular matrix (ECM) is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter     becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/central nervous system border. An advantage of this response is to limit the invasion of damaging   cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed. Related Articles | Metrics

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Regulatory effects of inhibiting the activation of glial cells on retinal synaptic plasticity Lihong Zhou, Hui Wang, Jia Luo, Kun Xiong, Leping Zeng, Dan Chen, Jufang Huang 2014, 9 (4):  385-393.  doi: 10.4103/1673-5374.128240 Abstract ( 312 )   PDF (1837KB) ( 1760 )   Save Various retinal injuries induced by ocular hypertension have been shown to induce plastic changes in retinal synapses, but the potential regulatory mechanism of synaptic plasticity after retinal injury was still unclear. A rat model of acute ocular hypertension was established by injecting saline intravitreally for an hour, and elevating the intraocular pressure to 14.63 kPa (110 mmHg). Western blot assay and immunofluorescence results showed that synaptophysin expression had a distinct spatiotemporal change that increased in the inner plexiform layer within 1 day and spread across the outer plexiform layer after 3 days. Glial fibrillary acidic protein expression in retinae was greatly increased after 3 days, and reached a peak at 7 days, which was also consistent with the peak time of synaptophysin expression in the outer plexiform layer following the increased intraocular pressure. Fluorocitrate, a glial metabolic inhibitor, was intravitreally injected to inhibit glial cell activation following high intraocular pressure. This significantly inhibited the enhanced glial fibrillary acidic protein expression induced by high intraocular pressure injury. Synaptophysin expression also decreased in the inner plexiform layer within a day and the widened distribution in the outer plexiform layer had disappeared by 3 days. The results suggested that retinal glial cell activation might play an important role in the process of retinal synaptic plasticity induced by acute high intraocular pressure through affecting the expression and distribution of synaptic functional proteins, such as synaptophysin. Related Articles | Metrics

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Characterization of hippocampal Cajal-Retzius cells during development in a mouse model of Alzheimer’s disease (Tg2576) Dongming Yu, Wenjuan Fan, Ping Wu, Jiexin Deng, Jing Liu, Yanli Niu, Mingshan Li, Jinbo Deng 2014, 9 (4):  394-401.  doi: 10.4103/1673-5374.128243 Abstract ( 264 )   PDF (1578KB) ( 1574 )   Save Cajal-Retzius cells are reelin-secreting neurons in the marginal zone of the neocortex and hippocampus. The aim of this study was to investigate Cajal-Retzius cells in Alzheimer’s disease pathology. Results revealed that the number of Cajal-Retzius cells markedly reduced with age in both wild type and in mice over-expressing the Swedish double mutant form of amyloid precursor protein 695 (transgenic (Tg) 2576 mice). Numerous reelin-positive neurons were positive for activated caspase 3 in Tg2576 mice, suggesting that Cajal-Retzius neuronal loss occurred via apoptosis in this Alzheimer’s disease model. Compared with wild type, the number of Cajal-Retzius cells was significantly lower in Tg2576 mice. Western blot analysis confirmed that reelin levels were markedly lower in Tg2576 mice than in wild-type mice. The decline in Cajal-Retzius cells in Tg2576 mice was found to occur concomitantly with the onset of Alzheimer’s disease amyloid pathology and related behavioral deficits. Overall, these data indicated that Cajal-Retzius cell loss occurred with the onset and development of Alzheimer’s disease. Related Articles | Metrics

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The Pael-R gene does not mediate the changes in rotenone-induced Parkinson’s disease model cells Ting Zou, Xiangqi Tang, Zhiling Huang, Niangui Xu, Zhiping Hu 2014, 9 (4):  402-406.  doi: 10.4103/1673-5374.128245 Abstract ( 189 )   PDF (535KB) ( 1219 )   Save In this study, we established cell models for Parkinson’s disease using rotenone. An RNA interference vector targeting Parkin-associated endothelin receptor-like receptor (Pael-R) was transfected into the model cells. The results of reverse-transcription polymerase chain reaction and western blot analysis showed that Pael-R expression was decreased after RNA interference compared with the control group (no treatment) and the model group (rotenone treatment), while the rate of apoptosis and survival of dopaminergic cells did not differ significantly between groups, as detected by flow cytometry and an MTT assay. These experimental findings indicate that the Pael-R gene has no role in the changes in rotenone-induced Parkinson’s disease model cells. Related Articles | Metrics

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Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson’s disease Long Teng, Fang Hong, Chenguang Zhang, Jiancheng He, Haiying Wang, 2014, 9 (4):  407-412.  doi: 10.4103/1673-5374.128246 Abstract ( 315 )   PDF (228KB) ( 4116 )   Save Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson’s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson’s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson’s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson’s disease by modulating neurotransmitter signaling in the corpus striatum. Related Articles | Metrics

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A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L Ruxu Zhang, Fufeng Zhang, Xiaobo Li, Shunxiang Huang, Xiaohong Zi, Ting Liu, Sanmei Liu, Xuning Li, Kun Xia, Qian Pan, Beisha Tang 2014, 9 (4):  413-419.  doi: 10.4103/1673-5374.128248 Abstract ( 201 )   PDF (1232KB) ( 1791 )   Save We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141NHSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the K141NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141NHSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141NHSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the K141NHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease. Related Articles | Metrics

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Local inhibition of GABA affects precedence effect in the inferior colliculus Yanjun Wang, Ningyu Wang, Dan Wang, Jun Jia, Jinfeng Liu, Yan Xie, Xiaohui Wen, Xiaoting Li 2014, 9 (4):  420-429.  doi: 10.4103/1673-5374.128250 Abstract ( 247 )   PDF (928KB) ( 1303 )   Save The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid (GABA). We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions: no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-aminobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect. Related Articles | Metrics

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7.0T nuclear magnetic resonance evaluation of the amyloid beta (1–40) animal model of Alzheimer’s disease: comparison of cytology verification Lei Zhang, Shuai Dong, Guixiang Zhao, Yu Ma 2014, 9 (4):  430-435.  doi: 10.4103/1673-5374.128255 Abstract ( 490 )   PDF (940KB) ( 1188 )   Save 3.0T magnetic resonance spectroscopic imaging is a commonly used method in the research of brain function in Alzheimer’s disease. However, the role of 7.0T high-field magnetic resonance spectroscopic imaging in brain function of Alzheimer’s disease remains unclear. In this study, 7.0T magnetic resonance spectroscopy showed that in the hippocampus of Alzheimer’s disease rats, the N-acetylaspartate wave crest was reduced, and the creatine and choline wave crest was elevated. This finding was further supported by hematoxylin-eosin staining, which showed a loss of hippocampal neurons and more glial cells. Moreover, electron microscopy showed neuronal shrinkage and mitochondrial rupture, and scanning electron microscopy revealed small size hippocampal synaptic vesicles, incomplete synaptic structure, and reduced number. Overall, the results revealed that 7.0T high-field nuclear magnetic resonance spectroscopy detected the lesions and functional changes in hippocampal neurons of Alzheimer’s disease rats in vivo, allowing the possibility for assessing the success rate and grading of the amyloid beta (1–40) animal model of Alzheimer’s disease. Related Articles | Metrics

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Circadian fluctuations in three types of sensory modules in healthy subjects Yong Hyun Kwon, Ki Seok Nam 2014, 9 (4):  436-439.  doi: 10.4103/1673-5374.128256 Abstract ( 284 )   PDF (168KB) ( 1624 )   Save This study was designed to observe and compare the circadian fluctuations in tactile sense, joint reposition sense and two-point discrimination in healthy subjects. Twenty-one healthy adult subjects received perceptual ability tests through these three different sensory modules at approximately 9:00, 13:00 and 18:00 in a day. The distribution of ranking for perceptual ability was significantly different among the three different time points in each individual, with highest perceptual ability in the evening compared with noon and morning, in terms of tactile sense and two-point discrimination. These findings suggest that the perceptual ability of healthy subjects fluctuates according to the time points in a day. Related Articles | Metrics

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Examination of Huntington’s disease in a Chinese family Mingxia Yu, Xiaogai Li, Sanyun Wu, Ji Shen, Jiancheng Tu 2014, 9 (4):  440-446.  doi: 10.4103/1673-5374.128258 Abstract ( 323 )   PDF (1708KB) ( 1585 )   Save We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington’s disease. Among 17 family members across three generations, four patients (II2, II6, III5, and III9) show typical Huntington’s disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members (II2, II6, and III5). Moreover, genetic analysis identified abnormally amplified CAG sequence repeats (> 40) in two members (III5 and III9). Among borderline cases, with clinical symptoms and brain imaging features of Huntington’s disease, two cases were identified (II2 and II6), but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington’s disease. Our findings suggest that clinical diagnosis of Huntington’s disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis. Related Articles | Metrics

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Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue: neuroprotective measures in the surgical treatment of epilepsy Yin SY, Feng KK, Feng M, Zhang XQ, Zhang YQ 2014, 9 (4):  447-448.  doi: 10.4103/1673-5374.128259 Abstract ( 242 )   PDF (1525KB) ( 1059 )   Save References | Related Articles | Metrics