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15 May 2012, Volume 7 Issue 14 Previous Issue    Next Issue

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The neural butterfly effect The injury to peripheral nerves changes the brain Guest Editor: Krzysztof Czaja 2012, 7 (14):  1045-1046.  Abstract ( 176 )   PDF (42KB) ( 751 )   Save Regeneration of damaged innervations in the peripheral nervous system (PNS) has been well documented in both animals and human[1]. After injury, the damaged neurite swells and undergoes retrograde degeneration. Once the debris is cleared, it begins to sprout and restore damaged connections. Damaged axons are able to regrow as long as the perikarya are intact and have made contact with the Schwann cells in the endoneurial channel[2]. Under appropriate conditions, regenerating axons may reinnervate the original target and restore connections and function. This scenario, however, shows only a fraction of events following the injury to the PNS. Papers published in this issue of NRR go beyond the injured neuron and present the data showing the consequences of PNS damage in the central nervous system (CNS). They also discuss the possibility that factors regulating neural proliferation and differentiation in the developing nervous system may be recapitulated after injury and contribute to neural proliferation and adult neurogenesis. Related Articles | Metrics

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Neurogenesis in the adult peripheral nervous system Krzysztof Czaja, Michele Fornaro, Stefano Geuna 2012, 7 (14):  1047-1054.  Abstract ( 217 )   PDF (111KB) ( 945 )   Save Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system. References | Related Articles | Metrics

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Hippocampal plasticity after a vagus nerve injury in the rat Giulia Ronchi, Vitaly Ryu, Michele Fornaro, Krzysztof Czaja 2012, 7 (14):  1055-1063.  Abstract ( 305 )   PDF (249KB) ( 946 )   Save Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus, leading to alteration of neurogenesis. Related Articles | Metrics

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Exogenous reference gene normalization for real-time reverse transcription-polymerase chain reaction analysis under dynamic endogenous transcription Stephen Johnston, Zachary Gallaher, Krzysztof Czaja 2012, 7 (14):  1064-1072.  Abstract ( 314 )   PDF (170KB) ( 1099 )   Save Quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is widely used to investigate transcriptional changes following experimental manipulations to the nervous system. Despite the widespread utilization of qPCR, the interpretation of results is marred by the lack of a suitable reference gene due to the dynamic nature of endogenous transcription. To address this inherent deficiency, we investigated the use of an exogenous spike-in mRNA, luciferase, as an internal reference gene for the 2-ΔΔCt normalization method. To induce dynamic transcription, we systemically administered capsaicin, a neurotoxin selective for C-type sensory neurons expressing the TRPV-1 receptor, to adult male Sprague-Dawley rats. We later isolated nodose ganglia for qPCR analysis with the reference being either exogenous luciferase mRNA or the commonly used endogenous reference β-III tubulin. The exogenous luciferase mRNA reference clearly demonstrated the dynamic expression of the endogenous reference. Furthermore, variability of the endogenous reference would lead to misinterpretation of other genes of interest. In conclusion, traditional reference genes are often unstable under physiologically normal situations, and certainly unstable following the damage to the nervous system. The use of exogenous spike-in reference provides a consistent and easily implemented alternative for the analysis of qPCR data. Related Articles | Metrics

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Respiratory neuroplasticity following carotid body denervation Central and peripheral adaptations Matthew R. Hodges, Hubert V. Forster 2012, 7 (14):  1073-1079.  Abstract ( 215 )   PDF (227KB) ( 1089 )   Save Historically, the role of the carotid bodies in ventilatory control has been understated, but the current view suggests that the carotid bodies (1) provide a tonic, facilitory input to the respiratory network, (2) serve as the major site of peripheral O2 chemoreception and minor contributor to CO2/H+ chemoreception, and (3) are required for ventilatory adaptation to high altitude. Each of these roles has been demonstrated in studies of ventilation in mammals after carotid body denervation. Following carotid body denervation, many of the compromised ventilatory “functions” show a time-dependent recovery plasticity that varies in the degree of recovery and time required for recovery. Respiratory plasticity following carotid body denervation is also dependent on species, with contributions from peripheral and central sites/mechanisms driving the respiratory plasticity. The purpose of this review is to provide a summary of the data pointing to peripheral and central mechanisms of plasticity following carotid body denervation. We speculate that after carotid body denervation there are altered excitatory and/or inhibitory neuromodulator mechanisms that contribute to the initial respiratory depression and the subsequent respiratory plasticity, and further suggest that the continued exploration of central effects of carotid body denervation might provide useful information regarding the capacity of the respiratory network for plasticity following neurologic injury in humans. References | Related Articles | Metrics

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Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice Tao Wang1, Yanyong Liu2, Nan Yang2, Chao Ji2, Piu Chan1, Pingping Zuo2 2012, 7 (14):  1080-1087.  Abstract ( 224 )   PDF (168KB) ( 1054 )   Save Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson’s disease. Oral administration of octacosanol (100 mg/kg) significantly improved behavioral impairments in mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signal transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson’s disease. Related Articles | Metrics

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Inhibiting p38 mitogen-activated protein kinase attenuates cerebral ischemic injury in Swedish mutant amyloid precursor protein transgenic mice Liangyu Zou, Haiyan Qin, Yitao He, Heming Huang, Yi Lu, Xiaofan Chu 2012, 7 (14):  1088-1109.  Abstract ( 220 )   PDF (438KB) ( 775 )   Save Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB239063 into Swedish mutant amyloid precursor protein (APP/SWE) transgenic and non-transgenic mice. The number of surviving neurons in the penumbra was quantified using Nissl staining, and the activity of p38 MAPKs was measured by western blotting. The number of surviving neurons in the penumbra was significantly reduced in APP/SWE transgenic mice compared with non-transgenic controls 7 days after cerebral ischemia, but the activity of p38 MAPKs was significantly elevated compared with the non-ischemic hemisphere in the APP/SWE transgenic mice. SB239063 prevented these changes. The APP/SWE mutation exacerbated ischemic brain injury, and this could be alleviated by inhibiting p38 MAPK activity. References | Related Articles | Metrics

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Overexpression of estrogen receptor beta alleviates the toxic effects of beta-amyloid protein on PC12 cells via non-hormonal ligands Hui Wang, Lihui Si, Xiaoxi Li, Weiguo Deng, Haimiao Yang, Yuyan Yang, Yan Fu 2012, 7 (14):  1095-1100.  Abstract ( 207 )   PDF (180KB) ( 950 )   Save After binding to the estrogen receptor, estrogen can alleviate the toxic effects of beta-amyloid protein, and thereby exert a therapeutic effect on Alzheimer’s disease patients. Estrogen can increase the incidence of breast carcinoma and endometrial cancer in post-menopausal women, so it is not suitable for clinical treatment of Alzheimer’s disease. There is recent evidence that the estrogen receptor can exert its neuroprotective effects without estrogen dependence. Real-time quantitative PCR and flow cytometry results showed that, compared with non-transfected PC12 cells, adenovirus-mediated estrogen receptor β gene-transfected PC12 cells exhibited lower expression of tumor necrosis factor α and interleukin 1β under stimulation with beta-amyloid protein and stronger protection from apoptosis. The Akt-specific inhibitor Abi-2 decreased the anti-inflammatory and anti-apoptotic effects of estrogen receptor β gene-transfection. These findings suggest that overexpression of estrogen receptor β can alleviate the toxic effect of beta-amyloid protein on PC12 cells, without estrogen dependence. The Akt pathway is one of the potential means for the anti-inflammatory and anti-apoptotic effects of the estrogen receptor. Related Articles | Metrics

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Cell viability and dopamine secretion of 6-hydroxydopamine-treated PC12 cells co-cultured with bone marrow-derived mesenchymal stem cells Yue Tang, Yongchun Cui, Fuliang Luo, Xiaopeng Liu, Xiaojuan Wang, Aili Wu, Junwei Zhao, Zhong Tian, Like Wu 2012, 7 (14):  1101-1105.  Abstract ( 213 )   PDF (210KB) ( 980 )   Save In the present study, PC12 cells induced by 6-hydroxydopamine as a model of Parkinson’s Disease, were used to investigate the protective effects of bone marrow-derived mesenchymal stem cells bone marrow-derived mesenchymal stem cells against 6-hydroxydopamine-induced neurotoxicity and to verify whether the mechanism of action relates to abnormal α-synuclein accumulation in cells. Results showed that co-culture with bone marrow-derived mesenchymal stem cells enhanced PC12 cell viability and dopamine secretion in a cell dose-dependent manner. MitoLight staining was used to confirm that PC12 cells co-cultured with bone marrow-derived mesenchymal stem cells demonstrate reduced levels of cell apoptosis. Immunocytochemistry and western blot analysis found the quantity of α-synuclein accumulation was significantly reduced in PC12 cell and bone marrow-derived mesenchymal stem cell co-cultures. These results indicate that bone marrow-derived mesenchymal stem cells can attenuate 6-hydroxydopamine-induced cytotoxicity by reducing abnormal α-synuclein accumulation in PC12 cells. Related Articles | Metrics

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Effects of cytokines and chemokines on   migration of mesenchymal stem cells following spinal cord injury Longyun Li, Maoguang Yang, Chunxin Wang, Qiheng Zhao, Jian Liu, Chuanguo Zhan, Zhi Liu, Xuepeng Li, Weihua Wang, Xiaoyu Yang 2012, 7 (14):  1106-1112.  Abstract ( 198 )   PDF (115KB) ( 860 )   Save We investigated the effects of cytokines and chemokines and their associated signaling pathways on mesenchymal stem cell migration after spinal cord injury, to determine their roles in the curative effects of mesenchymal stem cells. This study reviewed the effects of tumor necrosis factor-α, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin like growth factor-1, stromal cell-derived factor and monocyte chemoattractant protein-1, 3 during mesenchymal stem cell migration to damaged sites, and analyzed the signal transduction pathways involved in their effects on mesenchymal stem cell migration. The results confirmed that phosphatidylinositol 3-kinase/serine/threonine protein kinases and nuclear factor-κB play crucial roles in the migration of mesenchymal stem cells induced by cytokines and chemokines. Related Articles | Metrics

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Altered serous levels of monoamine neurotransmitter metabolites in patients with refractory and non-refractory depression Guiqing Zhang, Yanxia Zhang, Jianxia Yang, Min Hu, Yueqi Zhang, Xia Liang 2012, 7 (14):  1113-1118.  Abstract ( 203 )   PDF (81KB) ( 859 )   Save The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression (TRD) and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment. Related Articles | Metrics