Abstract:
:Paclitaxel is an effective chemotherapeutic agent that, despite its common use, often causes peripheral sensory neuropathy. In neurons, paclitaxel binds to and stabilizes microtubules, and through unknown mechanisms, bundles microtubules and disrupts their organization. Because microtubules serve as tracks on which a variety of axonal cargoes are transported, a leading hypothesis for the etiology of paclitaxel-induced neuropathy is that these changes to microtubule organization impair axonal transport. In addition to supporting transport, microtubules also serve a structural role, accommodating axonal extension occurring during axonal growth or joint movement. In light of this dual role for microtubules, we tested the hypothesis that axonal stretch amplified the effects of paclitaxel on axonal transport. Embryonic rat dorsal root ganglia were cultured on stretchable silicone substrates, and parameters describing the axonal transport of three distinct cargoes--mitochondria, synaptophysin, and actin--were measured with and without paclitaxel treatment and axonal strain. Paclitaxel treatment, particularly in combination with stretch, led to severe perturbations in several transport parameters, including the number, velocity, and travel distance of cargoes in the axon. Our results suggest that mechanical loading of neurons can exacerbate transport deficits associated with paclitaxel treatment, raising the interesting possibility that paclitaxel influences neuronal function in a multi-factorial manner.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Bober BG,Gutierrez E,Plaxe S,Groisman A,Shah SBdoi
10.1016/j.expneurol.2015.06.023subject
Has Abstractpub_date
2015-09-01 00:00:00pages
358-67eissn
0014-4886issn
1090-2430pii
S0014-4886(15)30032-7journal_volume
271pub_type
杂志文章abstract::Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulato...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.01.011
更新日期:2014-04-01 00:00:00
abstract::Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. In this study, we analyzed the expression and function of desmoplakin in peripheral nerve regeneration. Desmo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2014.12.005
更新日期:2015-02-01 00:00:00
abstract::Most neurons in the dorsal neostriatum die 1 day after 30 min of cerebral ischemia. Dopamine may play a role in the pathogenesis of neuronal injury in neostriatum following ischemia. It has been shown that the number of surviving neurons in the right neostriatum dramatically increased following ischemia after lesions ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7074
更新日期:1999-07-01 00:00:00
abstract::Adeno-associated virus (AAV) vectors are derived from a nonpathogenic and defective human parvovirus. Although currently unable to display the integration specificity featured by its wild-type parent, the recombinant AAV (rAAV) system has continued to attract enormous interest primarily due to its unique features such...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1006/exnr.1996.6396
更新日期:1997-03-01 00:00:00
abstract::Graft-induced dyskinesia has emerged as a problematic side effect after transplantation of fetal dopamine cells into the striatum of patients with Parkinson's disease. These adverse effects of dystonic and choreatiform hyperkinesias that persisted even after withdrawal of L-DOPA medication are not yet fully understood...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.09.017
更新日期:2011-12-01 00:00:00
abstract::The extent and kinetic profiles of lipid peroxidation induced with Fe2+-ascorbic acid in a homogenate of spinal cord from greyhound dogs were ascertained by measurement of the formation of malondialdehyde (MDA) and chemiluminescence in the presence of four drugs. Changes in MDA and chemiluminescence were correlated as...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(83)90338-2
更新日期:1983-09-01 00:00:00
abstract::As in Alzheimer's disease, brains of Guam Chamorros with amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) contain intraneuronal-paired helical filaments composed of accumulated phosphorylated tau protein. Tau mRNA expression in rat neuronal cultures-normally modulated by glutamate-increases ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1998.6962
更新日期:1999-01-01 00:00:00
abstract::Opening of the mitochondrial permeability transition pore has increasingly been implicated in excitotoxic, ischemic, and apoptotic cell death, as well as in several neurodegenerative disease processes. However, much of the work directly characterizing properties of the transition pore has been performed in isolated li...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7438
更新日期:2000-08-01 00:00:00
abstract::In birds, a variety of subtotal thoracic spinal cord lesions were made to determine the spinal cord pathways essential for avian hind limb locomotion (bipedal walking). The various surgical disruptions included: section of the dorsal half of the cord, a hemisection, section of the dorsal cord and ventromedial funiculi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90148-8
更新日期:1987-02-01 00:00:00
abstract::Dopaminergic (DAergic) hypofunction in the medial prefrontal cortex (mPFC) has been implicated in the negative and cognitive symptoms of schizophrenia and is regulated by serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN). The lateral habenula (LHb) is a key element in controlling DRN 5-HT neurons. We ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2019.05.005
更新日期:2019-08-01 00:00:00
abstract::Mitochondrial dysfunction and pathology that contribute to a host of neurodegenerative diseases are deduced from changes in ultrastructure, routinely examined by a host of optical techniques. We adapted the technique of photon correlation spectroscopy (PCS) to evaluate calcium-induced structural alterations in isolate...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2005.10.002
更新日期:2006-02-01 00:00:00
abstract::The present study evaluated the growth potential and differentiation of human fetal spinal cord (FSC) tissue in the injured adult rat spinal cord under different lesion and grafting conditions. Donor tissue at 6-9 weeks of gestational age was obtained through elective abortions and transplanted either immediately into...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6703
更新日期:1997-12-01 00:00:00
abstract::Macrophage colony stimulating factor (M-CSF) is a cytokine that regulates the survival, proliferation and maturation of microglial cells. Administration of M-CSF can promote neuronal survival in various models of central nervous system (CNS) injury. Here, in an attempt to induce a neuroprotective microglial cell pheno...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2009.08.021
更新日期:2009-12-01 00:00:00
abstract::After injury of their axons, damaged neurons shift their metabolic activity into a reparative mode aimed at survival and regeneration or, alternatively, they undergo degeneration and die. Previous reports have shown that at the initial stages of the response to axonal injury, polyamines are essential for neuronal surv...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(86)90307-9
更新日期:1986-06-01 00:00:00
abstract::We recently reported structural changes in nodes of Ranvier of frog dorsal roots that are associated with activation at 20 or 50 Hz for 15 min. The structural effects co-occur with alterations in the latency, amplitude, and waveform of the compound action potential. The alterations in nodal morphology include formatio...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(88)90067-2
更新日期:1988-07-01 00:00:00
abstract::Abuse of stimulant drugs such as methamphetamine (METH) and cocaine has been associated with long-lasting persistent behavioral alterations. Although METH-induced changes in the striatal dopaminergic system might play a role in these effects, the potential underlying neuroanatomical substrate for the chronic cognitive...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.05.023
更新日期:2007-09-01 00:00:00
abstract::Alpha-synuclein (alphaSN) is implicated in Parkinson's disease (PD) and is the major component of Lewy bodies (LBs). Although alphaSN is mainly expressed in neuronal cells and exists as a cytoplasmic protein, it has been found in body fluids including cerebrospinal fluid and blood. This study explored plasma alphaSN a...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.12.006
更新日期:2007-04-01 00:00:00
abstract::beta-N-methylamino-l-alanine (BMAA) is a non-protein amino acid implicated in the neurodegenerative disease amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC) on Guam. BMAA has recently been discovered in the brains of Alzheimer's patients in Canada and is produced by various species of cyanobacteria a...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2009.04.002
更新日期:2009-06-01 00:00:00
abstract::The neural substrate underlying the aversive effects induced by ethanol abstinence is still unclear. One candidate for such effects is the dorsal periaqueductal gray (dPAG), a core structure of the brain aversion system. The main aim of this study is to examine the role of the dPAG as a possible locus of the aversive ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.02.004
更新日期:2006-07-01 00:00:00
abstract::To compare the evolution of cell body responses to two different types of axonal injuries--sciatic nerve crush (axotomy) and chronic 2,5-hexanedione-induced neuropathy--we studied rat lumbar dorsal root ganglion neurons with light microscopy and morphometry. Compared with control neurons, axotomized cells showed early...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90100-1
更新日期:1985-08-01 00:00:00
abstract::We assessed the potential of different MRI measures to detect and quantify skeletal muscle changes with denervation in two mouse models of denervation/neurogenic atrophy. Acute complete denervation and chronic partial denervation were examined in calf muscles after sciatic nerve axotomy and in transgenic SOD1(G93A) mi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.04.033
更新日期:2008-08-01 00:00:00
abstract::The present study evaluates the temporal relationships between increases in glial fibrillary acidic protein (GFAP) mRNA, GFA protein levels, and GFAP immunostaining in the hippocampus of adult rats following unilateral lesions of the entorhinal cortex (EC). GFAP mRNA levels were assessed at 12 h, 1, 2, 4, 6, 8, 10, 12...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1993.1187
更新日期:1993-12-01 00:00:00
abstract::The repair of nerve gap injuries with tubular nerve guides has been used extensively as an in vivo test model in identifying substances which may enhance nerve regeneration. The model has also been used clinical nerve repair. The objective of this study was to compare three different gel matrix-forming materials as po...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6543
更新日期:1997-08-01 00:00:00
abstract::Neural progenitor cells (NPCs) grafted to sites of spinal cord injury (SCI) extend numerous axons over long distances and form new synaptic connections with host neurons. In the present study we examined the myelination of axons emerging from NPC grafts. Rat embryonic day 14 (E14) multipotent NPCs constitutively expre...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.07.005
更新日期:2017-10-01 00:00:00
abstract::The effects of unilateral intrahippocampal injection of kainic acid, a potent neuroexcitant and neurotoxin, on subsequent susceptibility to kindling of the contralateral hippocampus or contralateral amygdala were investigated in albino rats. At the chosen doses (0.20 to 1.25 micrograms dissolved in physiologic saline)...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90087-2
更新日期:1987-08-01 00:00:00
abstract::Alzheimer's disease is associated with an age-related accumulation of Abeta and inflammation. The inflammatory mediator, TNFalpha activates a signaling cascade involving NFkappaB translocation to the nucleus and a beneficial or detrimental transcriptional response, depending on the age of the neurons and the type of s...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.05.007
更新日期:2008-09-01 00:00:00
abstract::Abnormal corticostriatal plasticity is a key mechanism of L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). Antagonists at glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, such as IEM 1460, reduce induction and expression of dyskinesia in rat and non-human primate models ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2013.01.019
更新日期:2013-09-01 00:00:00
abstract::The aminergic and cholinergic fibers innervating the hippocampus reach their target regions via the dorsal (dorsal fornix, fimbria, and cingulum) and ventral routes. The plasticity of this innervation after lesions of the dorsal pathway was investigated in the septal, medial, and temporal regions of the adult rat hipp...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(87)90053-7
更新日期:1987-05-01 00:00:00
abstract::Bone marrow stromal cells (BMSC) have been shown to generate neural cells under experimental conditions in vitro and following transplantation into animal models of stroke and traumatic CNS injury. Hastened recovery from the neurological deficit has not correlated with structural repair of the lesion in the stroke mod...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2003.09.003
更新日期:2004-01-01 00:00:00
abstract::Spinal axons in the larval sea lamprey regenerate following a complete spinal transection. It is not known whether regenerating growth cones require contact with cellular elements or whether the basement membrane and collagenous meninx primitiva which surround the spinal cord are sufficient for neurite out-growth. To ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(91)90114-r
更新日期:1991-04-01 00:00:00