Inhibition of dynein but not kinesin induces aberrant focal accumulation of neurofilaments within axonal neurites

Motil, Jennifer; Dubey, Maya; Chan, Walter K.‐H.; Shea, Thomas B.

doi:10.1016/j.brainres.2006.09.108

Cited by 22 publications

(12 citation statements)

References 66 publications

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“…Impaired function of both kinesin and dynein transport has been implicated in clinical ALS and in murine models of motor neuron disease (32)(33)(34)(35)(36)(37)(38)(39)(40). Moreover, we demonstrated that inhibition of dynein but not kinesin function induced aberrant NF accumulation within axonal neurites in culture (41). This initially counterintuitive observation is consistent with, and supported by, the above analyses of traffic jams.…”

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confidence: 89%

Traffic Jams: Dynamic Models for Neurofilament Accumulation in Motor Neuron Disease

Shea

Beaty

2007

Traffic

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supporting

confidence: 89%

Traffic Jams: Dynamic Models for Neurofilament Accumulation in Motor Neuron Disease

Shea

Beaty

2007

Traffic

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“…These changes can often affect very specific parts of transport such as different compartments of the axon or the direction of cargo movement away from the cell body or toward the cell body (Shea and Beaty, 2007). Due to the complexity of the nervous system, most of the evidence reporting differential transport effects in pathology are ex vivo (see for example, Brady et al, 1990; Morfini et al, 2007; Motil et al, 2007; Lee et al, 2011; LaPointe et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma

et al. 2014

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Axonal transport deficits have been reported as an early pathology in several neurodegenerative disorders, including glaucoma. However, the progression and mechanisms of these deficits are poorly understood. Previous work suggests that anterograde transport is affected earlier and to a larger degree than retrograde transport, yet this has never been examined directly in vivo. Using combined anterograde and retrograde tract tracing methods, we examined the time-course of anterograde and retrograde transport deficits in the retinofugal projection in pre-glaucomatous (3 month-old) and glaucomatous (9–13 month old) DBA/2J mice. DBA/2J-Gpnmb+ mice were used as a control strain and were shown to have similar retinal ganglion cell densities as C57BL/6J control mice—a strain commonly investigated in the field of vision research. Using cholera toxin-B injections into the eye and FluoroGold injections into the superior colliculus (SC), we were able to measure anterograde and retrograde transport in the primary visual projection. In DBA/2J, anterograde transport from the retina to SC was decreased by 69% in the 9–10 month-old age group, while retrograde transport was only reduced by 23% from levels seen in pre-glaucomatous mice. Despite this minor reduction, retrograde transport remained largely intact in these glaucomatous age groups until 13-months of age. These findings indicate that axonal transport deficits occur in semi-functional axons that are still connected to their brain targets. Structural persistence as determined by presence of estrogen-related receptor beta label in the superficial SC was maintained beyond time-points where reductions in retrograde transport occurred, also supporting that transport deficits may be due to physiological or functional abnormalities as opposed to overt structural loss.

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“…The bars represent mean and standard error values of healthy controls and 1,2 DAB diseased mice on day 45 of 1,2 DAB administration. The traces represent records of CMAP: proximal S1 from healthy and diseased mice (upper and lower traces, respectively) Neurotox Res (2011) 19:195-209 201 Kriz 2006, and also in ALS disease (Motil et al 2007;Strong 2003). Gelsolin's anti-apoptotic properties are also related to its dynamic actions on the cytoskeleton (Harms et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of the Combined Use of Growth Hormone Releasing Peptide-6 and Epidermal Growth Factor in an Axonopathy Model

et al. 2010

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Amyotrophic lateral sclerosis (ALS) is a disease of the central nervous system characterized by loss of spinal motor neurons, for which no effective treatment exists. Epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP-6) have been considered as good candidates for the treatment of this disease, due to their well documented effects in eliciting pleiotrophic and cell survival mechanisms. The aim of the present work was to evaluate the separate and combined effects of both peptides in an experimental animal model of ALS, the proximal axonopathy induced by 1,2 diacetylbenzene (1,2 DAB) in mice. The evaluations were conducted by means of behavioral tests (trapeze, tail suspension, gait pattern, and open field) and by recording the complex muscle action potential (CMAP) in three different hind limb segments: proximal S1, medial S2, and distal S3. Intraperitoneal daily administration of 1,2 DAB produced significant reduction in body weight, muscle strength, extensor reflex, spontaneous activity, and changes in gait pattern parameters. In parallel 1,2 DAB produced significant prolongation of onset latency and decrease in amplitude of CMAP and in the integrated complex action potential index. Daily administration of the separate compounds did not accelerate the recovery of the affected parameters, except for the gait pattern. The combined treatment produced significant improvement in behavioral parameters, as well as in electrophysiological recovery, particularly in the proximal segment of CMAP. The latter results confirm the proximal character of 1,2 DAB neuropathy, and suggest that combined therapy with EGF and GHRP-6 might be a good therapeutic strategy for the treatment of ALS.

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Inhibition of dynein but not kinesin induces aberrant focal accumulation of neurofilaments within axonal neurites

Cited by 22 publications

References 66 publications

Traffic Jams: Dynamic Models for Neurofilament Accumulation in Motor Neuron Disease

Traffic Jams: Dynamic Models for Neurofilament Accumulation in Motor Neuron Disease

Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma

Therapeutic Effect of the Combined Use of Growth Hormone Releasing Peptide-6 and Epidermal Growth Factor in an Axonopathy Model

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