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Retrograde Direction (retrograde + direction)
Selected AbstractsHigh-resolution imaging demonstrates dynein-based vesicular transport of activated trk receptorsDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2002Anita Bhattacharyya Abstract Target-derived neurotrophins signal from nerve endings to the cell body to influence cellular and nuclear responses. The retrograde signal is conveyed by neurotrophin receptors (Trks) themselves. To accomplish this, activated Trks may physically relocalize from nerve endings to the cell bodies. However, alternative signaling mechanisms may also be used. To identify the vehicle wherein the activated Trks are located and transported, and to identify associated motor proteins that would facilitate transport, we use activation-state specific antibodies in concert with immunoelectron microscopy and deconvolution microscopy. We show that the activated Trks within rat sciatic nerve axons are preferentially localized to coated and uncoated vesicles. These vesicles are moving in a retrograde direction and so accumulate distal to a ligation site. The P-Trk containing vesicles, in turn, colocalize with dynein components, and not with kinesins. Collectively, these results indicate activated Trk within axons travel in vesicles and dynein is the motor that drives these vesicles towards the cell bodies. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 302,312, 2002 [source] Cerebral Hemodynamics Changes During Retrograde Brain Perfusion in DogsJOURNAL OF NEUROIMAGING, Issue 2 2001Alexander Y. Razumovsky PhD ABSTRACT The objective of this study was to examine cerebral hemodynamics changes during hypothermic circulatory arrest (HCA) with and without retrograde cerebral perfusion (RCP). Thirteen colony-bred hound dogs were placed on cardiopulmonary bypass (CPB) and cooled to 18°C. Five dogs underwent 2 hours of HCA without RCP and 8 with RCP. The animals were then rewarmed on CPB until normothermic and weaned. Cerebral blood flow velocity (CBFV) and Gosling Pulsatility Index (PI) in the middle cerebral artery (MCA) were studied using transcranial Doppler (TCD) ultrasound. At baseline and during pre- and postarrest CPB, there was anterograde direction of blood flow in the MCA. During HCA with RCP, there was retrograde direction of blood flow in the MCA. There was no difference in CBFV between pre-, during, and postarrest CPB in the group with RCP; however, there was significantly increased CBFV during postarrest CPB in the group without RCP compared to the dogs with RCP. Later, at 3 hours after postarrest CPB, there was decreased CBFV in all animals accompanied by increased PI (2.4 ± 0.4 and 2.2 ± 0.6 for animals with RCP and without RCP, respectively) and abnormal TCD waveform changes including decreased diastolic compartment and sharp systolic peak. During hypothermic circulatory arrest, RCP provides CBFV in the MCA comparable to MCA CBFV during CPB. HCA dogs without RCP showed immediate hyperemia on reperfusion. The decreased CBFV and increased PI at 1 hour after postarrest CPB could be an indicator of progressive ischemic injury due to the increased intracranial pressure despite the implementation of RCP. [source] Multimodal microglia imaging of fiber tracts in acute subcortical stroke,ANNALS OF NEUROLOGY, Issue 6 2009Basia A. Radlinska BSc Objective Case series with 11C-PK11195 and positron emission tomography (PET) in stroke patients suggest that activated microglia may be detected in remote brain regions with fiber tract connections to the lesion site as an indicator of poststroke neuroinflammation. However, the specificity of these imaging findings remains to be demonstrated. Methods In a prospective controlled study, we measured microglia activity using 11C-PK11195-PET along the pyramidal tract, as defined by diffusion tensor imaging, in 21 patients with first-time acute subcortical ischemia within 2 weeks of stroke. Uptake ratios (affected vs unaffected side) were determined for a set of standardized volumes of interest along the pyramidal tracts (PT). Uptake ratios from patients in whom the PT was affected were compared with those in whom the PT was not affected. Uptake ratios were related to motor deficit and lesion size according to correlation analyses. Results Increased uptake ratios were only found in patients in whom the PT was affected by stroke. In the affected hemisphere, uptake was increased at the level of pons, midbrain, and internal capsule, but not in the oval center. The extent of remote microglia activation was independent of infarct size or clinical measures of stroke severity. Interpretation A specific activation of microglia was only found in patients in whom the PT was affected by the stroke and only caudal (anterograde) to the lesion; no activation was found in the retrograde direction or in those patients in whom the PT was not affected. These findings were independent of infarct size and may represent changes secondary to early Wallerian degeneration. Ann Neurol 2009;66:825,832 [source] Transport of neurofilaments in growing axons requires microtubules but not actin filamentsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005Franto Francis Abstract Neurofilament (NF) polymers are conveyed from cell body to axon tip by slow axonal transport, and disruption of this process is implicated in several neuronal pathologies. This movement occurs in both anterograde and retrograde directions and is characterized by relatively rapid but brief movements of neurofilaments, interrupted by prolonged pauses. The present studies combine pharmacologic treatments that target actin filaments or microtubules with imaging of NF polymer transport in living axons to examine the dependence of neurofilament transport on these cytoskeletal systems. The heavy NF subunit tagged with green fluorescent protein was expressed in cultured sympathetic neurons to visualize NF transport. Depletion of axonal actin filaments by treatment with 5 ,M latrunculin for 6 hr had no detectable effect on directionality or transport rate of NFs, but frequency of movement events was reduced from 1/3.1 min of imaging time to 1/4.9 min. Depolymerization of axonal microtubules using either 5 ,M vinblastine for 3 hr or 5 ,g/ml nocodazole for 4,6 hr profoundly suppressed neurofilament transport. In 92% of treated neurons, NF transport was undetected. These observations indicate that actin filaments are not required for neurofilament transport, although they may have subtle effects on neurofilament movements. In contrast, axonal transport of NFs requires microtubules, suggesting that anterograde and retrograde NF transport is powered by microtubule-based motors. © 2005 Wiley-Liss, Inc. [source] Trafficking of macromolecules and organelles in cultured Dystonia musculorum sensory neurons is normalTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2006Madeline Pool Abstract Dystonia musculorum (dt) mice suffer from a recessive neuropathy characterized by the progressive loss of sensory axons. The gene responsible for this disorder, dystonin/Bpag1, encodes several alternatively spliced forms of a cytoskeletal linker protein. Neural isoforms of dystonin/Bpag1 are predicted to link actin filaments to microtubules. Consistent with this, previous observations have demonstrated that the cytoskeleton within sensory neurites of dt mice is perturbed. Also, recent results have indicated that a neural isoform of dystonin/Bpag1 interacts with the dynein motor complex. Because microtubule organization and dynein motor function are essential for trafficking, we hypothesized that this process would be perturbed in dt sensory neurons. Here, we demonstrate that cultured primary dorsal root ganglion (DRG) neurons express dystonin/Bpag1 and that loss of this expression causes an increase in apoptosis and a decrease in average neurite length. In contrast, detailed examination showed that the organization of microtubules is indistinguishable in DRG neuronal cultures from neonatal dt and wild-type mice. In addition, the steady-state distribution of several molecules and organelles is unchanged in these cultures. Furthermore, the speeds of mitochondrial movement in both anterograde and retrograde directions were comparable in dt and wild-type sensory neurons cultured from neonatal mice. Thus, dystonin/Bpag1 is not essential for microtubule network assembly since the microtubule network is intact in short-term cultures of sensory neurons from neonatal mice lacking this protein. In addition, dystonin/Bpag1 is not an essential part of the dynein motor complex for mitochondrial transport since mitochondrial trafficking is normal in cultured sensory neurons from dt mice. J. Comp. Neurol. 494:549,558, 2006. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||