The relation of axonal transport of mitochondria with microtubules and other axoplasmic organelles.

Friede, Reinhard L.; Ho, K C

doi:10.1113/jphysiol.1977.sp011727

Cited by 44 publications

(21 citation statements)

References 25 publications

(27 reference statements)

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“…20,[23][24][25][26][27] Interestingly, we found increased intra-axonal mitochondria in normally myelinated, remyelinated, and demyelinated axons of 192-day-infected mice when compared to the myelinated axons of sham-infected controls. The reason for increased mitochondria in injured axons is not completely understood, but may reflect oxidative stress, 52 impaired axonal transport, 25 attempts at restoring conduction, 27 and/or axonal regeneration. 53 Strong correlation coefficients were obtained between the percentage of total spinal cord demyelination and intra-axonal mitochondria for normally myelinated and demyelinated axons.…”

Section: Discussionmentioning

confidence: 86%

“…20,[23][24][25][26][27] We quantified the number of intra-axonal mitochondria for normally myelinated, remyelinated, and demyelinated axons in infected mice to gauge the overall health of axons within a demyelinated lesion ( Figure 5A). Mitochondria quantified in the myelinated axons of sham-infected mice were used as controls.…”

Section: Intraaxonal Mitochondria Are Increased In Demyelinated Lesionsmentioning

confidence: 99%

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Quantitative Ultrastructural Analysis of a Single Spinal Cord Demyelinated Lesion Predicts Total Lesion Load, Axonal Loss, and Neurological Dysfunction in a Murine Model of Multiple Sclerosis

Sathornsumetee

McGavern

Ure

et al. 2000

The American Journal of Pathology

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Infection of susceptible mice with Theiler's murine encephalomyelitis virus results in neurological dysfunction from progressive central nervous system demyelination that is pathologically similar to the human disease, multiple sclerosis. We hypothesized that the development of neuropathology proceeds down a final common pathway that can be accurately quantified within a single spinal cord lesion. To test this hypothesis, we conducted quantitative ultrastructural analyses of individual demyelinated spinal cord lesions from chronically infected mice to determine whether pathological variables assessed within a single lesion accurately predicted global assessments of morphological and functional disease course. Within lesions we assessed by electron microscopy the frequencies of normally myelinated, remyelinated, and demyelinated axons, as well as degenerating axons and intra-axonal mitochondria. The frequency of medium and large remyelinated fibers within a single lesion served as a powerful indicator of axonal preservation and correlated with preserved neurological function. The number of degenerating axons and increased intra-axonal mitochondria also correlated strongly with global measures of disease course, such as total lesion load, spinal cord atrophy, and neurological function. This is the first study to demonstrate that functional severity of disease course is evident within a single demyelinated lesion analyzed morphometrically at the ultrastructural level. The role of axonal injury in the development of permanent neurological dysfunction is an important focus of research studying central nervous system (CNS) demyelinating diseases in humans. Multiple sclerosis (MS) is the most common CNS demyelinating disease in humans, 1 and recent studies describing the extent of axonal injury in MS lesions have stimulated new interest in the role of axonal loss in long-term neurological disability during the course of this disease. 2,3 Despite the numerous reports of axonal pathology in MS patients, axonal damage after chronic demyelination is not completely understood. Therefore, the study of axonal loss in animal models of demyelinating disease may aid in the understanding of disease pathogenesis and the development of potential treatment strategies.Theiler's murine encephalomyelitis virus (TMEV) causes a chronic progressive demyelinating disease in susceptible strains of mice that is pathologically indistinguishable from MS. 4 -9 Intracerebral injection of TMEV into mice of the prototypic susceptible background (SJL/J) results in a biphasic disease characterized by an acute neuronal polioencephalitis followed by chronic white matter demyelination and neurological deficits. 10 Twenty-one days after postinfection, viral persistence is observed in oligodendrocytes, not neurons, and therefore, should not contribute directly to progressive neuronal disruption. 11,12 During the chronic phase of disease, multifocal demyelinating lesions are primarily localized to the white matter of the brain stem and spinal cord, and th...

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Section: Discussionmentioning

confidence: 86%

Section: Intraaxonal Mitochondria Are Increased In Demyelinated Lesionsmentioning

confidence: 99%

Quantitative Ultrastructural Analysis of a Single Spinal Cord Demyelinated Lesion Predicts Total Lesion Load, Axonal Loss, and Neurological Dysfunction in a Murine Model of Multiple Sclerosis

Sathornsumetee

McGavern

Ure

et al. 2000

The American Journal of Pathology

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“…The critical temperature for transport of DBH in bullfrog nerves, 10 0, is if anything slightly higher than the critical temperature for retrograde transport of organelles in myelinated axons of these nerves (Forman, Padjen & Siggins, 1977 (Friede & Ho, 1977 (Brimijoin, 1975;Brimijoin & Wiermaa, 1977, 1978. Also, giant axons in Aply-sia californica can transport extra material when their collateral branches are ligated (Goldberg, Goldman & Schwartz, 1976 (Chang, 1972;Byers, 1974;Friede & Ho, 1977). The hypothesis also accounts for our finding that the critical temperature for transport is lower than is required to induce depolymerization of microtubules.…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, the orders of potency of these drugs as inhibitors of transport and as inhibitors of microtubular assembly are similar (Banks & Till, 1975). Thirdly, in the case of the few antimitotic drugs examined in detail, the doses required to block transport are at least roughly similar S. BRIMIJOIN, J. OLSEN AND R. ROSENSON to those required to induce depolymerization of tubules in axons of the same nerve (Banks, Mayor & Tomlinson, 1971;Friede & Ho, 1977).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the temperature‐dependence of rapid axonal transport and microtubules in nerves of the rabbit and bullfrog.

Brimijoin¹,

Olsen²,

Rosenson³

1979

The Journal of Physiology

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SUMMARY1. The average velocity of transport of dopamine-fl-hydroxylase, an enzyme confined to unmyelinated adrenergic nerves, was measured in rabbit and bullfrog sciatic nerves or branches incubated in vitro at various temperatures. In parallel experiments, the number and density of microtubules were measured in crosssections of randomly selected unmyelinated axons from another set of nerves incubated under the same conditions. 2. Average transport velocity was exponentially related to temperature over a wide range, but it fell abruptly towards zero at temperatures below 13 0C in the case of rabbit nerves and 10 0C in the case of frog nerves.3. The number of microtubules per unmyelinated axon had declined considerably before the transport of dopamine-fl-hydroxylase was impaired. At 13 0C, axons in rabbit nerves lost 30 % of their microtubules. Axons in bullfrog nerves were, if anything, more sensitive to cold, losing 35 % of their microtubules at 15 0C and 65 % of them at 100 C. 4. Since the temperature-dependence of the axonal transport of dopamine-flhydroxylase is probably typical of rapid axonal transport in general, it was concluded that transport in unmyelinated axons can continue unaffected when a substantial fraction of the microtubular population has been lost. 5. Although these results could imply that microtubules are not essential for transport, they are equally compatible with the view that these organelles determine the capacity of the transport system and are normally present in excess.

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“…Throughout the cell, mitochondrial potential is heterogeneous and varies in time and space in response to changes in metabolic demand (Bindokas et al, 1998;Collins et al, 2002;Overly et al, 1996;Smiley et al, 1991;Wong-Riley, 1989). A link is assumed, but the relationship between mitochondrial ATP production and transport remains unclear (Bereiter-Hahn and Voth, 1983;Friede and Ho, 1977;Hollenbeck et al, 1985;Martenson et al, 1995;Ochs and Hollingsworth, 1971;Ochs and Smith, 1971).…”

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confidence: 99%

Axonal mitochondrial transport and potential are correlated

Miller

Sheetz

2004

Journal of Cell Science

457

387

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Disruption of axonal transport leads to a disorganized distribution of mitochondria and other organelles and is thought to be responsible for some types of neuronal disease. The reason for bidirectional transport of mitochondria is unknown. We have developed and applied a set of statistical methods and found that axonal mitochondria are uniformly distributed. Analysis of fast axonal transport showed that the uniform distribution arose from the clustering of the stopping events of fast axonal transport in the middle of the gaps between stationary mitochondria. To test whether transport was correlated with ATP production, we added metabolic inhibitors locally by micropipette. Whereas applying CCCP (a mitochondrial uncoupler) blocked mitochondrial transport, as has been previously reported, treatment with antimycin (an inhibitor of electron transport at complex III) caused increases in retrograde mitochondrial transport. Application of 2-deoxyglucose did not decrease transport compared with the mannitol control. To determine whether mitochondrial transport was correlated with mitochondrial potential, we stained the neurons with the mitochondrial potential-sensing dye JC-1. We found that ∼90% of mitochondria with high potential were transported towards the growth cone and ∼80% of mitochondria with low potential were transported towards the cell body. These experiments show for the first time that a uniform mitochondrial distribution is generated by local regulation of the stopping events of fast mitochondrial transport, and that the direction of mitochondrial transport is correlated with mitochondrial potential. These results have implications for axonal clogging, autophagy, apoptosis and Alzheimer's disease.

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The relation of axonal transport of mitochondria with microtubules and other axoplasmic organelles.

Cited by 44 publications

References 25 publications

Quantitative Ultrastructural Analysis of a Single Spinal Cord Demyelinated Lesion Predicts Total Lesion Load, Axonal Loss, and Neurological Dysfunction in a Murine Model of Multiple Sclerosis

Quantitative Ultrastructural Analysis of a Single Spinal Cord Demyelinated Lesion Predicts Total Lesion Load, Axonal Loss, and Neurological Dysfunction in a Murine Model of Multiple Sclerosis

Comparison of the temperature‐dependence of rapid axonal transport and microtubules in nerves of the rabbit and bullfrog.

Axonal mitochondrial transport and potential are correlated

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