Kinesin and cytoplasmic dynein in spinal spheroids with motor neuron disease

Toyoshima, Itaru; Sugawara, Masashiro; Kato, Kazumaro; Wada, Christopher A.; Hirota, Koichi; Hasegawa, Kazuko; Kowa, Hisayuki; Sheetz, Michael P.; Masamune, Osamu

doi:10.1016/s0022-510x(98)00137-3

Cited by 41 publications

(21 citation statements)

References 27 publications

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“…These morphological changes were observed at early and more frequently at late stages and could suggest early impairment in metabolite transport on NADPH-d positive interneurones. Proteins such as kinesin and cytoplasmic dynein, two major molecules responsible for axonal transport, are found in axon spheroids of chronic neurodegenerative disorders [40] and their accumulation in spheroids in motor neurone disease impairs fast axonal transport.…”

Section: Nadph-d In Prion Disease: Neuronal and Neuropil Changes In Nmentioning

confidence: 99%

Neuropil and neuronal changes in hippocampal NADPH‐diaphorase histochemistry in the ME7 model of murine prion disease

Boche

Gomes-Leal

Perry

et al. 2004

Neuropathology Appl Neurobio

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Nitric oxide (NO) has been implicated in neurotoxicity and cerebral blood flow changes in chronic neurodegeneration, but its activity in the mammalian prion diseases has not been studied in detail. Nicotine adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d) histochemistry is a simple and robust histochemical procedure that allows localization of the tissue distribution of NO synthases. The aim of the present study is to assess whether NADPH-d histochemical activity is altered in the hippocampus in the ME7 model of prion disease in C57BL/6J mice. At early and late stages after the initiation of the disease we assessed features of the NADPH-d positive cells and the neuropil histochemical activity in CA1 and dentate gyrus using densitometric analysis. In C57BL/6J mice 13 weeks postinjection of the prion agent ME7, when behavioural changes first become apparent, neuropil NADPH-d histochemical staining increases, whereas at late stages it decreases dramatically. Both type I and type II NADPH-d positive cells were found to survive throughout the hippocampal formation into the late stages of the disease, but diaphorase activity was reduced in dendritic branches and abnormal varicosities were present in both dendritic and axonal processes of NADPH-d positive type I cells. The pathophysiological implications of the results remain to be investigated but both blood flow alteration and NO neurotoxicity may be features of the disease.

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Section: Nadph-d In Prion Disease: Neuronal and Neuropil Changes In Nmentioning

confidence: 99%

Neuropil and neuronal changes in hippocampal NADPH‐diaphorase histochemistry in the ME7 model of murine prion disease

Boche

Gomes-Leal

Perry

et al. 2004

Neuropathology Appl Neurobio

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“…Interestingly, dynein was found to compete with kinesins for common places of attachment to microtubules [21]. Selective inhibition of the dynein or kinesin function resulted in a blockade of the axonal transport in both directions [22]. Immunohistochemical studies showed also an accumulation of kinesins in the spheroids found in axons of ALS patients [23].…”

Section: Introductionmentioning

confidence: 99%

Kinesin Expression in the Central Nervous System of Humans and Transgenic hSOD1G93A<b> </b>Mice with Amyotrophic Lateral Sclerosis

Kuźma‐Kozakiewicz

Chudy²,

Gajewska³

et al. 2012

Neurodegener Dis

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Background: Amyotrophic lateral sclerosis is a fatal motor neuron degenerative disease. Most cases are sporadic (SALS), and approximately 10% are familial (FALS) among which over 20% are linked to the SOD1 mutation. Both SALS and FALS have been associated with retrograde axonal transport defects. Kinesins (KIFs) are motor proteins involved mainly in anterograde transport; however, some also participate in retrograde transport. Objective: The purpose of the study was to investigate and compare the expression of kinesins involved in anterograde (KIF5A, 5C) and retrograde (KIFC3/C2) axonal transport in SALS in humans and FALS in mice with the hSOD1G93A mutation. Methods: The studies were conducted on various parts of the CNS from autopsy specimens of SALS patients, and transgenic mice at presymptomatic and symptomatic stages using real-time quantitative PCR and reverse-transcription PCR. Results: All KIF expression in the motor cortex of individual SALS subjects was higher than in the adjacent sensory cortex, in contrast to the expression in control brains. It was also significantly higher in the frontal cortex of symptomatic but not presymptomatic mice compared to wild-type controls. However, the mean KIF expression in the SALS motor and sensory cortexes was lower than in control cortexes. To a lesser extent the decrease in KIF mean expression also occurred in human but not in mouse ALS spinal cords and in both human and mouse cerebella. Conclusion: Disturbances in kinesin expression in the CNS may dysregulate both anterograde and retrograde axonal transports leading to motor neuron degeneration.

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“…Axonal transport is affected severely in neurological disorders (Goldstein, 2001a, b). Impairment of axonal transport has been long recognised in ALS patients (Breuer and Atkinson, 1988; Sasaki and Iwata, 1996), and kinesin has been found to accumulate in axonal swellings named spheroids (Toyashima et al, 1998). Defects in axonal transport have also been found in animal models for ALS (Collard et al, 1995; Warita et al, 1999), suggesting that alterations in the axonal transport machinery are important in the mechanism of selective motor neuronal death that occurs in motor neuron diseases.…”

Section: Discussionmentioning

confidence: 99%

Kif1Bβ isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis

Conforti

Dell'Agnello

Calvaresi

et al. 2002

J of Neuroscience Research

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The kinesin superfamily motor protein Kif1B is expressed in two isoforms, Kif1Balpha and Kif1Bbeta, with distinct cargo-binding domains. We examined the mRNA distribution of the two isoforms in adjacent sections of brain and spinal cord of adult mice using in situ hybridization analysis. Kif1Bbeta mRNA is enriched in several regions of brain and spinal cord. Its levels are four to five times higher than that of the alpha isoform, which was barely detectable. The highest mRNA levels of Kif1Bbeta were found in the cortex, hippocampus, cerebellum and the grey matter of the spinal cord. At the cellular level the highest signal was found in motor neurons in the motor nuclei of medulla oblongata and the ventral horn of spinal cord. Because expression of other Kif genes is altered in amyotrophic lateral sclerosis (ALS) models, we examined the expression level of Kif1Bbeta mRNA in the spinal cord of transgenic mice carrying the SOD1G93A mutation, a model of familial ALS, at presymptomatic and early stages of the disease. No changes were observed in Kif1Bbeta mRNA in motor neurons or in other regions of the spinal cord. These findings indicate that Kif1Balpha, which modulates the transport of mitochondria, may play a major role in tissues other than the central nervous system. Instead Kif1Bbeta, responsible for the transport of synaptic vesicle precursors, seems to play an important role in the nervous system, particularly in the lower motor neurons. The absence of changes of Kif1Bbeta mRNA in transgenic SOD1G93A mice suggests that other molecular mechanisms may play a role in the disruption of axonal transport occurring in the motor neurons of these mice.

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Kinesin and cytoplasmic dynein in spinal spheroids with motor neuron disease

Cited by 41 publications

References 27 publications

Neuropil and neuronal changes in hippocampal NADPH‐diaphorase histochemistry in the ME7 model of murine prion disease

Neuropil and neuronal changes in hippocampal NADPH‐diaphorase histochemistry in the ME7 model of murine prion disease

Kinesin Expression in the Central Nervous System of Humans and Transgenic hSOD1G93A<b> </b>Mice with Amyotrophic Lateral Sclerosis

Kif1Bβ isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis

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