Age-related Changes in Tau Expression in Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Barańczyk‐Kuźma, Anna; Usarek, Ewa; Kuźma-Kozakiewcz, Magdalena; Kaźmierczak, Beata; Gajewska, Beata; Schwalenstöcker, Birgit; Ludolph, Albert C.

doi:10.1007/s11064-006-9242-4

Cited by 9 publications

(8 citation statements)

References 25 publications

(29 reference statements)

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“…However, growing evidence indicates the presence of functional changes in this structure in the course of ALS, including increased activations of areas involved in motor learning, among which basal ganglia and the cerebellum [38]. In our earlier studies of tau mRNA expressions in the cerebellum of SOD1G93A mice, we observed its very high increase at both presymptomatic and symptomatic stages, which was an opposite finding compared to the changes observed in the frontal cortex and spinal cord, the structures stereotypically involved in ALS pathogenesis [28,39]. It is possible that the kinesin expression is downregulated in response to increased tau expression.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The changes were prominent in frontal cortex, but not in hippocampus and spinal cord. In frontal cortex at symptomatic stage of the disease, the level of total tau mRNA was decreased by about 20%, mainly because of 2 N isoform down-regulation [26, 40]. In the present studies conducted on B6-C3H hybrids with the SOD1G93A mutation (SOD1/+) the total tau expression in frontal cortex at symptomatic stage was even lower (decreased by more than 60%) and the level of all isoforms was decreased, but especially that of 2 N (a threefold decrease).…”

Section: Discussionmentioning

confidence: 99%

“…The present results are with agreement with our earlier studies conducted on SOD1G93A mice (which were not hybrids with C3H). We have shown that the level of total tau-mRNA increases in cerebellum already in newborns (by 25%) and it further rises with age reaching the highest value at symptomatic stage (by 40%) due to enhance of all isoforms expression [40]. Cerebellum is the structure usually not studied in motor neuron diseases since cerebellar dysfunction is not a clinical feature of ALS.…”

Section: Discussionmentioning

confidence: 99%

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

et al. 2011

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Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions.

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“…In SOD1-G93A Tg mice model for ALS ( SOD1 G93A ). The most prominent alterations of tau expression were reported in the cerebellum (Baranczyk-Kuzma et al, 2007). …”

Section: Introductionmentioning

confidence: 99%

Overexpression of Human SOD1 Leads to Discrete Defects in the Cerebellar Architecture in the Mouse

et al. 2017

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The human superoxide dismutase 1 (SOD1) gene is responsible for neutralizing supercharged oxygen radicals within the cell. Mutation in SOD1 gene causes amyotrophic lateral sclerosis (ALS). Recent studies have shown involvement of the cerebellum in ALS, although the cerebellar contribution in SOD1 transgenic mice remains unclear. Using immunohistopathology, we investigated the Purkinje cell phenotype in the vermis of the SOD1 transgenic mice cerebellum. Calbindin 1 (Calb1) and three well-known zone and stripe markers, zebrin II, HSP25, and PLCβ4 have been used to explore possible alteration in zone and stripe. Here we show that Calb1 expression is significantly reduced in a subset of the Purkinje cells that is almost aligned with the cerebellar zones and stripes pattern. The Purkinje cells of SOD1 transgenic mice display a pattern of Calb1 down-regulation, which seems to proceed to Purkinje cell degeneration as the mice age. The onset of Calb1 down-regulation in Purkinje cells begins from the central zone and continues into the nodular zone, however it has not been observed in the anterior and posterior zones. In a subgroup of SOD1 transgenic mice in which gait unsteadiness was apparent, down-regulation of Calb1 is seen in a subset of PLCβ4+ Purkinje cells in the anterior zone. These observations suggest that the Calb1− subset of Purkinje cells in the anterior zone, which receives somatosensory input, causes unsteady gait. Our data suggest that human SOD1 overexpression leads to Calb1 down-regulation in the zone and strip pattern and raise the question of whether SOD1 overexpression leads to Purkinje cells degeneration.

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Age-related Changes in Tau Expression in Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Cited by 9 publications

References 25 publications

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

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

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Overexpression of Human SOD1 Leads to Discrete Defects in the Cerebellar Architecture in the Mouse

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