The Fine Structure of the Axonal Torpedo in Purkinje Cells of the Human Cerebellum

Mann, David; Stamp, J.E.; Yates, P. O.; Bannister, Carys M.

doi:10.1080/01616412.1980.11739567

Cited by 24 publications

(21 citation statements)

References 8 publications

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“…Similar to what was observed at P11, NF+ torpedoes were also larger than NF- at P30 (NF+ length: 8.9 ± 0.3 μm; NF- length: 7.5 ± 0.6 μm; significantly different, P = 0.036; NF+ width: 4.7 ± 0.2 μm; NF- width: 3.5 ± 0.3 μm; significantly different, P = 0.003). These data raise the possibility that there may be functional subpopulations of developmental torpedoes, with the majority staining positive for neurofilament, and a significant minority that do not, in contrast to reports of disease-related torpedoes, where neurofilament accumulation in torpedoes is robust (Petito et al, 1973; Yagishita, 1978; Mann et al, 1980; Louis et al, 2009). An alternate explanation is that that the distinction between NF+ and NF- torpedoes is less distinct, with a continuum of neurofilament content in torpedoes ranging from low to high, rather than two separate populations.…”

Section: Resultsmentioning

confidence: 52%

“…These large presynaptic terminals bear a resemblance to Purkinje cell axonal torpedoes. Although ultrastructure analysis of disease-related Purkinje cell axonal torpedoes reveals that they do not contain vesicles (Petito et al, 1973; Yagishita, 1978; Mann et al, 1980; Louis et al, 2009), suggesting that they are not presynaptic release sites, we wondered whether developmental Purkinje cell axonal torpedoes might be the presynaptic structure of a transient synapse that functions during postnatal development. Interestingly, Purkinje cells form transient synapses onto other Purkinje cells during postnatal development (Watt et al, 2009), and transient synapses are thought to be a common feature of developing brain circuits (van Welie et al, 2011), and can also be found in other cerebellar neurons (Trigo et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

“…One striking feature of disease-related torpedoes that has been observed in several diseases is that they are enriched in disorganized neurofilament (Petito et al, 1973; Yagishita, 1978; Mann et al, 1980; Louis et al, 2009), which may be associated with alterations in axonal transport. We wondered whether developmental torpedoes also contained neurofilament.…”

Section: Resultsmentioning

confidence: 99%

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Transient Developmental Purkinje Cell Axonal Torpedoes in Healthy and Ataxic Mouse Cerebellum

Ljungberg

Lang-Ouellette

Yang

et al. 2016

Front. Cell. Neurosci.

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Information is carried out of the cerebellar cortical microcircuit via action potentials propagated along Purkinje cell axons. In several human neurodegenerative diseases, focal axonal swellings on Purkinje cells – known as torpedoes – have been associated with Purkinje cell loss. Interestingly, torpedoes are also reported to appear transiently during development in rat cerebellum. The function of Purkinje cell axonal torpedoes in health as well as in disease is poorly understood. We investigated the properties of developmental torpedoes in the postnatal mouse cerebellum of wild-type and transgenic mice. We found that Purkinje cell axonal torpedoes transiently appeared on axons of Purkinje neurons, with the largest number of torpedoes observed at postnatal day 11 (P11). This was after peak developmental apoptosis had occurred, when Purkinje cell counts in a lobule were static, suggesting that most developmental torpedoes appear on axons of neurons that persist into adulthood. We found that developmental torpedoes were not associated with a presynaptic GABAergic marker, indicating that they are not synapses. They were seldom found at axonal collateral branch points, and lacked microglia enrichment, suggesting that they are unlikely to be involved in axonal refinement. Interestingly, we found several differences between developmental torpedoes and disease-related torpedoes: developmental torpedoes occurred largely on myelinated axons, and were not associated with changes in basket cell innervation on their parent soma. Disease-related torpedoes are typically reported to contain neurofilament; while the majority of developmental torpedoes did as well, a fraction of smaller developmental torpedoes did not. These differences indicate that developmental torpedoes may not be functionally identical to disease-related torpedoes. To study this further, we used a mouse model of spinocerebellar ataxia type 6 (SCA6), and found elevated disease-related torpedo number at 2 years. However, we found normal levels of developmental torpedoes in these mice. Our findings suggest that the transient emergence of Purkinje cell axonal torpedoes during the second postnatal week in mice represents a normal morphological feature in the developing cerebellar microcircuit.

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Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Transient Developmental Purkinje Cell Axonal Torpedoes in Healthy and Ataxic Mouse Cerebellum

Ljungberg

Lang-Ouellette

Yang

et al. 2016

Front. Cell. Neurosci.

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“…Prominent among these changes is a substantial increase in the number of torpedoes [3]. Electron microscopic studies have revealed that these axonal swellings contain an excess and disorganization of neurofilaments [2, 39]. These accumulations, in general, can either be a cause or result of damaged axonal transport [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Torpedo Formation and Purkinje Cell Loss: Modeling their Relationship in Cerebellar Disease

et al. 2014

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Background Torpedo formation and Purkinje cell (PC) loss represent standard and inter-related cerebellar responses to injury. Surprisingly, the nature of their relationship has not been carefully characterized across a range of normal and disease states. Are brains with more torpedoes expected to have fewer PCs? We quantified torpedoes and PCs in four groups: essential tremor (ET), spinocerebellar ataxia (SCA), multiple system atrophy-cerebellar (MSA-C), and controls. Methods Brains from 100 individuals (58 ET, 27 controls, 7 SCA, 8 MSA-C) were available at the New York Brain Bank. After complete neuropathological assessment, a standard parasagittal neocerebellar block was harvested, a 7-μm thick section was stained with Luxol Fast Blue/Hematoxylin and Eosin, and torpedoes and PCs were quantified. Results For a given PC count, SCA and MSA-C cases often had higher torpedo counts than ET cases or controls. Furthermore, the relationship between torpedo and PC counts was complex. The correlation between torpedo and PC counts was negative in ET cases (i.e., individuals with more torpedoes had fewer PCs [i.e., more PC loss]) whereas the relationship was positive in MSA-C cases (i.e., individuals with fewer PCs [i.e., more PC loss] had fewer torpedoes). Patients with SCA showed both patterns. When all diagnostic groups were combined, the correlation was best fit by a quadratic (i.e. parabolic) model rather than a simple linear model; this model incorporated data on the negative correlation in ET cases, the mixed results in SCA cases, and the positive correlation in MSA-C cases (r = 0.636). Conclusions The relationship between torpedo and PC counts was complex and heterogeneous across a range of cerebellar disease states, and was best characterized by a quadratic rather than a simple model. With more severe cerebellar disease, torpedoes can be quite numerous, and are likely a common feature of surviving PCs, but eventually, dramatic loss of PC leads to a paradoxical reduction in observable torpedoes.

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“…Axonal torpedoes on Purkinje cells of the cerebellum have been observed at electron microscopic level in infantile neuroaxonal dystrophy, in two cases of brain tumours, and in a case of a 5-year-old boy suffering from juvenile astrocytoma [21,24,32]. The presence of intranuclear filamentous inclusions in cerebellar Golgi cells was reported by us in three patients with cerebellar tumours [4].…”

Section: Introductionmentioning

confidence: 97%

Ultrastructural pathology of human peritumoural oedematous cerebellar cortex

Castejón

2016

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The Fine Structure of the Axonal Torpedo in Purkinje Cells of the Human Cerebellum

Cited by 24 publications

References 8 publications

Transient Developmental Purkinje Cell Axonal Torpedoes in Healthy and Ataxic Mouse Cerebellum

Transient Developmental Purkinje Cell Axonal Torpedoes in Healthy and Ataxic Mouse Cerebellum

Torpedo Formation and Purkinje Cell Loss: Modeling their Relationship in Cerebellar Disease

Ultrastructural pathology of human peritumoural oedematous cerebellar cortex

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