Cerebellar Contributions to Motor Impairments in People with Multiple Sclerosis

Fietsam, Alexandra C.; Darling, Warren G.; Sosnoff, Jacob J.; Workman, Craig D.; Kamholz, John; Rudroff, Thorsten

doi:10.1007/s12311-021-01336-6

Cited by 5 publications

(4 citation statements)

References 117 publications

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“…While some of this atrophy may be due to white matter damage to thalamic tracts 131 , PTEs in thalamic neurons, which have also been seen in Parkinson's disease 65 , could play a part. Similarly, PTEs in cerebellar dentate neurons could contribute to the cerebellar atrophy and ataxia commonly found in MS 132 .…”

Section: Discussionmentioning

confidence: 99%

Potentially toxic elements in the brains of people with multiple sclerosis

Pamphlett

Buckland

Bishop

2023

Sci Rep

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Potentially toxic elements such as lead and aluminium have been proposed to play a role in the pathogenesis of multiple sclerosis (MS), since their neurotoxic mechanisms mimic many of the pathogenetic processes in MS. We therefore examined the distribution of several potentially toxic elements in the autopsied brains of people with and without MS, using two methods of elemental bio-imaging. Toxicants detected in the locus ceruleus were used as indicators of past exposures. Autometallography of paraffin sections from multiple brain regions of 21 MS patients and 109 controls detected inorganic mercury, silver, or bismuth in many locus ceruleus neurons of both groups, and in widespread blood vessels, oligodendrocytes, astrocytes, and neurons of four MS patients and one control. Laser ablation-inductively coupled plasma-mass spectrometry imaging of pons paraffin sections from all MS patients and 12 controls showed that combinations of iron, silver, lead, aluminium, mercury, nickel, and bismuth were present more often in the locus ceruleus of MS patients and were located predominantly in white matter tracts. Based on these results, we propose that metal toxicants in locus ceruleus neurons weaken the blood–brain barrier, enabling multiple interacting toxicants to pass through blood vessels and enter astrocytes and oligodendroglia, leading to demyelination.

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Section: Discussionmentioning

confidence: 99%

Potentially toxic elements in the brains of people with multiple sclerosis

Pamphlett

Buckland

Bishop

2023

Sci Rep

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“…The significance of this structure is evidenced by the fact that it contains over 50% of total brain neurons 19 , 43 and that its rate of size change over evolution in humans strongly correlates with that of the neocortex. 44 It consists of an inner WM core enveloped by a cortex, made up of three layers: 45 , 46 an internal granular layer, a Purkinje cell layer and an external molecular layer ( Figure 2 ). The granular layer is named after the small, granular in appearance and densely packed excitatory neurons that constitute the bulk of cells in this region.…”

Section: Cerebellar Disease In Multiple Sclerosismentioning

confidence: 99%

“…The output of the superior peduncle is almost exclusively efferent, while the middle peduncle is an entirely afferent pathway and the inferior peduncle contains both afferent and efferent pathways. 45 Projections into the cerebellum pass through the peduncles along mossy fibres originating from brainstem nuclei and the spinal cord and activating granular cells, or climbing fibres from the inferior olive activating Purkinje cells. Thus, information travels through the cerebellar WM to the cortex, is processed in the molecular layer and sent from the cortex to the DCN via the Purkinje layer before leaving the cerebellum via the superior and inferior peduncles.…”

Section: Cerebellar Disease In Multiple Sclerosismentioning

confidence: 99%

Cerebellar pathology in multiple sclerosis and experimental autoimmune encephalomyelitis: current status and future directions

Maxwell,

Orian

2023

J Cent Nerv Syst Dis

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Recent decades have witnessed significant progress in understanding mechanisms driving neurodegeneration and disease progression in multiple sclerosis (MS), but with a focus on the cerebrum. In contrast, there have been limited studies of cerebellar disease, despite the common occurrence of cerebellar symptoms in this disorder. These rare studies, however, highlight the early cerebellar involvement in disease development and an association between the early occurrence of cerebellar lesions and risk of worse prognosis. In parallel developments, it has become evident that far from being a region specialized in movement control, the cerebellum plays a crucial role in cognitive function, via circuitry connecting the cerebellum to association areas of the cerebrum. This complexity, coupled with challenges in imaging of the cerebellum have been major obstacles in the appreciation of the spatio-temporal evolution of cerebellar damage in MS and correlation with disability and progression. MS studies based on animal models have relied on an induced neuroinflammatory disease known as experimental autoimmune encephalomyelitis (EAE), in rodents and non-human primates (NHP). EAE has played a critical role in elucidating mechanisms underpinning tissue damage and been validated for the generation of proof-of-concept for cerebellar pathological processes relevant to MS. Additionally, rodent and NHP studies have formed the cornerstone of current knowledge of functional anatomy and cognitive processes. Here, we propose that improved insight into consequences of cerebellar damage in MS at the functional, cellular and molecular levels would be gained by more extensive characterization of EAE cerebellar pathology combined with the power of experimental paradigms in the field of cognition. Such combinatorial approaches would lead to improved potential for the development of MS sensitive markers and evaluation of candidate therapeutics.

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“…In addition, there are potential differences between remyelination by aged local OPCs vs. newly formed OPCs by NSCs, consistent with limited The nature and source of myelin regeneration in the adult cerebellum are still not clear, despite the description of cerebellar signs in people with MS as early as 1877 by Charcot. Cerebellar dysfunction, early in the MS disease course, is predictive of disability and disease progression, and most people with MS develop cerebellar signs after they enter the progressive stages [168][169][170][171][172]. Overall, 11-33% of people with MS are predominantly affected by cerebellar signs and symptoms, which include tremors, ataxia, and slurred speech, underscoring the importance of enhancing remyelination in the cerebellum [173,174].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Endogenous Neural Stem Cell Mediated Oligodendrogenesis in the Adult Mammalian Brain

Radecki

Samanta

2022

Cells

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Oligodendrogenesis is essential for replacing worn-out oligodendrocytes, promoting myelin plasticity, and for myelin repair following a demyelinating injury in the adult mammalian brain. Neural stem cells are an important source of oligodendrocytes in the adult brain; however, there are considerable differences in oligodendrogenesis from neural stem cells residing in different areas of the adult brain. Amongst the distinct niches containing neural stem cells, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are considered the principle areas of adult neurogenesis. In addition to these areas, radial glia-like cells, which are the precursors of neural stem cells, are found in the lining of the third ventricle, where they are called tanycytes, and in the cerebellum, where they are called Bergmann glia. In this review, we will describe the contribution and regulation of each of these niches in adult oligodendrogenesis.

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Cerebellar Contributions to Motor Impairments in People with Multiple Sclerosis

Cited by 5 publications

References 117 publications

Potentially toxic elements in the brains of people with multiple sclerosis

Potentially toxic elements in the brains of people with multiple sclerosis

Cerebellar pathology in multiple sclerosis and experimental autoimmune encephalomyelitis: current status and future directions

Endogenous Neural Stem Cell Mediated Oligodendrogenesis in the Adult Mammalian Brain

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