Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease

Orimo, Satoshi; Uchihara, Toshiki; Kanazawa, Tohru; Itoh, Yoshinori; Wakabayashi, Keiji; Kakita, Akiyoshi; Takahashi, Hitoshi

doi:10.1111/j.1365-2990.2011.01194.x

Cited by 45 publications

(60 citation statements)

References 37 publications

(52 reference statements)

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“…SNc, locus coeruleus, raphe nuclei, pedunculopontine nucleus, DMV and nucleus basalis of Meynert neurons all have unusually long highly branched axons that are unmyelinated or thinly myelinated. 7,65 This feature is particularly well documented for SNc dopaminergic neurons. Single SNc axons terminating in the striatum are highly branched and possess as many as several hundred thousand synaptic release sites.…”

Section: Introductionmentioning

confidence: 97%

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The pathology roadmap in Parkinson disease

Surmeier¹,

Sulzer

2013

Prion

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Section: Introductionmentioning

confidence: 97%

“…This symptom has been attributed to a sympathetic denervation of the heart or vasculature. [5][6][7][8][9] In some PD and dementia with Lewy bodies patients, Lewy pathology is present in the peripheral vagal nerve and ganglia. 10,11 These axons originate in the DMV.…”

Section: Introductionmentioning

confidence: 99%

The pathology roadmap in Parkinson disease

Surmeier¹,

Sulzer

2013

Prion

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“…5 Lewy pathology has been documented in specific cortical layers (i.e., preferentially in deep layers of high-order sensory association areas). 5,6 Some previous imaging studies have demonstrated decreased cortical thickness in PD, 7,8 but reported results have been inconsistent and have not shown robust associations with disease progression in the absence of dementia. These inconsistencies may be attributable to several factors.…”

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confidence: 98%

“…We hypothesized that reductions in gyrification would follow the spatiotemporal distribution described in studies of Lewy pathology. 5,6 METHODS Longitudinal cohort participants. Patients with PD (n 5 70) and controls (n 5 70) with a Mini-Mental State Examination (MMSE) score $26 were selected from a large cohort study based on matching for baseline age distribution, sex ratio, and number of follow-up visits (table 1).…”

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confidence: 99%

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

et al. 2016

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Objective: Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity.Methods: Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, ,1 year [PD E , n 5 17], 1-5 years [PD M , n 5 19], .5 years [PD L , n 5 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n 5 87, control n 5 66) to validate our findings.Results: In the longitudinal cohort, PD L had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p , 0.05). Longitudinally, loss of gyrification was accelerated in PD M participants, compared to controls.LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample.Conclusions: Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo. In Parkinson disease (PD), degeneration of dopamine terminals is thought to progress rapidly within the first few years after diagnosis and then plateau.1 Thus, in more advanced stages of disease, non-nigrostriatal brain changes may serve as better markers of PD progression. Evidence suggests that widespread pathologic changes occur in the cortex, including apoptotic signaling, Lewy pathology, reduction in other neurotransmitters, and interneuron loss. [2][3][4] It is unclear, however, how cell death relates to the pattern of cortical Lewy pathology, and whether cortical changes can be used to gauge PD progression. 5 Lewy pathology has been documented in specific cortical layers (i.e., preferentially in deep layers of high-order sensory association areas). 5,6 Some previous imaging studies have demonstrated decreased cortical thickness in PD, 7,8 but reported results have been inconsistent and have not shown robust associations with disease progression in the absence of dementia. These

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“…One possible explanation for persistent autonomic neuropathy even after recovery of sensorimotor nerves is its high content rate of unmyelinated fibers. Unmyelinated axons and long or sparsely myelinated axons are more vulnerable to degeneration than thick myelinated axons 10. Therefore, degeneration of autonomic nerves might be more severe than that of sensorimotor nerves in this case.…”

Section: Discussionmentioning

confidence: 80%

Delayed autonomic neuropathy in a patient with diethylene glycol poisoning: a case report

Kamada

Suzuki

Yamamoto

et al. 2017

Acute Medicine & Surgery

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CaseA 72‐year‐old man presented to our hospital after ingesting insecticide containing approximately 2 mL/kg diethylene glycol, which exceeded the lethal dose of 1 mL/kg. The patient recovered from critical symptoms on acute phase until day 3, but received artificial ventilation for muscle weakness secondary to sensorimotor neuropathy on days 11–54.OutcomeEven after marked improvement from sensorimotor neuropathy, the patient continued to complain of orthostatic hypotension. Autonomic neuropathy was identified by positive result of a head‐up tilt test, and reduction in coefficient of variation of R‐R intervals and cardiac iodine‐123‐metaiodobenzylguanidine uptake for the assessment of cardiac sympathetic activity. The patient's symptoms fully recovered 2 years after the exposure to diethylene glycol.ConclusionThis case shows the first report of delayed autonomic neuropathy after recovery from severe sensorimotor neuropathy, and suggests the importance of continuous monitoring for late‐onset neurological complications.

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Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease

Abstract: These findings suggest that in PD unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve, because α-synuclein aggregates accumulate much more abundantly in unmyelinated axons.

Cited by 45 publications

References 37 publications

The pathology roadmap in Parkinson disease

The pathology roadmap in Parkinson disease

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

Delayed autonomic neuropathy in a patient with diethylene glycol poisoning: a case report

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