Clinical Utility of Skin Biopsy in Differentiating between Parkinson’s Disease and Multiple System Atrophy

Haga, Rie; Sugimoto, Kazuhiro; Nishijima, Haruo; Miki, Yasuo; Suzuki, Chieko; Wakabayashi, Keiji; Baba, Masayuki; Yagihashi, Soroku; Tomiyama, Masahiko

doi:10.1155/2015/167038

Cited by 34 publications

(35 citation statements)

References 27 publications

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“…PD is a progressive neurodegenerative disease whose main symptoms include bradykinesia, resting tremors and rigidity (16)(17)(18). In the present study, using an MPTP-induced mouse PD model, reduced motion bradykinesia, which is typical of PD, was apparent along with other symptoms of the disease.…”

Section: Discussionsupporting

confidence: 50%

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression

et al. 2016

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Abstract. The incidence rate of Parkinson's disease (PD) is ≤2% in Chinese individuals >65 years old, accounting for 40% of the global total of PD patients. The pathogenesis of PD is not yet clear, and oxidative stress-induced mitochondrial dysfunction is considered to be the main reason for the onset of PD. Studies have shown that matrine exhibits good antioxidant activity. Thus, the present study aimed to observe the protective effect and mechanism of matrine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuron damage. A total of 25 C57BL male mice were randomly divided into 5 groups, consisting of the control group (group A), the MPTP group (group B) and three matrine (4, 8 and 16 mg/kg) plus MPTP treatment groups (groups C, D and E, respectively). Results from a pole-climbing test and locomotor activity experiments were recorded. The mice were sacrificed 4 days later and brain dissection was performed. The levels of superoxide dismutase (SOD) and glutathione (GSH) were assessed. The expression level of tyrosine hydroxylase (TH) in the ventral midbrain was studied by immunofluorescence analysis. The expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) in the ventral midbrain was studied by western blot analysis. The experiments were repeated three times. Compared with control mice, the PD mice exhibited the typical behaviors associated with PD; matrine can alleviate this phenomenon, and with increasing matrine concentration, the symptoms were reduced significantly. Compared with the control mice, the PD mice had lower SOD and GSH activity, and matrine partially reversed the change in SOD and GSH activity. Immunofluorescence analysis showed that the level of TH in the ventral midbrain decreased significantly in the PD mice, and that the mice administered matrine showed higher expression of TH and levels of TH-positive cells. Western blotting results showed that the expression of Nrf2 in the ventral midbrain decreased significantly in the PD mice, and that matrine was able to reverse this phenomenon. In conclusion, by promoting antioxidant-related Nrf2 signaling pathways in the ventral midbrain, matrine can inhibit the oxidative damage of dopamine neurons in PD.

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Section: Discussionsupporting

confidence: 50%

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression

et al. 2016

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“…Unmyelinated and sparsely myelinated primary afferent Aδ and C fibers transfer thermal and noxious stimuli from all parts of the body to the central nervous system . A reduction in the density of intraepidermal unmyelinated nerve fibers (primary afferent sensory fibers) has been demonstrated in biopsied skin from patients with PD . These pain system lesions may account for pain syndromes reported in PD; approximately 30‐60% of such patients experience pain .…”

Section: Discussionsupporting

confidence: 91%

α‐Synuclein pathology in the cranial and spinal nerves in Lewy body disease

et al. 2015

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Accumulation of phosphorylated α-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated α-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that α-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA.

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“…Unlike our prior studies that included individuals with a clinically established diagnosis [3, 13], the present study included subjects that had both had a clinical diagnosis of PD as well as autopsy confirmation of disease stage. We note greater deposition of alpha-synuclein within pilomotor, sudomotor and vasomotor nerve fibers of tissue samples from subjects with Parkinson’s disease compared to control subjects using an antibody targeting multiple alpha-synuclein binding domains from amino acids 111-131.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous Alpha-Synuclein From Paraffin Embedded Autopsy Specimens in Parkinson’s Disease

Gibbons

Wang

Freeman

2017

JPD

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Background Parkinson disease (PD) is neurodegenerative disorder characterized by tremor, rigidity and bradykinesia and pathologically by the deposition of alpha-synuclein within different tissues. We, and others, have reported the detection of cutaneous alpha-synuclein in individuals with PD. Objective The goal of the present study was to detect alpha-synuclein deposition by immunohistochemical staining of skin samples in pathologically confirmed cases of PD. Methods Post-mortem skin biopsy samples from 11 individuals with PD, and 5 non-synucleinopathy control subjects were paraffin embedded and stained for total alpha-synuclein and protein gene product 9.5. Results Alpha-synuclein deposition was greater in both scalp and abdominal skin biopsy PD samples compared to control samples in pilomotor nerves (P<0.05), sudomotor nerves (P<0.05) and vasomotor nerves (P<0.05). Deposition of alpha-synuclein in scalp and abdominal tissue did not correlate with age, duration of PD, or severity of PD. Conclusions There is greater deposition of alpha-synuclein within pilomotor, sudomotor and vasomotor nerve fibers of paraffin embedded samples from autopsy confirmed cases of PD compared to control samples. However, assessment of alpha-synuclein deposition in post-mortem paraffin embedded tissue has many limitations and the utility of this technique in clinical and research studies is uncertain.

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Clinical Utility of Skin Biopsy in Differentiating between Parkinson’s Disease and Multiple System Atrophy

Cited by 34 publications

References 27 publications

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression

α‐Synuclein pathology in the cranial and spinal nerves in Lewy body disease

Cutaneous Alpha-Synuclein From Paraffin Embedded Autopsy Specimens in Parkinson’s Disease

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