Kwang Deog Jo

1,25-Dyhydroxyvitamin D3 attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy

BACKGROUND AND OBJECTIVES Dysregulation of the autophagy pathway has been suggested as an important mechanism in the pathogenesis of Parkinsons disease (PD). Therefore, modulation of autophagy may be a novel strategy for the treatment of PD. Recently, an active form of vitamin D₃ has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D₃ (calcitriol) in an in vitro model of Parkinsons disease. METHODS An in vitro model of Parkinsons disease, the rotenone-induced neurotoxicity model in SH-SY5Y cells was adapted. We measured cell viability using an MTT assay, Annexin V/propidium iodide assay, and intracellular reactive oxygen species levels and analyzed autophagy-associated intracellular signaling proteins by Western blotting. RESULTS Rotenone treatment of SH-SY5Y cells reduced their viability. This treatment also increased reactive oxygen species levels and decreased levels of intracellular signaling proteins associated with cell survival; simultaneous exposure to calcitriol significantly reversed these effects. Additionally, calcitriol increased levels of autophagy markers, including LC3, beclin-1, and AMPK. Rotenone inhibited autophagy, as indicated by decreased beclin-1 levels and increased mTOR levels, and this effect was reversed by calcitriol treatment. DISCUSSION Calcitriol protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy signaling pathways such as those involving LC3 and beclin-1. These neuroprotective effects of calcitriol against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for its clinical use in the treatment of PD.

The Neuroprotective Effect of Erythropoietin on Rotenone-Induced Neurotoxicity in SH-SY5Y Cells Through the Induction of Autophagy.

Currently, the autophagy pathway is thought to be important for the pathogenesis of Parkinson’s disease (PD), and the modulation of autophagy may be a novel strategy for the treatment of this disease. Erythropoietin (EPO) has been reported to have neuroprotective effects through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms, and it has also been shown to modulate autophagy signaling in an oxygen toxicity model. Therefore, we investigated the effects of EPO on autophagy markers and evaluated its neuroprotective effect on rotenone-induced neurotoxicity. We adapted the rotenone-induced neurotoxicity model to SH-SY5Y cells as an in vitro model of PD. We measured cell viability using MTT and annexin V/propidium iodide assays and measured intracellular levels of reactive oxygen species. Immunofluorescence analysis was performed to measure the expression of LC3 and α-synuclein. Intracellular signaling proteins associated with autophagy were examined by immunoblot analysis. EPO mono-treatment increased the levels of mammalian target of rapamycin (mTOR)-independent/upstream autophagy markers, including Beclin-1, AMPK, and ULK-1. Rotenone treatment of SH-SY5Y cells reduced their viability, increased reactive oxygen species levels, and induced apoptosis and α-synuclein expression, and simultaneous exposure to EPO significantly reduced these effects. Rotenone enhanced mTOR expression and suppressed Beclin-1 expression, indicating suppression of the autophagy system. However, combined treatment with EPO restored Beclin-1 expression and decreased mTOR expression. EPO protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy-related signaling pathways. The experimental evidence for the EPO-induced neuroprotection against rotenone-induced dopaminergic neurotoxicity may significantly impact the development of future PD treatment strategies.

Biochemical protective effect of 1,25-dihydroxyvitamin D3 through autophagy induction in the MPTP mouse model of Parkinson's disease.

In our previous study, the neuroprotective effect of calcitriol was confirmed in SH-SY5Y cells. In this article, we explored whether calcitriol showed neuroprotection in a subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson’s disease. After mice were treated with MPTP alone or cotreated with MPTP and calcitriol, the substantia nigra pars compacta was dissected, and related protein levels were detected by western blot. Our results suggest that the MPTP-injected mice treated with calcitriol had attenuated tyrosine hydroxylase expression and increased LC3-II conversion compared with those that were not. Above all, calcitriol showed neuroprotection in the MPTP mouse model.

Central cholinergic dysfunction could be associated with oropharyngeal dysphagia in early Parkinson’s disease

Dysphagia is an important issue in the prognosis of Parkinson’s disease (PD). Although several studies have reported that oropharyngeal dysphagia may be associated with cognitive dysfunction, the exact relationship between cortical function and swallowing function in PD patients is unclear. Therefore, we investigated the association between an electrophysiological marker of central cholinergic function, which reflected cognitive function, and swallowing function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the enrolled patients into two groups: PD with dysphagia and PD without dysphagia. The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of the dysphagia. To assess central cholinergic dysfunction, short latency afferent inhibition (SAI) was evaluated. We analyzed the relationship between central cholinergic dysfunction and oropharyngeal dysphagia and investigated the characteristics of the dysphagia. The SAI values were significantly different between the two groups. The comparison of each VFSS component between the PD with dysphagia group and the PD without dysphagia group showed statistical significance for most of the oral phase components and for a single pharyngeal phase component. The total score on the VDS was higher in the PD with dysphagia group than in the PD without dysphagia group. The Mini-Mental State Examination and SAI values showed significant correlations with the total score of the oral phase components. According to binary logistic regression analysis, SAI value independently contributed to the presence of dysphagia in PD patients. Our findings suggest that cholinergic dysfunction is associated with dysphagia in early PD and that an abnormal SAI value is a good biomarker for predicting the risk of dysphagia in PD patients.

Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease.

Background and Objectives: Gastrointestinal dysfunction is a common non motor symptom in Parkinsons disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying. Methods: Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T1/2) was determined. The PD patients were divided into a delayed-GET group and a normal-GET group. Results: The serum 25-hydroxyvitamin D3 levels were decreased in the delayed-GET group compared with the normal-GET and control groups (11.59 ± 4.90 vs. 19.43 ± 6.91 and 32.69 ± 4.93, respectively, p < 0.01). In the multivariate model, the serum 25-hydroxyvitamin D3 level was independently associated with delayed gastric emptying in PD patients. Conclusions: Vitamin D status may be an independent factor for gastric dysmotility in PD. Although the underlying mechanism remains to be characterized, vitamin D status may play a role in the pathogenesis of delayed gastric emptying in drug-naive PD.

Persistent negative visual aura in migraine without headache: a case report

IntroductionPersistent migraine aura without headache is an extremely rare condition. The International Headache Society defines various subtypes of migraines, including “persistent migraine aura without infarction” and “typical aura without headache.”Case presentationWe describe the case of a 21-year-old Asian woman with a history of migraine without aura who had (as her first aura episode) persistent negative visual symptoms without headache for 6 months. We detected no lesions that could cause her persistent visual symptoms. Based on the patient’s history of migraine without aura and responsiveness to furosemide and lamotrigine, we concluded that the visual symptoms in this case were related to migraine visual auras.ConclusionsPersistent visual aura without headache overlapped the criteria for the two migraine subtypes mentioned above and thus did not fit an exact diagnosis. Therefore, we assert that new criteria are needed to encompass uncertain visual symptoms of migraine aura.

Triple stimulation technique findings in vascular Parkinsonism and Parkinson's disease.

OBJECTIVE One of the predominant clinical features that differentiates vascular Parkinsonism (VP) from Parkinsons disease (PD) is the pyramidal sign. The triple stimulation technique (TST) is one of the most sensitive methods for comparing upper motor neuron involvement in patients with VP and PD. This study aimed to evaluate the usefulness of the TST as a diagnostic tool for VP. METHODS Thirteen VP patients, 18 PD patients and 10 age-matched healthy controls were enrolled in this study. We obtained basic participant demographic information and transcranial magnetic stimulation (TMS) parameters, including the TST amplitude ratio, from all participants. We compared the TMS parameters among the VP, PD and control groups. RESULTS The TST amplitude ratio was significantly lower in the VP group than in the PD and control groups (71.59 ± 11.86 vs. 96.42 ± 5.11 and 97.70 ± 3.82, respectively; p<0.01). The TST amplitude ratio was positively correlated with scores obtained on the United Parkinsons Disease Rating Scale-III, which reflects motor function. CONCLUSIONS The TST is an effective and easy technique that offers improved diagnostic sensitivity in patients with VP by assessing upper motor neuron involvement. The TST may also represent a useful monitoring tool for evaluating disease progression. SIGNIFICANCE This study is the first to assess pyramidal involvement in patients with VP using the collision technique.

P35-6 Quantitative assessment of cerebral hemodynamics in a adult moyamoya disease: evaluation with acetazolamide challenged perfusion CT and SPECT imaging

with ischemic lesions. Differences in mean GTE were analyzed using non parametric test. Results: Although group 3 shows higher mean GET score (4.57) than group 1 (3.33) and 2 (2.50), this do not met statistical significant differences (p = 0.05). Conclusions: The GTE score is a simple EEG scoring method that could be helpful in the screening of silent cerebrovascular damage of hypertensive patients. Future investigations should be done to explore the influence of covariates.

P35-7 Cerebral hemodynamics in patients with moyamoya syndrome associated with atherosclerotic occlusion of the middle cerebral arteries

with ischemic lesions. Differences in mean GTE were analyzed using non parametric test. Results: Although group 3 shows higher mean GET score (4.57) than group 1 (3.33) and 2 (2.50), this do not met statistical significant differences (p = 0.05). Conclusions: The GTE score is a simple EEG scoring method that could be helpful in the screening of silent cerebrovascular damage of hypertensive patients. Future investigations should be done to explore the influence of covariates.

PO15.24 Cerebral Hemodynamics in Patients with Symptomatic Bilateral Carotid Occlusion: Evaluation with CT Perfusion Imaging

with PFO had significantly fewer risk factors than patients without PFO (1.45 vs. 2.07; P= .006). Embolic infarct pattern was determined by DWI and MR angiography of the patient and observed more frequently in the patient without PFO than patient with PFO (52.4 vs. 21.4%; P= .006). There is no significant difference between patients with and without PFO in the prevalence of intraand extracranial arterial stenosis/occlusion (38.3 vs. 48.8%; P= .395). The degree of RLS correlate with neither the embolic infarct pattern (P= .101) nor arterial stenosis/occlusion (p = .496). Conclusions: These results consolidate the fact that PFO is an important risk factor for the young stroke patients. However, the infarct patterns of PFO patients were not compatible with embolic mechanism, and amount of RLS in PFO also did not correlate with the embolic infarct pattern. Mechanism other than the embolism might contribute to the ischemic stroke in these patients.