scholarly journals Amelioration of L-DOPA-induced dyskinesia with vitamin D3 in Parkinsonian mice model

2021 ◽  
Author(s):  
Adedamola Bayo-Olugbami ◽  
Abdulrazaq Bidemi Nafiu ◽  
Abdulbasit Amin ◽  
Olalekan Michael Ogundele ◽  
Charles Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D3 ◽  
Microglial Activation ◽  
Cognitive Deficit ◽  
Mice Model ◽  
Abnormal Involuntary Movements ◽  
Methyl Transferase ◽  
Mao B ◽  
Receptor Modulation ◽  
Maximal Reduction

L-DOPA Induced Dyskinesia (LID) is associated with prolonged L-DOPA therapy. Vitamin-D receptor modulation improves motor-cognitive deficit in experimental LID Parkinsonism. Therefore, in this study, we investigated the mechanism underlying the anti-dyskinetic potential of Vitamin D3 (VD3). Dyskinesia was induced by chronic L-DOPA administration in 6-OHDA lesioned male C57BL6 mice. The experimental groups (Dyskinesia, Dyskinesia/VD3, and Dyskinesia/Amantadine) and controls were challenged with L-DOPA to determine the abnormal involuntary movements (AIMs) score during 14 days of VD3 (30 mg/kg) or Amantadine (40 mg/kg) treatment. Global behavioral Axial, Limb & Orolingual (ALO) AIMs were scored for 1 min at every 20 mins interval, over a duration of 100 mins on days 1,3,7,11 and 14 of treatment. Thereafter, brain samples were collected and processed for immunoblotting to assess striatal expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO), cathecol-o-methyl transferase (COMT), dopamine decarboxylase (DDC), CD11b, BAX, P47phox, and IL-1β. VD3 significantly attenuated ALO AIMs only on days 11 & 14, with maximal reduction of 32.7% compared with dyskinetic mice but had no effect on days 1, 3 & 7, while amantadine decreased AIMs all through days 1 to 14 with maximal reduction of 64.5%. TH and MAO-B expression were not significantly different across the groups. DDC was significantly suppressed in dyskinetic mice vs control (p<0.001) but remained unchanged in VD3 mice vs dyskinetic mice. COMT was upregulated in the dyskinetic group vs control (p<0.01) and attenuated in VD3 mice (p<0.05) compared to the dyskinetic group. Interestingly, VD3 inhibited significantly (p<0.01) oxidative stress (p47phox), apoptosis (BAX), inflammation (IL-1β), and microglial activation (CD11b) in dyskinetic mice. Overall, we find that the anti-dyskinetic effects of VD3 is associated with modulation of striatal oxidative stress, microglial responses, inflammation, and apoptotic signaling.

Targeting COVID-19 in Parkinson’s patients: Drugs repurposed.

2020 ◽  
Vol 27 ◽  
Author(s):  
Firoz Anwar ◽  
Salma Naqvi ◽  
Fahad A. Al-Abbasi ◽  
Nauroz Neelofar ◽  
Vikas Kumar ◽  
...  
Keyword(s):  
Day Treatment ◽  
Treatment Options ◽  
Developed Countries ◽  
Methyl Transferase ◽  
Comt Inhibitors ◽  
Mao B ◽  
Pharmacokinetic Properties ◽  
Us Fda ◽  
Approved Drugs ◽  
Fda Approved Drugs

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

Adenosine Receptor Modulation of Hypoxic-ischemic Injury in Striatum of Newborn Piglets

2020 ◽  
Vol 17 (4) ◽  
pp. 510-517
Author(s):  
Santiago Ortega-Gutierrez ◽  
Brandy Jones ◽  
Alan Mendez-Ruiz ◽  
Pankhil Shah ◽  
Michel T. Torbey
Keyword(s):  
Oxidative Stress ◽  
Atpase Activity ◽  
Neuronal Injury ◽  
Receptor Activation ◽  
Adult Mortality ◽  
Vehicle Group ◽  
Sodium Potassium ◽  
Receptor Modulation ◽  
A2a Receptor ◽  
Potassium Atpase

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of pediatric and adult mortality and morbidity. Unfortunately, to date, no effective treatment has been identified. In the striatum, neuronal injury is analogous to the cellular mechanism of necrosis observed during NMethyl- D-Aspartate (NMDA) excitotoxicity. Adenosine acts as a neuromodulator in the central nervous system, the role of which relies mostly on controlling excitatory glutamatergic synapses. Objective: To examine the effect of pretreatment of SCH58261, an adenosine 2A (A2A) receptor antagonist and modulator of NMDA receptor function, following hypoxic-ischemia (HI) on sodium- potassium ATPase (Na+, K+-ATPase) activity and oxidative stress. Methods: Piglets (4-7 days old) were subjected to 30 min hypoxia and 7 min of airway occlusion producing asphyxic cardiac arrest. Groups were divided into four categories: HI samples were divided into HI-vehicle group (n = 5) and HI-A2A group (n = 5). Sham controls were divided into Sham vehicle (n = 5) and Sham A2A (n = 5) groups. Vehicle groups were pretreated with 0.9% saline, whereas A2A animals were pretreated with SCH58261 10 min prior to intervention. Striatum samples were collected 3 h post-arrest. Sodium-potassium ATPase (Na+, K+-ATPase) activity, malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA) and glutathione (GSH) levels were compared. Results: Pretreatment with SCH58261 significantly attenuated the decrease in Na+, K+-ATPase, decreased MDA+4-HDA levels and increased GSH in the HI-A2A group when compared to HIvehicle. Conclusion: A2A receptor activation may contribute to neuronal injury in newborn striatum after HI in association with decreased Na+, K+-ATPase activity and increased oxidative stress.

scholarly journals Positive Modulation of PinkNelumbo nuciferaFlowers on Memory Impairment, Brain Damage, and Biochemical Profiles in Restraint Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Thawatchai Prabsattroo ◽  
Jintanaporn Wattanathorn ◽  
Pichet Somsapt ◽  
Opass Sritragool
Keyword(s):  
Oxidative Stress ◽  
Monoamine Oxidase ◽  
Spatial Memory ◽  
Brain Damage ◽  
Memory Deficit ◽  
Ki67 Expression ◽  
Mao B ◽  
Serum Corticosterone ◽  
Neuron Density ◽  
Oxidative Stress Status

Due to the crucial role of oxidative stress in the stress-induced memory deficit, the benefit of substance possessing antioxidant effect is focused. Since no data are available, we aimed to determine the effect ofNelumbo nuciferaflowers extract on spatial memory and hippocampal damage in stressed rats. Male Wistar rats, weighing 250–350 g, were orally givenN. nuciferaextract at doses of 10, 10, and 200 mg·kg−145 minutes before the exposure to 12-hour restraint stress. The spatial memory and serum corticosterone were assessed at 7 and 14 days of study period. At the end of study, acetylcholinesterase (AChE), monoamine oxidase type A and monoamine oxidase type B (MAO-A and MAO-B), oxidative stress status, neuron density, and Ki67 expression in hippocampus were also assessed. The results showed thatN. nuciferaextract decreased memory deficit and brain damage, serum corticosterone, oxidative stress status, AChE, and MAO-A and MAO-B activities but increased neuron density and Ki67 expression in hippocampus. These suggested that the improved oxidative stress status, adult neurogenesis, and cholinergic and monoaminergic functions might be responsible for the protective effect against stress-related brain damage and dysfunction of the extract. Therefore,N. nuciferaextract is the potential neuroprotective and memory enhancing agent. However, further researches are still required.

scholarly journals Association of Sympathovagal Imbalance with Cognitive Deficit, Insulin Resistance and Oxidative Stress in Newly Diagnosed Hypertension

2019 ◽  
Vol 5 (3) ◽  
pp. 145-150
Author(s):  
Subathra Thiruchengodu Ammaiyappan ◽  
Gopal Krushna Pal ◽  
Dhanalakshmi Yerrabelli ◽  
Pravati Pal ◽  
Nivedita Nanda
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cognitive Deficit ◽  
Newly Diagnosed ◽  
Sympathovagal Imbalance ◽  
And Oxidative Stress

scholarly journals Effects of a Single Oral Megadose of Vitamin D3 on Inflammation and Oxidative Stress Markers in Overweight and Obese Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

2021 ◽  
Vol Volume 14 ◽  
pp. 525-534
Author(s):  
Laine de Carvalho Guerra Pessoa Mamede ◽  
Rafaela Lira Formiga Cavalcanti de Lima ◽  
Alexandre Sérgio Silva ◽  
João Carlos Lima Rodrigues Pita ◽  
Nadjeanny Ingrid Galdino Gomes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trial ◽  
Vitamin D3 ◽  
Controlled Clinical Trial ◽  
Oxidative Stress Markers ◽  
Obese Women ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Stress Markers ◽  
And Oxidative Stress

scholarly journals MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress

2019 ◽  
Vol 2 (4) ◽  
pp. e201900308 ◽  
Author(s):  
Shun Nagashima ◽  
Keisuke Takeda ◽  
Nobuhiko Ohno ◽  
Satoshi Ishido ◽  
Motohide Aoki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Microglial Activation ◽  
Developmental Disorders ◽  
Inflammatory Diseases ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Three Dimensional ◽  
Abnormal Behavior ◽  
Mitochondrial Abnormalities

Mitochondrial abnormalities are associated with developmental disorders, although a causal relationship remains largely unknown. Here, we report that increased oxidative stress in neurons by deletion of mitochondrial ubiquitin ligase MITOL causes a potential neuroinflammation including aberrant astrogliosis and microglial activation, indicating that mitochondrial abnormalities might confer a risk for inflammatory diseases in brain such as psychiatric disorders. A role of MITOL in both mitochondrial dynamics and ER-mitochondria tethering prompted us to characterize three-dimensional structures of mitochondria in vivo. In MITOL-deficient neurons, we observed a significant reduction in the ER-mitochondria contact sites, which might lead to perturbation of phospholipids transfer, consequently reduce cardiolipin biogenesis. We also found that branched large mitochondria disappeared by deletion of MITOL. These morphological abnormalities of mitochondria resulted in enhanced oxidative stress in brain, which led to astrogliosis and microglial activation partly causing abnormal behavior. In conclusion, the reduced ER-mitochondria tethering and excessive mitochondrial fission may trigger neuroinflammation through oxidative stress.

scholarly journals Review on Parkinson’s Disease, a Neurodegenerative Disorder and The Role of Ceruloplasmin Protein in It

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Ajay Chaudhary ◽  
Noopur Khare ◽  
Yamini Dixit ◽  
Abhimanyu Kumar Jha
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Free Radical ◽  
Early Onset ◽  
Parenchymal Cell ◽  
Health Concern ◽  
Muscle Rigidity ◽  
Liver Parenchymal Cell ◽  
Mao B

Parkinson’s disease (PD), a neurodegenerative disease is becoming major health concern mainly for elder people of age over 60 years. The main cause of PD is permanent loss/death of dopaminergic nerve cells present in brain part called substantia nigra, which is responsible for dopamine synthesis. MAO-B, monoamine oxidase B, regulates dopamine metabolism and increased activity of MAO-B causes dopamine degradation which in turn promotes the accumulation of glutamate and oxidative stress with free radical liberation. Several factors like oxidative stress, free radical formation, increased cholesterol, mitochondrial dysfunction, nitric oxide toxicity, signal-mediated apoptosis, head trauma, and environmental toxins and gene mutations like VPS35, SNCA, EIF4G1, GBA, CHCHD, LRRK2, PINK1, DNAJC13 and SOD2 are associated with PD. Symptoms of PD include bradykinesia, muscle rigidity, resting tremors, postural instability and shuffling gait, constipation, sleep problems, fatigue, apathy, loss of smell and taste, excessive sweating, frequent nightmares, dream enacting behaviour, anxiety, depression, daytime drowsiness. In PD, low levels of ceruloplasmin were observed in people with early onset of PD. Ceruloplasmin, a ferroxidase enzyme which is synthesized in liver parenchymal cell, regulates iron metabolism and lower level of which causes iron accumulation in brain which is responsible for the early onset of PD. Levodopa-based preparations, Dopamine agonists, Catechol-o-methyltransferase (COMT) inhibitors, MOA-B inhibitors, Adjunctive therapy, Antiglutamatergics drugs are currently used for the treatment of PD.

scholarly journals PP2A Methylation is Necessary for Broad Stress Tolerance

2021 ◽  
Author(s):  
Maria T. Creighton ◽  
Dugassa Nemie-Feyissa ◽  
Nabeela Zaman ◽  
Sverre S. Johansen ◽  
Hege Dysjaland ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Tolerance ◽  
Dry Weight ◽  
Sodium Concentration ◽  
Post Translational Modification ◽  
Iron Starvation ◽  
Methyl Transferase ◽  
High Concentrations ◽  
Fe Homeostasis ◽  
Rock Wool

Abstract Background: LEUCINE CARBOXYL METHYL TRANSFERASE 1 (LCMT1) transfers a methyl group from the methyl donor S-adenosylmethionine (SAM) to the catalytic subunit of PROTEIN PHOSPHATASE 2A (PP2A). This post-translational modification of PP2A is manifested throughout eukaryotes from yeast to plants and animals. Although highly conserved, the importance of the methylation is poorly understood. Since Arabidopsis plants with knocked out LCMT1 grow and develop fairly normally, we decided to search for conditions that may reveal the benefits of this regulation. We compared the effects of various stressful conditions on Arabidopsis wild type (WT) and a lcmt1 mutant possessing only non-methylated PP2A. Results: Seedlings were grown in Petri dishes for 5-12 days, or in rock wool and soil for up to 7 weeks. A significant increase in sodium concentration was found for lcmt1 relative to WT, but this was not linked with stressful conditions. Plants were exposed to variable levels of the chelator EDTA, iron, zinc, aluminium, heat, and hydrogen peroxide. The lcmt1 mutant was clearly more sensitive than WT to all the various stresses, as demonstrated by effects on seedling root growth and on shoots of rosette stage plants on rock wool. When omitting EDTA, expression of genes known as signature genes for iron deficiency, FIT1, bHLH100, IMA1, IRT1 was strongly enhanced in lcmt1. Although an iron starvation response was induced, Fe homeostasis was apparently maintained by slowed growth in lcmt1 and the Fe level related to tissue dry weight was not changed. Among genes induced in lcmt1 were also the Zn induced gene ZIF1, and heat shock protein HSP90-1. Concentrations of non-iron transition metals, Cu, Mn and Zn, increased significantly in response to lack of EDTA for both lcmt1 and WT tissue, and especially the growth of lcmt1 was strongly hampered. Conclusions: Presence of the LCMT1 gene was necessary to cope efficiently with an imbalance in the micronutrients, heat stress, and oxidative stress. Methylation of PP2A appears important to ameliorate the toxic effects of metals present in unfavourable high concentrations as well as heat or oxidative stress. The experiments establish LCMT1 as a key component in broad stress tolerance.

Tardive Dyskinesia

1992 ◽  
Vol 160 (1) ◽  
pp. 110-112 ◽  
Author(s):  
Robertson Macpherson ◽  
Rachel Collis
Keyword(s):  
Cognitive Function ◽  
Tardive Dyskinesia ◽  
Psychiatric Hospital ◽  
Negative Symptoms ◽  
Cognitive Deficit ◽  
Defect State ◽  
Abnormal Involuntary Movements ◽  
Involuntary Movements ◽  
Short Test

Of 113 patients in long-stay wards of a psychiatric hospital, 43 had TD. Twenty-six of the 39 patients who consented to take part in the study were unaware of abnormal involuntary movements. These patients scored significantly lower on a short test of cognitive function than patients who were aware of such movements. The diagnosis of schizophrenia, perticularly the ‘defect’ state with cognitive deficit and negative symptoms, was found to be associated with lack of awareness of TD.

Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis

2021 ◽  
Author(s):  
Ji-Ren An ◽  
Jia-Nan Su ◽  
Gui-Yan Sun ◽  
Qing-Feng Wang ◽  
Ya-Dong Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Cognitive Deficit
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