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Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers.

ABSTRACT: The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA (n = 10) or saline solution (n = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.

SUBMITTER: Requejo C

PROVIDER: S-EPMC7591774 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers.

Requejo Catalina C López-de-Ipiña Karmele K López-de-Ipiña Karmele K Ruiz-Ortega José Ángel JÁ Fernández Elsa E Calvo Pilar M PM Morera-Herreras Teresa T Miguelez Cristina C Cardona-Grifoll Laura L Cepeda Hodei H Ugedo Luisa L Lafuente José Vicente JV

Frontiers in neuroscience 20201014

The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal inje ...[more]

PMID: 33154717

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Project description:BackgroundNocturnal symptoms in Parkinson's disease are often treated after management of daytime manifestations. In order to better understand the unmet needs of nocturnal symptoms management, we analyzed the characteristics and burden of nocturnal symptoms from patients' perspectives and explored their changes over time. Overall symptoms (occurring at day or night) were collected to compare whether the unmet needs related to nocturnal symptoms and to overall symptoms are different.MethodsWe used a Social Listening big-data technique to analyze large amounts of Parkinson's disease symptoms in dialogues available from social media platforms in 2016 to 2018. These symptoms were classified as either overall symptoms or nocturnal symptoms. We used share of voice (SOV) of symptoms as a proportion of total dialogues per year to reflect the characteristics of symptoms. Negative sentiment score of symptoms was analyzed to find out their related burden.ResultsWe found the SOV for overall motor symptoms was 79% and had not increased between 2016 and 2018 (79%, p = 0.5). The SOV for non-motor symptoms was 69% and had grown by 7% in 2018 (p < 0.01). The SOV for motor complications was 9% and had increased by 6% in 2018 (p < 0.01). The SOV of motor symptoms was larger than non-motor symptoms and motor complications (p < 0.01). The SOV of non-motor symptoms was larger than motor complications (p < 0.01). For nocturnal symptoms, 45% of the analyzed PD population reported nocturnal symptoms in 2018, growing by 6% (p < 0.01). The SOV for nocturnal-occurring motor symptoms was higher than most non-motor symptoms. However, non-motor symptoms had the higher increases and evoked higher negative sentiment regardless of whether they occurred during the day or night. For symptoms that can occur at either day or night, each nocturnal symptom was rated with a higher negative sentiment score than the same symptom during the day.ConclusionsThe growing SOV and the greater negative sentiment of nocturnal symptoms suggest management of nocturnal symptoms is an unmet need of patients. A greater emphasis on detecting and treating nocturnal symptoms with 24-h care is encouraged.

Project description:Background and aimsPlants with crassulacean acid metabolism (CAM) can be divided into two groups according to the major carbohydrates used for malic acid synthesis, either polysaccharide (starch) or monosaccharide (hexose). This is related to the mechanism and affects energy metabolism in the two groups. In Kalanchoë pinnata and K. daigremontiana, which utilize starch, ATP-dependent phosphofructokinase (tonoplast inorganic pyrophosphatase) activity is greater than inorganic pyrophosphate-dependent phosphofructokinase (tonoplast adenosine triphosphatase) activity, but the reverse is the case in pineapple (Ananas comosus) utilizing hexose. To test the hypothesis that the energy metabolism of the two groups differs, day-night changes in the contents of ATP, ADP, AMP, inorganic phosphate (Pi), phosphoenolpyruvate (PEP) and inorganic pyrophosphate (PPi) in K. pinnata and K. daigremontiana leaves and in pineapple chlorenchyma were analysed.MethodsThe contents of energy-rich compounds were measured spectrophotometrically in extracts of tissue sampled in the light and dark, using potted plants, kept for 15 d before the experiments in a growth chamber.Key resultsIn the three species, ATP content and adenylate energy charge (AEC) increased in the dark and decreased in the light, in contrast to ADP and AMP. Changes in ATP and AEC were greater in Kalanchoë leaves than in pineapple chlorenchyma. PPi content in the three species increased in the dark, but on illumination it decreased rapidly and substantially, remaining little changed through the rest of the light period. Pi content of Kalanchoë leaves did not change between dark and light, whereas Pi in pineapple chlorenchyma increased in the dark and decreased in the light, and the changes were far greater than in Kalanchoë leaves. Light-dark changes in PEP content in the three species were similar.ConclusionsThese results corroborate our hypothesis that day-night changes in the contents of energy-rich compounds differ between CAM species and are related to the carbohydrate used for malic acid synthesis.

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Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers.

Publications

Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers.

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