Identification of amyloidogenic proteins in the microbiomes of a rat Parkinson's disease model and wild‐type rats

2021 ◽  
Author(s):  
Line Friis Bakmann Christensen ◽  
Saeid Hadi Alijanvand ◽  
Michał Burdukiewicz ◽  
Florian‐Alexander Herbst ◽  
Henrik Kjeldal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Wild Type ◽  
Amyloidogenic Proteins

scholarly journals A locomotor assay reveals deficits in heterozygous Parkinson’s disease model and proprioceptive mutants in adult Drosophila

2019 ◽  
Vol 116 (49) ◽  
pp. 24830-24839 ◽  
Author(s):  
Aman Aggarwal ◽  
Heinrich Reichert ◽  
K. VijayRaghavan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Cost Effective ◽  
Fine Motor ◽  
Wild Type ◽  
Climbing Behavior ◽  
Locomotor Impairment ◽  
Locomotor Behaviors ◽  
Locomotor Disorders

Severe locomotor impairment is a common phenotype of neurodegenerative disorders such as Parkinson’s disease (PD). Drosophila models of PD, studied for more than a decade, have helped in understanding the interaction between various genetic factors, such as parkin and PINK1, in this disease. To characterize locomotor behavioral phenotypes for these genes, fly climbing assays have been widely used. While these simple current assays for locomotor defects in Drosophila mutants measure some locomotor phenotypes well, it is possible that detection of subtle changes in behavior is important to understand the manifestation of locomotor disorders. We introduce a climbing behavior assay which provides such fine-scale behavioral data and tests this proposition for the Drosophila model. We use this inexpensive, fully automated assay to quantitatively characterize the climbing behavior at high parametric resolution in 3 contexts. First, we characterize wild-type flies and uncover a hitherto unknown sexual dimorphism in climbing behavior. Second, we study climbing behavior of heterozygous mutants of genes implicated in the fly PD model and reveal previously unreported prominent locomotor defects in some of these heterozygous fly lines. Finally, we study locomotor defects in a homozygous proprioceptory mutation (Trp-γ1) known to affect fine motor control in Drosophila. Moreover, we identify aberrant geotactic behavior in Trp-γ1 mutants, thereby opening up a finer assay for geotaxis and its genetic basis. Our assay is therefore a cost-effective, general tool for measuring locomotor behaviors of wild-type and mutant flies in fine detail and can reveal subtle motor defects.

scholarly journals Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jui-Chih Chang ◽  
Yi-Chun Chao ◽  
Huei-Shin Chang ◽  
Yu-Ling Wu ◽  
Hui-Ju Chang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Olfactory Bulb ◽  
Disease Model ◽  
Intranasal Delivery ◽  
The Difference ◽  
And Migration ◽  
6 Hydroxydopamine ◽  
Locomotor Behaviors ◽  
Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

scholarly journals Observation of magnetic susceptibility changes within the thalamus: a comparative study between healthy and Parkinson’s disease afflicted cynomolgus monkeys using 7 T MRI

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sangwoo Kim ◽  
Youngjeon Lee ◽  
Chang-Yeop Jeon ◽  
Yeung Bae Jin ◽  
Sukhoon Oh ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Parkinson’S Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Disease Model ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Cynomolgus Monkeys ◽  
Positron Emission

Abstract Background Although the thalamus is known to modulate basal ganglia function related to motor control activity, the abnormal changes within the thalamus during distinct medical complications have been scarcely investigated. In order to explore the feasibility of assessing iron accumulation in the thalamus as an informative biomarker for Parkinson’s disease (PD), this study was designed to employ quantitative susceptibility mapping using a 7 T magnetic resonance imaging system in cynomolgus monkeys. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-injected cynomolgus monkey and a healthy control (HC) were examined by 7 T magnetic resonance imaging. Positron emission tomography with 18F-N-(3-fluoro propyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane was also employed to identify the relationship between iron deposits and dopamine depletion. All acquired values were averaged within the volume of interest of the nigrostriatal pathway. Findings Compared with the HC, the overall elevation of iron deposition within the thalamus in the Parkinson’s disease model (about 53.81% increase) was similar to that in the substantia nigra (54.81%) region. Substantial susceptibility changes were observed in the intralaminar part of the thalamus (about 70.78% increase). Additionally, we observed that in the Parkinson’s disease model, binding potential values obtained from positron emission tomography were considerably decreased in the thalamus (97.51%) and substantia nigra (92.48%). Conclusions The increased iron deposition in the thalamus showed negative correlation with dopaminergic activity in PD, supporting the idea that iron accumulation affects glutaminergic inputs and dopaminergic neurons. This investigation indicates that the remarkable susceptibility changes in the thalamus could be an initial major diagnostic biomarker for Parkinson’s disease-related motor symptoms.

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

scholarly journals Cytokinin Plant Hormones Have Neuroprotective Activity in In Vitro Models of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 361
Author(s):  
Gabriel Gonzalez ◽  
Jiří Grúz ◽  
Cosimo Walter D’Acunto ◽  
Petr Kaňovský ◽  
Miroslav Strnad
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Disease Model ◽  
Neuronal Cell ◽  
Zeatin Riboside ◽  
Neuroprotective Activity ◽  
Protective Activity

Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson’s disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, cis-zeatin riboside, and N6-isopentenyladenosine were active in the SAL-induced PD model. In addition, trans-, cis-zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.

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