The Effect of Levosimendan on Two Distinct Rodent Models of Parkinson’s Disease

2020 ◽  
Vol 17 ◽  
Author(s):  
Amjad N. Abu Irmaileh ◽  
Karem H. Alzoubi ◽  
Abeer M Rababah
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Direct Injection ◽  
Challenge Test ◽  
Phosphodiesterase Inhibitor ◽  
Intracerebral Injection ◽  
Clinical Value ◽  
6 Hydroxydopamine ◽  
Calcium Sensitizer

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterized by motor symptoms related to the deficiency in dopamine levels, and cognitive symptoms that are similar in nature to those manifested during Alzheimer’s disease. Levosimendan, on the other hand, is a calcium sensitizer and phosphodiesterase inhibitor that was shown to possess neuroprotective, memory-enhancing, and anti-apoptotic properties. Objective: In the current study, the possible protective effect of levosimendan was investigated in two animal models of Parkinson’s disease. Methods: Both intracerebral injection 6-hydroxydopamine (6-OHDA) and the direct injection of lipopolysaccharide (LPS) into the substantia nigra were used as models to induce Parkinson’s-like behavior. Levosimendan (12 µg/kg intraperitoneally once weekly) was started 7 days before or 2 days after lesioning of the animals. At day 14 post-lesioning, animals were subjected to apomorphine challenge, which was correlated with dopamine levels in the striatum and tyrosine hydroxylase (TH)-positive nigral cells. Results: Results showed that levosimendan restored the number of rotations in the apomorphine challenge test, the levels of dopamine in the striatum, and the TH-positive nigral cells when administered 7 days before, but not two days after 6-OHDA lesioning. In the LPS model of PD, the number of rotations in the apomorphine challenge test, the levels of dopamine in the striatum, and the TH-positive nigral cells were restored when levosimendan was administered 7 days before as well as two days after lesioning. Conclusion: Levosimendan seems to provide a promising agent with potential clinical value for PD.

The beneficial effect of vanillin on 6-hydroxydopamine rat model of Parkinson’s disease

2020 ◽  
Vol 38 (5) ◽  
pp. 369-373
Author(s):  
Rasha Abuthawabeh ◽  
Amjad N. Abuirmeileh ◽  
Karem H. Alzoubi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Beneficial Effect ◽  
Wistar Rats ◽  
Neurodegenerative Disorder ◽  
Striatal Dopamine ◽  
Intracerebral Injection ◽  
Protective Properties ◽  
Male Wistar Rats ◽  
6 Hydroxydopamine

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is related to neuroinflammation. Vanillin, which possesses both antioxidant, and anti-inflammatory properties, can be a candidate for neuroprotection in PD. Objective: This study was aimed to investigate the effects of vanillin on the 6-hydroxydopamine (6-OHDA) rodent model of PD. Methods: Male Wistar rats were administrated intraperitoneal (i.p) or oral vanillin at a dose of 20 mg/kg/day for 7 days that was started at three days before or seven days after intracerebral injection of 6-OHDA. The 6-OHDA-induced lesions were assessed behaviorally using the apomorphine rotation test, neurochemically via measuring striatal dopamine concentrations, and through immunohistochemistry. Results: Both oral and IP vanillin at three days before or seven days after 6-OHDA lesioning exhbited significantly lower tight contralateral rotations upon apomorphine challenge, and higher striatal dopamine concentrations. Conclusions: Vanillin seems to offer protective properties against 6-OHDA lesion via preserving striatal dopamine levels.

scholarly journals Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

2015 ◽  
Vol 51 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Débora Dalla Vecchia ◽  
Marissa Giovanna Schamne ◽  
Marcelo Machado Ferro ◽  
Ana Flávia Chaves dos Santos ◽  
Camila Lupepsa Latyki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Hypericum Perforatum ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Turning Behavior ◽  
Age Related ◽  
Lesion Side ◽  
6 Hydroxydopamine

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

scholarly journals EXPERIMENTAL ANIMAL MODELS OF PARKINSON’S DISEASE: AN OVERVIEW

2020 ◽  
pp. 12-17
Author(s):  
MOHD IMRAN ◽  
ANURADHA MISHRA ◽  
AFREEN USMANI ◽  
ASIF EQBAL
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Current Treatment ◽  
Review Article ◽  
Transgenic Models ◽  
Slowing Down ◽  
Gradual Loss ◽  
Gait Dysfunction ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the 2nd most common neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra in the midbrain which leads to motor symptoms: For instance, gait dysfunction, involuntary tremor, rigidity, and progressive postural instability. PD has no cure and available current treatment is only symptomatic. At present, the main treatment of PD relies on Levodopa that slowing down the disease development to some level but can lead to several side effects. The literature confirms the available models of Parkinsonism that is chemical-induced, that is, by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine-induced Parkinsonism furthermore transgenic models linked to monogenic alterations in SNCA, LRRK2, UCH-L1, PRKN, and PINK1 genes. In this review article, we conclude that the presently available neurotoxic models of PD that offer a platform for neuroprotective drug discovery.

scholarly journals Heterogeneity of Incipient Atrophy Patterns in Parkinson’s Disease

2018 ◽  
Author(s):  
Pedro D. Maia ◽  
Sneha Pandya ◽  
Justin Torok ◽  
Ajay Gupta ◽  
Yashar Zeighami ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
High Variability ◽  
Clinical Value ◽  
Optimization Routine ◽  
Penalized Optimization ◽  
The Brain

AbstractParkinson’s Disease (PD) is a the second most common neurodegenerative disorder after Alzheimer’s disease and is characterized by cell death in the amygdala and in substructures of the basal ganglia such as the substantia nigra. Since neuronal loss in PD leads to measurable atrophy patterns in the brain, there is clinical value in understanding where exactly the pathology emerges in each patient and how incipient atrophy relates to the future spread of disease. A recent seed-inference algorithm combining an established network-diffusion model with an L1-penalized optimization routine led to new insights regarding the non-stereotypical origins of Alzheimer’s pathologies across individual subjects. Here, we leverage the same technique to PD patients, demonstrating that the high variability in their atrophy patterns also translates into heterogeneous seed locations. Our individualized seeds are significantly more predictive of future atrophy than a single seed placed at the substantia nigra or the amygdala. We also found a clear distinction in seeding patterns between two PD subgroups – one characterized by predominant involvement of brainstem and ventral nuclei, and the other by more widespread frontal and striatal cortices. This might be indicative of two distinct etiological mechanisms operative in PD. Ultimately, our methods demonstrate that the early stages of the disease may exhibit incipient atrophy patterns that are more complex and variable than generally appreciated.

scholarly journals EFFECT OF SESAMOL IN ASSOCIATION WITH FOLIC ACID ON 6-OHDA INDUCED PARKINSONIAN ANIMALS- BIOCHEMICAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL EVIDENCE

2017 ◽  
Vol 10 (4) ◽  
pp. 46 ◽  
Author(s):  
Khadira Sereen ◽  
Vijayalakshmi K ◽  
Priya Nagappan ◽  
Shinu Balima
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Folic Acid ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Biochemical Parameter ◽  
Lesion Group ◽  
Control Group ◽  
Tbars Level ◽  
6 Hydroxydopamine

Objective: Parkinson’s disease (PD) is the world’s second neurodegenerative disorder. Degeneration of dopaminergic neurons is the hallmark of the disease. Here is a novel approach to treat PD with a phenolic compound Sesamol (SA) and in combination with Folic acid (FA).Methods: The study was designed with five groups of animals and 6 rats in each group. The rats was infused with 6-hydroxydopamine (10μg/2μl in 0.1% ascorbic acid saline) once for the development of PD, Group 1(control), Group 2(Lesion), Group 3(Lesion+ SA), Group 4(Lesion + SA+ FA) and Group 5(Lesion+ L-dopa). The biochemical parameter like glucose, triglycerides, protein, folic acid, TBARS and antioxidant profile in serum were estimated. The neurotransmitters level in striatum was estimated and histopathology of striatum and mid-brain tissues was carried out.Results: The results showed that 6-hydroxydopamine induced lesion has a significant alteration in the level of glucose, triglycerides, protein and folic acid where as TBARS level was elevated and the activities of antioxidants and neurotransmitters level were reduced. This was significantly restored on SA+FA treatment. The lesion group shows an abnormal architecture of striatum and mid-brain, whereas on SA+FA treatment there was minimal abnormality.Conclusion: Thus our study demonstrates that Sesamol has neuroprotective effect against 6-hydroxy dopamine insult and showed a synergic effect when combined with Folic acid.Keywords: Parkinson’s disease, Sesamol, Folic acid, 6-Hydroxy dopamine, Neurotransmitter, Antioxidant

scholarly journals Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson’s Disease In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hefeng Zhou ◽  
Min Shao ◽  
Xuanjun Yang ◽  
Chuwen Li ◽  
Guozhen Cui ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Coordination ◽  
Neurodegenerative Disorder ◽  
Nerve Fibers ◽  
Substantia Nigra Pars Compacta ◽  
Neuroprotective Effects ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and there is no cure for it at present. We have previously reported that the tetramethylpyrazine (TMP) derivative T-006 exhibited beneficial effects in Alzheimer’s disease (AD) models. However, its effect on PD remains unclear. In the present study, we investigated the neuroprotective effects and underlying mechanisms of T-006 against 6-hydroxydopamine- (6-OHDA-) induced lesions in in vivo and in vitro PD models. Our results demonstrated that T-006 alleviated mitochondrial membrane potential loss and restored the energy metabolism and mitochondrial biogenesis that were induced by 6-OHDA in PC12 cells. In addition, animal experiments showed that administration of T-006 significantly attenuated the 6-OHDA-induced loss of tyrosine hydroxylase- (TH-) positive neurons in the SNpc, as well as dopaminergic nerve fibers in the striatum, and also increased the concentration of dopamine and its metabolites (DOPAC, HVA) in the striatum. Functional deficits were restored following T-006 treatment in 6-OHDA-lesioned mice, as demonstrated by improved motor coordination and rotational behavior. In addition, we found that the neuroprotective effects of T-006 were mediated, at least in part, by the activation of both the PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM pathways. In summary, our findings demonstrate that T-006 could be developed as a novel neuroprotective agent for PD, and the two pathways might be promising therapeutic targets for PD.

scholarly journals Baicalein Mediates Mitochondrial Autophagy via miR-30b and the NIX/BNIP3 Signaling Pathway in Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Min Chen ◽  
Li Peng ◽  
Ping Gong ◽  
Xiaoli Zheng ◽  
Tao Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Membrane Potential ◽  
Mitochondrial Membrane ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Protein Levels ◽  
Neurological Score ◽  
6 Hydroxydopamine ◽  
Related Proteins

Parkinson’s disease (PD) is regarded as a severe neurodegenerative disorder. Baicalein is involved in the treatment of PD. This study explored the mechanism of baicalein in PD. The PD rat model was established using 6-hydroxydopamine. The neurologic score, dopamine (DA) content, apoptotic cells, and neuronal damage were evaluated after rats were treated with baicalein. Autophagy in PD rats was inhibited using 3-methyladenine (3-MA). The mitochondrial membrane potential (MMP) and autophagy-related proteins (LC3, P62) were detected. Next, agomiR-30b was transfected into PD rats. The targeting relation between miR-30b and NIX was predicted and verified. Then, sh-NIX was transfected into PD rats, and the effects of miR-30b and NIX on MMP, LC3, and P62 were assessed. When miR-30b was overexpressed using agomiR-30b, the NIX and BNIP3 levels were detected. Baicalein increased the neurological score and restored DA content, neurons, MMP, and mitochondrial autophagy protein levels. Baicalein inhibited miR-30b expression and miR-30b targeted NIX. miR-30b upregulation or NIX silencing reversed the effect of baicalein on MMP and mitochondrial autophagy. Baicalein upregulated NIX and BNIP3 expressions, while miR-30b overexpression inhibited NIX and BNIP3 expressions. In summary, baicalein mediated mitochondrial autophagy and restored neuronal activity by downregulating miR-30b and activating the NIX/BNIP3 pathway, thus protecting against PD.

Early Expression of Neuronal Dopaminergic Markers in a Parkinson’s Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs)

2020 ◽  
Vol 19 (2) ◽  
pp. 148-162
Author(s):  
Carmen Parra-Cid ◽  
Eduardo Orozco-Castillo ◽  
Julieta García-López ◽  
Elena Contreras-Figueroa ◽  
Laura E. Ramos-Languren ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Disease Model ◽  
Brain Regions ◽  
Substantia Nigra Pars Compacta ◽  
Adult Rats ◽  
Promising Alternative ◽  
Therapeutic Modalities ◽  
6 Hydroxydopamine

Background: Parkinson’s Disease (PD) is a common neurodegenerative disorder affecting the dopaminergic (DAergic) system. Replacement therapy is a promising alternative aimed at reconstructing the cytoarchitecture of affected brain regions in PD. Experimental approaches, such as the replacement of DAergic neurons with cells obtained from the Enteric Nervous System (ENS) has yet to be explored. Objective: To establish and characterize a cell replacement strategy with ENS Cells (ENSCs) in a PD model in rats. Methods: Since ENSCs can develop mature DAergic phenotypes, here we cultured undifferentiated cells from the myenteric plexus of newborn rats, establishing that they exhibit multipotential characteristics. These cells were characterized and further implanted in the Substantia nigra pars compacta (SNpc) of adult rats previously lesioned by a retrograde degenerative model produced by intrastriatal injection of 6-Hydroxydopamine (6-OHDA). DAergic markers were assessed in implants to validate their viability and possible differentiation once implanted. Results: Cell cultures were viable, exhibited stem cell features and remained partially undifferentiated until the time of implant. The retrograde lesion induced by 6-OHDA produced DAergic denervation, reducing the number of fibers and cells in the SNpc. Implantation of ENSCs in the SNpc of 6-OHDAlesioned rats was tracked after 5 and 10 days post-implant. During that time, the implant increased selective neuronal and DAergic markers, Including Microtubule-Associated Protein 2 (MAP-2), Dopamine Transporter (DAT), and Tyrosine Hydroxylase (TH). Conclusion: Our novel results suggest that ENSCs possess a differentiating, proliferative and restorative potential that may offer therapeutic modalities to attenuate neurodegenerative events with the inherent demise of DAergic neurons.

scholarly journals Neuroprotective and Symptomatic Effects of Cannabidiol in an Animal Model of Parkinson’s Disease

2021 ◽  
Vol 22 (16) ◽  
pp. 8920
Author(s):  
Claudio Giuliano ◽  
Miriam Francavilla ◽  
Gerardo Ongari ◽  
Alessandro Petese ◽  
Cristina Ghezzi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Neurodegenerative Disorder ◽  
Receptor Potential ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Transient Receptor Potential Vanilloid ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta, leading to classical PD motor symptoms. Current therapies are purely symptomatic and do not modify disease progression. Cannabidiol (CBD), one of the main phytocannabinoids identified in Cannabis Sativa, which exhibits a large spectrum of therapeutic properties, including anti-inflammatory and antioxidant effects, suggesting its potential as disease-modifying agent for PD. The aim of this study was to evaluate the effects of chronic treatment with CBD (10 mg/kg, i.p.) on PD-associated neurodegenerative and neuroinflammatory processes, and motor deficits in the 6-hydroxydopamine model. Moreover, we investigated the potential mechanisms by which CBD exerted its effects in this model. CBD-treated animals showed a reduction of nigrostriatal degeneration accompanied by a damping of the neuroinflammatory response and an improvement of motor performance. In particular, CBD exhibits a preferential action on astrocytes and activates the astrocytic transient receptor potential vanilloid 1 (TRPV1), thus, enhancing the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). These results overall support the potential therapeutic utility of CBD in PD, as both neuroprotective and symptomatic agent.

scholarly journals Neuroprotective Effect of Intrastriatal Caffeic Acid Phenethyl Ester Treatment in 6-OH Dopamine Model of Parkinson’s Disease in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Burak Cem Soner ◽  
Eda Acikgoz ◽  
Salim Yalcin Inan ◽  
Sule Ayla ◽  
Ayse Saide Sahin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caffeic Acid ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Caffeic Acid Phenethyl Ester ◽  
Adhesive Tape ◽  
Behavioral Studies ◽  
Male Wistar Rats ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and the main cause of PD is still not known. Until now, no cure for Parkinson’s disease is yet in sight. Caffeic acid phenethyl ester (CAPE) is a polyphenolic component of the propolis, which can be derived from honeybee hive propolis. We aimed to determine the effect of intrastriatal CAPE administration as a neuroprotective agent on 6-hydroxydopamine (6-OHDA)-induced PD model. Adult male Wistar rats weighing 280–320 g were used. The PD model was induced with unilateral intrastriatal 6-OHDA injection. Treatment groups received 20 μmol/5 μL/4 day and 80 μmol/5 μL/4 day CAPE 24 h after 6-OHDA injection. Eight days after 6-OHDA application, behavioral studies (adhesive tape removal test, open-field test, cylinder test, and apomorphine-induced asymmetric rotational behavior) were performed once more to compare the effects of CAPE on behavior tests. Striatal histological verifications, immunohistochemistry, and stereological quantitation were performed. Our results for the first time showed that, besides improving the motor performance, CAPE treatment also prevents 6-OHDA-induced loss of TH-positive neurons. From our results, CAPE may be a promising clinical agent in the treatment of PD.

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