Behavioral, cellular and molecular responses to cold and mechanical stimuli in rats with bilateral dopamine depletion in the mesencephalic dopaminergic neurons

Neuroscience ◽  
2021 ◽  
Author(s):  
Mennatallah Elshennawy ◽  
Omar Ouachikh ◽  
Youssef Aissouni ◽  
Shahira Youssef ◽  
Shahira S. Zaki ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Mechanical Stimuli ◽  
Dopamine Depletion ◽  
Molecular Responses

scholarly journals Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
A. Machado ◽  
A. J. Herrera ◽  
J. L. Venero ◽  
M. Santiago ◽  
R. M. de Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Dopaminergic Neurons ◽  
Inflammatory Process ◽  
Dopaminergic System ◽  
Neuronal System ◽  
Dopamine Depletion ◽  
Anti Inflammatory ◽  
Dopaminergic Degeneration

We have developed an animal model of degeneration of the nigrostriatal dopaminergic neurons, the neuronal system involved in Parkinson's disease (PD). The implication of neuroinflammation on this disease was originally established in 1988, when the presence of activated microglia in the substantia nigra (SN) of parkinsonians was reported by McGeer et al. Neuroinflammation could be involved in the progression of the disease or even has more direct implications. We injected 2 μg of the potent proinflammatory compound lipopolysaccharide (LPS) in different areas of the CNS, finding that SN displayed the highest inflammatory response and that dopaminergic (body) neurons showed a special and specific sensitivity to this process with the induction of selective dopaminergic degeneration. Neurodegeneration is induced by inflammation since it is prevented by anti-inflammatory compounds. The special sensitivity of dopaminergic neurons seems to be related to the endogenous dopaminergic content, since it is overcome by dopamine depletion. Compounds that activate microglia or induce inflammation have similar effects to LPS. This model suggest that inflammation is an important component of the degeneration of the nigrostriatal dopaminergic system, probably also in PD. Anti-inflammatory treatments could be useful to prevent or slow down the rate of dopaminergic degeneration in this disease.

scholarly journals Gastrodin Protects Apoptotic Dopaminergic Neurons in a Toxin-Induced Parkinson’s Disease Model

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Hemant Kumar ◽  
In-Su Kim ◽  
Sandeep Vasant More ◽  
Byung-Wook Kim ◽  
Young-Yil Bahk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Disease Model ◽  
Motor Impairment ◽  
Protective Effects ◽  
Dopamine Depletion ◽  
Active Constituent ◽  
Neuroprotective Effects ◽  
Phenolic Glucoside

Gastrodia elata(GE) Blume is one of the most important traditional plants in Oriental countries and has been used for centuries to improve various conditions. The phenolic glucoside gastrodin is an active constituent of GE. The aim of this study was to investigate the neuroprotective role of gastrodin in 1-methyl-4-phenylpyridinium (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) induced human dopaminergic SH-SY5Y cells and mouse model of Parkinson’s disease (PD), respectively. Gastrodin significantly and dose dependently protected dopaminergic neurons against neurotoxicity through regulating free radicals, Bax/Bcl-2 mRNA, caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) in SH-SY5Y cells stressed with MPP+. Gastrodin also showed neuroprotective effects in the subchronic MPTP mouse PD model by ameliorating bradykinesia and motor impairment in the pole and rotarod tests, respectively. Consistent with this finding, gastrodin prevented dopamine depletion and reduced reactive astrogliosis caused by MPTP as assessed by immunohistochemistry and immunoblotting in the substantiae nigrae and striatata of mice. Moreover, gastrodin was also effective in preventing neuronal apoptosis by attenuating antioxidant and antiapoptotic activities in these brain areas. These results strongly suggest that gastrodin has protective effects in experimental PD models and that it may be developed as a clinical candidate to ameliorate PD symptoms.

scholarly journals Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2441
Author(s):  
Victoria Sofie Witzig ◽  
Daniel Komnig ◽  
Björn H. Falkenburger
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Morphological Changes ◽  
Medium Spiny Neuron ◽  
Motor Complications ◽  
Spine Density ◽  
Branch Points ◽  
Dopamine Depletion ◽  
Axon Terminals

The classical motor symptoms of Parkinson’s disease (PD) are caused by degeneration of dopaminergic neurons in the substantia nigra, which is followed by secondary dendritic pruning and spine loss at striatal medium spiny neurons (MSN). We hypothesize that these morphological changes at MSN underlie at least in part long-term motor complications in PD patients. In order to define the potential benefits and limitations of dopamine substitution, we tested in a mouse model whether dendritic pruning and spine loss can be reversible when dopaminergic axon terminals regenerate. In order to induce degeneration of nigrostriatal dopaminergic neurons we used the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6J mice; 30 mg/kg MPTP was applied i.p. on five consecutive days. In order to assess the consequences of dopamine depletion, mice were analyzed 21 days after the last injection. In order to test reversibility of MSN changes we exploited the property of this model that striatal axon terminals regenerate by sprouting within 90 days and analyzed a second cohort 90 days after MPTP. Degeneration of dopaminergic neurons was confirmed by counting TH-positive neurons in the substantia nigra and by analyzing striatal catecholamines. Striatal catecholamine recovered 90 days after MPTP. MSN morphology was visualized by Golgi staining and quantified as total dendritic length, number of dendritic branch points, and density of dendritic spines. All morphological parameters of striatal MSN were reduced 21 days after MPTP. Statistical analysis indicated that dendritic pruning and the reduction of spine density represent two distinct responses to dopamine depletion. Ninety days after MPTP, all morphological changes recovered. Our findings demonstrate that morphological changes in striatal MSN resulting from dopamine depletion are reversible. They suggest that under optimal conditions, symptomatic dopaminergic therapy might be able to prevent maladaptive plasticity and long-term motor complications in PD patients.

scholarly journals p21 inhibitor UC2288 ameliorates MPTP induced Parkinson’s disease progression through inhibition of oxidative stress and neuroinflammation

2020 ◽  
Author(s):  
Jun Hyung Im ◽  
In Jun Yeo ◽  
Seong Hee Jeon ◽  
Dong Hun Lee ◽  
Hyeon Joo Ham ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Disease ◽  
Dopaminergic Neurons ◽  
Kinase Inhibitor ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cultured Neurons ◽  
Dopamine Depletion ◽  
Erk Kinase

Abstract BackgroundParkinson's disease (PD) is a neurodegenerative disease characterized by the early prominent death of dopaminergic neurons and a decrease of dopamine levels. Dopamine depletion leads to several motor dysfunctions, including resting tremor, muscular rigidity, bradykinesia and postural instability. Our previous study determined that knockout of parkin, a gene of PD degrade p21, suppresses neurogenesis which is critical for a neurodegenerative disease. MethodsThus, we investigated the effect of UC2288, an inhibitor of p21, for its therapeutic effect on PD. We found that UC2288 attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment in Rota-rod and Pole test as well as dopamine depletion.ResultsMoreover, UC2288 recovered the number of TH positive cells, but decreased the number of GFAP and Iba-1 positive cells accompanied the decrease of BAX and cleaved caspase3 as well as iNOS and COX-2 expression. In cultured neurons, UC2288 recovered MPP+-induced neuronal cell death in a concentration dependent manner. We also found that UC2288 decreased the p21 reactive cell number, oxidative neuronal damages, cytokines product in vivo and cultured neurons. In a mechanism study, we found that UC2288 significantly decreased the activation of ERK and p38 kinase pathway in the mitogen-activated protein kinase (MAPK) pathway. In addition, 1-10 μM concentration of ERK kinase inhibitor U0126 recovered MPP+-induced neuronal cell death. However, ERK kinase inhibitor U0126 further decreased cell viability with the increase of H2O2.ConclusionThese results indicated that the administration of UC2288 exerted neuroprotective effects on the death of dopaminergic neurons through the suppression of oxidative stress and neuroinflammation via ERK pathway inhibition.

scholarly journals Dopamine role in learning and action inference

2019 ◽  
Author(s):  
Rafal Bogacz
Keyword(s):  
Basal Ganglia ◽  
Dopaminergic Neurons ◽  
Habit Formation ◽  
Action Planning ◽  
Mammalian Brain ◽  
Prediction Errors ◽  
Dopamine Depletion ◽  
Motor Plan ◽  
Directed System ◽  
Different Parts

AbstractThis paper describes a framework for modelling dopamine function in the mammalian brain. In this framework, dopaminergic neurons projecting to different parts of the striatum encode errors in predictions made by the corresponding systems within the basal ganglia. These prediction errors are equal to differences between rewards and expectations in the goal-directed system, and to differences between the chosen and habitual actions in the habit system. The prediction errors enable learning about rewards resulting from actions and habit formation. During action planning, the expectation of reward in the goal-directed system arises from formulating a plan to obtain that reward. Thus dopaminergic neurons in this system provide feedback on whether the current motor plan is sufficient to obtain the available reward, and they facilitate action planning until a suitable plan is found. Presented models account for dopaminergic responses during movements, effects of dopamine depletion on behaviour, and make several experimental predictions.

scholarly journals Batryticatus Bombyx Protects Dopaminergic Neurons against MPTP-Induced Neurotoxicity by Inhibiting Oxidative Damage

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Joong-Sun Kim ◽  
Byeong Cheol Moon ◽  
Seung Mok Ryu ◽  
Jun Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Dopaminergic Neurons ◽  
Redox Homeostasis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Substantia Nigra Pars Compacta ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Dopamine Depletion ◽  
Behavioral Impairments

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Altered redox homeostasis in neurons interferes with several biological processes, ultimately leading to neuronal death. Oxidative damage has been identified as one of the principal mechanisms underlying the progression of PD. Several studies highlight the key role of superoxide radicals in inducing neuronal toxicity. Batryticatus Bombyx (BB), the dried larva of Bombyx mori L. infected by Beauveria bassiana (Bals.) Vuill., has been used in traditional medicine for its various pharmacological effects. In the present study, BB showed a beneficial effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by directly targeting dopaminergic neurons. Treatment with BB improved behavioral impairments, protected dopaminergic neurons, and maintained dopamine levels in PD mouse models. Here, we investigated the protective effects of BB on MPTP-induced PD in mice and explored the underlying mechanisms of action, focusing on oxidative signaling. In MPTP-induced PD, BB promoted recovery from impaired movement, prevented dopamine depletion, and protected against dopaminergic neuronal degradation in the substantia nigra pars compacta (SNpc) or the striatum (ST). Moreover, BB upregulated mediators of antioxidative response such as superoxidase dismutase (SOD), catalase (CAT), glutathione (GSH), Heme oxygenase 1 (HO-1), and NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase (NQO1). Thus, treatment with BB reduced the oxidative stress, improved behavioral impairments, and protected against dopamine depletion in MPTP-induced toxicity.

scholarly journals Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Hye-Sun Lim ◽  
Joong-Sun Kim ◽  
Byeong Cheol Moon ◽  
Goya Choi ◽  
Seung Mok Ryu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Microglial Activation ◽  
Neuronal Loss ◽  
B Cell Lymphoma ◽  
Nuclear Hormone Receptor ◽  
Substantia Nigra Pars Compacta ◽  
Protective Effects ◽  
Dopamine Depletion

Parkinson’s disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.

scholarly journals Preparation and Neuroprotective Activity of Glucuronomannan Oligosaccharides in an MPTP-Induced Parkinson’s Model

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 438
Author(s):  
Yingjuan Liu ◽  
Weihua Jin ◽  
Zhenzhen Deng ◽  
Jing Wang ◽  
Quanbin Zhang
Keyword(s):  
Dopaminergic Neurons ◽  
Complex Structure ◽  
Saccharina Japonica ◽  
Neuroprotective Activity ◽  
Dopamine Depletion ◽  
Neuron Degeneration ◽  
Neuroprotective Effects ◽  
Behavioral Deficits ◽  
Antioxidative Stress ◽  
Global Population

Parkinson’s disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra and dopamine depletion in the striatum, affects up to 1% of the global population over 50 years of age. Our previous study found that a heteropolysaccharide from Saccharina japonica exhibits neuroprotective effects through antioxidative stress. In view of its high molecular weight and complex structure, we degraded the polysaccharide and subsequently obtained four oligosaccharides. In this study, we aimed to further detect the neuroprotective mechanism of the oligosaccharides. We applied MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to induce PD, and glucuronomannan oligosaccharides (GMn) was subsequently administered. Results showed that GMn ameliorated behavioral deficits in Parkinsonism mice. Furthermore, we observed that glucuronomannan oligosaccharides contributed to down-regulating the apoptotic signaling pathway through enhancing the expression of tyrosine hydroxylase (TH) in dopaminergic neurons. These results suggest that glucuronomannan oligosaccharides protect dopaminergic neurons from apoptosis in PD mice.

scholarly journals Dopamine role in learning and action inference

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Rafal Bogacz
Keyword(s):  
Basal Ganglia ◽  
Dopaminergic Neurons ◽  
Habit Formation ◽  
Action Planning ◽  
Mammalian Brain ◽  
Prediction Errors ◽  
Dopamine Depletion ◽  
Directed System ◽  
The Difference ◽  
Different Parts

This paper describes a framework for modelling dopamine function in the mammalian brain. It proposes that both learning and action planning involve processes minimizing prediction errors encoded by dopaminergic neurons. In this framework, dopaminergic neurons projecting to different parts of the striatum encode errors in predictions made by the corresponding systems within the basal ganglia. The dopaminergic neurons encode differences between rewards and expectations in the goal-directed system, and differences between the chosen and habitual actions in the habit system. These prediction errors trigger learning about rewards and habit formation, respectively. Additionally, dopaminergic neurons in the goal-directed system play a key role in action planning: They compute the difference between a desired reward and the reward expected from the current motor plan, and they facilitate action planning until this difference diminishes. Presented models account for dopaminergic responses during movements, effects of dopamine depletion on behaviour, and make several experimental predictions.

scholarly journals Dopaminergic pathway and athletic mind

2021 ◽  
pp. 29-39
Keyword(s):  
Decision Making ◽  
Key Words ◽  
Motor Skills ◽  
Athletic Performance ◽  
Dopaminergic Neurons ◽  
Essential Role ◽  
Search Strategy ◽  
Mental Fatigue ◽  
Dopamine Depletion ◽  
Dopaminergic Pathway

Purpose: we reviewed that the mental fatigue is influenced by dopamine depletion, and we assume that increasing DA level can increase athletic stamina and promote athletic performance after prolong exercise. Methods: The search strategy was according to key words contain, Mental fatigue , Decision making , Dopamine, Stroboscope training through the Google scholar, PubMed, and Elsevier. Among the literatures, 100 papers include review and original articles were studied. Finally, we decided to select 49 papers based on similarity and recent studies so more than 50 percent of papers were excluded, because of they were out of date or irrelevant to key words. Results: Based on many studies, it was found dopamine has an essential role on athletic performance and his stamina. Conclusion: The stroboscope vision training in sports could enhance the dopaminergic neurons and associated visuo-motor skills

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