6-Hydroxydopamine: a far from simple neurotoxin

Varešlija, Damir; Tipton, Keith F.; Davey, Gavin P.; McDonald, Andrew G.

doi:10.1007/s00702-019-02133-6

Cited by 44 publications

(19 citation statements)

References 178 publications

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“…The inhibition of brain mitochondrial complexes (I and IV) and oxidation to form semiquinone radicals (which participate in reactive oxygen species production) are the main biochemical properties of 6-OHDA. Then the toxicity results in the loss of respiratory activity from oxidative stress by free radicals [ 82 , 83 ]. Rodriguez-Pallares et al (2007) data showed that the autooxidation-derived oxidative stress and the inhibition of the mitochondrial respiratory chain, initially microglial stimulation and NADPH oxidase-derived reactive oxygen species functions synthetically with 6-OHDA and establish an appropriate and early constituent of 6-OHDA-convinced cell death ( Figure 4 ) [ 84 ].…”

Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

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Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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“…It is known that the dopamine and serotonin tissue levels in the striatum and other brain areas such as the cerebral cortex and the hippocampus, decrease as a consequence of 6-OHDA intrastriatal injection [ 23 , 24 , 25 ]. 6-OHDA selectively destroys dopaminergic neurons due to its high affinity to the dopamine transporter [ 26 , 27 ]. 6-OHDA can also destroy adjacent cells as a result of the formation of ROS [ 16 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…6-OHDA selectively destroys dopaminergic neurons due to its high affinity to the dopamine transporter [ 26 , 27 ]. 6-OHDA can also destroy adjacent cells as a result of the formation of ROS [ 16 , 27 ]. This situation explains the simultaneous changes in dopamine and serotonin in different brain areas induced by 6-OHDA.…”

Section: Discussionmentioning

confidence: 99%

Transcranial Focal Electrical Stimulation Modifies Biogenic Amines’ Alterations Induced by 6-Hydroxydopamine in Rat Brain

Santana-Gomez

Pérez-Pérez²,

Fonseca-Barriendos³

et al. 2021

Pharmaceuticals

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Transcranial focal stimulation (TFS) is a non-invasive neuromodulation strategy with neuroprotective effects. On the other hand, 6-hidroxidopamine (6-OHDA) induces neurodegeneration of the nigrostriatal system producing modifications in the dopaminergic, serotoninergic, and histaminergic systems. The present study was conducted to test whether repetitive application of TFS avoids the biogenic amines’ changes induced by the intrastriatal injection of 6-OHDA. Experiments were designed to determine the tissue content of dopamine, serotonin, and histamine in the brain of animals injected with 6-OHDA and then receiving daily TFS for 21 days. Tissue content of biogenic amines was evaluated in the cerebral cortex, hippocampus, amygdala, and striatum, ipsi- and contralateral to the side of 6-OHDA injection. Results obtained were compared to animals with 6-OHDA, TFS alone, and a Sham group. The present study revealed that TFS did not avoid the changes in the tissue content of dopamine in striatum. However, TFS was able to avoid several of the changes induced by 6-OHDA in the tissue content of dopamine, serotonin, and histamine in the different brain areas evaluated. Interestingly, TFS alone did not induce significant changes in the different brain areas evaluated. The present study showed that repetitive TFS avoids the biogenic amines’ changes induced by 6-OHDA. TFS can represent a new therapeutic strategy to avoid the neurotoxicity induced by 6-OHDA.

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“…Reduced blood flow secondary to arteriosclerosis causes ischemia, infiltration of inflammatory cells, and subsequent necrosis. HIV-1 infection also promotes extramedullary hematopoiesis in the bone marrow, perhaps compensating for inflammation-induced impairment of this function in the splenic red pulp [ 109 , 126 , 127 , 128 , 129 ].…”

Section: Hiv-1 Establishes Cellular Reservoirs and Induces Splenocyte...mentioning

confidence: 99%

Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

Bellinger

Lorton

2022

Cells

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The immune and sympathetic nervous systems are major targets of human, murine and simian immunodeficiency viruses (HIV-1, MAIDS, and SIV, respectively). The spleen is a major reservoir for these retroviruses, providing a sanctuary for persistent infection of myeloid cells in the white and red pulps. This is despite the fact that circulating HIV-1 levels remain undetectable in infected patients receiving combined antiretroviral therapy. These viruses sequester in immune organs, preventing effective cures. The spleen remains understudied in its role in HIV-1 pathogenesis, despite it hosting a quarter of the body’s lymphocytes and diverse macrophage populations targeted by HIV-1. HIV-1 infection reduces the white pulp, and induces perivascular hyalinization, vascular dysfunction, tissue infarction, and chronic inflammation characterized by activated epithelial-like macrophages. LP-BM5, the retrovirus that induces MAIDS, is a well-established model of AIDS. Immune pathology in MAIDs is similar to SIV and HIV-1 infection. As in SIV and HIV, MAIDS markedly changes splenic architecture, and causes sympathetic dysfunction, contributing to inflammation and immune dysfunction. In MAIDs, SIV, and HIV, the viruses commandeer splenic macrophages for their replication, and shift macrophages to an M2 phenotype. Additionally, in plasmacytoid dendritic cells, HIV-1 blocks sympathetic augmentation of interferon-β (IFN-β) transcription, which promotes viral replication. Here, we review viral–sympathetic interactions in innate immunity and pathophysiology in the spleen in HIV-1 and relevant models. The situation remains that research in this area is still sparse and original hypotheses proposed largely remain unanswered.

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6-Hydroxydopamine: a far from simple neurotoxin

Cited by 44 publications

References 178 publications

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Transcranial Focal Electrical Stimulation Modifies Biogenic Amines’ Alterations Induced by 6-Hydroxydopamine in Rat Brain

Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

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