Dopamine Cell Degeneration Induced by Intraventricular Administration of 6-Hydroxydopamine in the Rat: Similarities with Cell Loss in Parkinson's Disease

2001 ◽  
Vol 169 (1) ◽  
pp. 163-181 ◽  
Author(s):  
Manuel Rodrı́guez ◽  
Pedro Barroso-Chinea ◽  
Patricio Abdala ◽  
José Obeso ◽  
Tomás González-Hernández
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Loss ◽  
Intraventricular Administration ◽  
Cell Degeneration ◽  
6 Hydroxydopamine ◽  
Dopamine Cell

Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson's disease

2018 ◽  
Vol 304 ◽  
pp. 143-153 ◽  
Author(s):  
Claude Rouillard ◽  
Joanie Baillargeon ◽  
Brigitte Paquet ◽  
Michel St-Hilaire ◽  
Jérôme Maheux ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nuclear Receptor ◽  
Cell Loss ◽  
Dopamine Cell

scholarly journals Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease: removing axonal debris

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Ingrid Morales ◽  
Ricardo Puertas-Avendaño ◽  
Alberto Sanchez ◽  
Adrian Perez-Barreto ◽  
Clara Rodriguez-Sabate ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Medial Forebrain Bundle ◽  
Physiological Role ◽  
Cell Degeneration ◽  
Retrograde Degeneration ◽  
Microglial Phagocytosis ◽  
Transporter Protein ◽  
Cellular Debris ◽  
6 Hydroxydopamine

Abstract Objective The dopaminergic nigrostriatal neurons (DA cells) in healthy people present a slow degeneration with aging, which produces cellular debris throughout life. About 2%–5% of people present rapid cell degeneration of more than 50% of DA cells, which produces Parkinson’s disease (PD). Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells, particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic axons. As synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation, this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells, paying particular attention to the relative roles of astrocytes and microglia. Methods Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine, inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage, microgliosis or neuroinflammation. The possible retrograde degeneration of dopaminergic axons, and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy images. Results The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain bundle. These spheroids retained mitochondria and most (e.g., tyrosine hydroxylase, the dopamine transporter protein, and amyloid precursor protein) but not all (e.g., α-synuclein) proteins of the degenerating dopaminergic axons. Spheroids showed initial (autophagosomes) but not late (lysosomes) components of autophagy (incomplete autophagy). These spheroids were penetrated by astrocytic processes of the medial forebrain bundle, which provided the lysosomes needed to continue the degradation of dopaminergic debris. Finally, dopaminergic proteins were observed in the cell somata of astrocytes. No microgliosis or microglial phagocytosis of debris was observed in the medial forebrain bundle during the retrograde degeneration of dopaminergic axons. Conclusions The present data suggest a physiological role of astrocytic phagocytosis of axonal debris for the medial forebrain bundle astrocytes, which may prevent the activation of microglia and the spread of retrograde axonal degeneration in PD.

scholarly journals Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson’s Disease Mouse Model

2021 ◽  
Vol 22 (21) ◽  
pp. 11328
Author(s):  
Helena Berlamont ◽  
Arnout Bruggeman ◽  
Eva Bauwens ◽  
Charysse Vandendriessche ◽  
Elien Clarebout ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Neuroprotective Effect ◽  
Cell Loss ◽  
Antioxidant Genes ◽  
Exact Etiology ◽  
Gastric Biopsies ◽  
6 Hydroxydopamine

The exact etiology of Parkinson’s disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis (H. suis) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis-infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis-infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.

Aberrant reward processing in Parkinson's disease is associated with dopamine cell loss

NeuroImage ◽  
2012 ◽  
Vol 59 (4) ◽  
pp. 3339-3346 ◽  
Author(s):  
Esther Aarts ◽  
Rick C. Helmich ◽  
Marcel J.R. Janssen ◽  
Wim J.G. Oyen ◽  
Bastiaan R. Bloem ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Loss ◽  
Reward Processing ◽  
Dopamine Cell

scholarly journals Rhododendrin-Induced RNF146 Expression via Estrogen Receptor β Activation is Cytoprotective Against 6-OHDA-Induced Oxidative Stress

2019 ◽  
Vol 20 (7) ◽  
pp. 1772 ◽  
Author(s):  
Hyojung Kim ◽  
Jisoo Park ◽  
HyunHee Leem ◽  
MyoungLae Cho ◽  
Jin-Ha Yoon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Estrogen Receptor ◽  
Nuclear Translocation ◽  
Ring Finger ◽  
Cell Loss ◽  
Receptor Activation ◽  
Estrogen Receptor Β ◽  
Dopaminergic Cell ◽  
6 Hydroxydopamine

Ring finger protein 146 (RNF146) is an E3 ubiquitin ligase whose activity prevents poly (ADP-ribose) polymerase 1 (PARP1)-dependent neurodegeneration in Parkinson’s disease (PD). Previously, we reported that rhododendrin is a chemical inducer that increases RNF146 expression. However, the molecular mechanism of rhododendrin-induced RNF146 expression is largely unknown and its translational application for the treatment of Parkinson’s disease remains unexplored. Here we found that rhododendrin increased RNF146 expression via estrogen receptor β (ERβ) activation. Rhododendrin stimulated ERβ nuclear translocation and binding to the RNF146 promoter, thereby enhancing its transcription. Rhododendrin is cytoprotective against 6-hydroxydopamine (6-OHDA)-induced cell death, which is largely dependent on ERβ activity and RNF146 expression. Finally, we demonstrated that rhododendrin treatment resulted in RNF146 expression in dopaminergic neurons in mice. Moreover, dopaminergic neuron viability was markedly enhanced by pretreatment with rhododendrin in 6-OHDA-induced mouse models for PD. Our findings indicate that estrogen receptor activation plays a neuroprotective role and that rhododendrin could be a potential therapeutic agent in preventing PARP1-dependent dopaminergic cell loss in PD.

scholarly journals Coenzyme Q Induces Nigral Mitochondrial Uncoupling and Prevents Dopamine Cell Loss in a Primate Model of Parkinson’s Disease

Endocrinology ◽  
2003 ◽  
Vol 144 (7) ◽  
pp. 2757-2760 ◽  
Author(s):  
Tamas L. Horvath ◽  
Sabrina Diano ◽  
Csaba Leranth ◽  
Luis Miguel Garcia-Segura ◽  
Michael A. Cowley ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Coenzyme Q ◽  
Cell Loss ◽  
Dopamine Neurons ◽  
Short Term ◽  
Mitochondrial Uncoupling ◽  
Primate Model ◽  
Mitochondrial Uncoupling Proteins ◽  
Dopamine Cell

Abstract Parkinson’s disease is characterized by dopamine cell loss of the substantia nigra. Parkinson’s disease and the neurotoxin 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine may destroy dopamine neurons through oxidative stress. Coenzyme Q is a cofactor of mitochondrial uncoupling proteins that enhances state-4 respiration and eliminate superoxides. Here we report that short-term oral administration of coenzyme Q induces nigral mitochondrial uncoupling and prevents dopamine cell loss after 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine administration in monkeys.

scholarly journals Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease

2016 ◽  
Vol 89 ◽  
pp. 55-64 ◽  
Author(s):  
Ludovico Arcuri ◽  
Riccardo Viaro ◽  
Simone Bido ◽  
Francesco Longo ◽  
Mariangela Calcagno ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Loss ◽  
Orphanin Fq ◽  
Dopamine Cell
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