scholarly journals 6-hydroxydopamine-induced Parkinson's disease-like degeneration generates acute microgliosis and astrogliosis in the nigrostriatal system but no bioluminescence imaging-detectable alteration in adult neurogenesis

2016 ◽  
Vol 43 (10) ◽  
pp. 1352-1365 ◽  
Author(s):  
Inga B. Fricke ◽  
Thomas Viel ◽  
Maik M. Worlitzer ◽  
Franziska M. Collmann ◽  
Alexis Vrachimis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adult Neurogenesis ◽  
Bioluminescence Imaging ◽  
Nigrostriatal System ◽  
6 Hydroxydopamine

scholarly journals Neuroprotection and Functional Recovery Associated with Decreased Microglial Activation Following Selective Activation of mGluR2/3 Receptors in a Rodent Model of Parkinson's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Hugh Chan ◽  
Helen Paur ◽  
Anthony C. Vernon ◽  
Virginia Zabarsky ◽  
Krishna P. Datla ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Recovery ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Excitotoxicity ◽  
Nigrostriatal System ◽  
Antiinflammatory Action ◽  
Metabotropic Glutamate ◽  
Beneficial Effects ◽  
6 Hydroxydopamine

Clinical trials have demonstrated positive proof of efficacy of dual metabotropic glutamate receptor 2/3 (mGluR2/3) agonists in both anxiety and schizophrenia. Importantly, evidence suggests that these drugs may also be neuroprotective against glutamate excitotoxicity, implicated in the pathogenesis of Parkinson's disease (PD). However, whether this neuroprotection also translates into functional recovery is unclear. In the current study, we examined the neuroprotective efficacy of the dual mGluR2/3 agonist, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), and whether this is accompanied by behavioral recovery in a rodent 6-hydroxydopamine (6-OHDA) model of PD. We now report that delayed post lesion treatment with 2R,4R-APDC (10 nmol), results in robust neuroprotection of the nigrostriatal system, which translated into functional recovery as measured by improved forelimb use asymmetry and reduced (+)-amphetamine-induced rotation compared to vehicle treated animals. Interestingly, these beneficial effects were associated with a decrease in microglial markers in the SNc, which may suggest an antiinflammatory action of this drug.

The Dynamics of Nigrostriatal System Damage and Neurobehavioral Changes in the Rotenone Rat Model of Parkinson's Disease

2021 ◽  
Author(s):  
Dmitry Troshev ◽  
Daniil Berezhnoy ◽  
Olga Kulikova ◽  
Denis Abaimov ◽  
Olga Muzychuk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Nigrostriatal System

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 A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 598
Author(s):  
Débora Masini ◽  
Carina Plewnia ◽  
Maëlle Bertho ◽  
Nicolas Scalbert ◽  
Vittorio Caggiano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Survival Rates ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Operative Care ◽  
6 Hydroxydopamine ◽  
Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

scholarly journals The Protective Role of Brain CYP2J in Parkinson’s Disease Models

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yueran Li ◽  
Jinhua Wu ◽  
Xuming Yu ◽  
Shufang Na ◽  
Ke Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Protective Role ◽  
Neural Cells ◽  
Endogenous Substrates ◽  
6 Hydroxydopamine ◽  
Myd88 Signaling ◽  
Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

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