Commentary: Evaluation of Models of Parkinson's Disease

Leal, Pollyana Caldeira; Lins, Lucas Correia; Gois, Auderlan M.; Marchioro, Murilo; Santos, José R.

doi:10.3389/fnins.2016.00283

Cited by 16 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, the functional interplay between D 2 R and M 1 R was demonstrated by the co-administration of a D 2 R agonist and an M 1 R antagonist to reserpinized mice, which is an animal model mimicking parkinsonian motor and non-motor impairments (Leao et al, 2015;Leal et al, 2016). The major disadvantage of this model is the lack of dopaminergic neurons degeneration and protein aggregation.…”

Section: Discussionmentioning

confidence: 76%

“…Therefore, we hypothesized that this receptor-receptor interaction might constitute a molecular target for multimodal pharmacological interventions finely controlling striatal motor activity. Accordingly, we tested the effects of a combined drug treatment regimen (D 2 R agonist + M 1 R antagonist) in a wellknown model of movement disorder, i.e., the reserpinized mouse (Leao et al, 2015;Leal et al, 2016). The drugs used were the D 2 Rselective agonist sumanirole and the M 1 R-selective antagonist VU0255035.…”

Section: Multimodal D 2 R Agonist and M 1 R Antagonist Treatment Of Rmentioning

confidence: 99%

See 1 more Smart Citation

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor–Receptor Interaction in a Model of Movement Disorders

et al. 2020

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor control deficits, which is associated with the loss of striatal dopaminergic neurons from the substantia nigra. In parallel to dopaminergic denervation, there is an increase of acetylcholine within the striatum, resulting in a striatal dopaminergiccholinergic neurotransmission imbalance. Currently, available PD pharmacotherapy (e.g., prodopaminergic drugs) does not reinstate the altered dopaminergic-cholinergic balance. In addition, it can eventually elicit cholinergic-related adverse effects. Here, we investigated the interplay between dopaminergic and cholinergic systems by assessing the physical and functional interaction of dopamine D 2 and muscarinic acetylcholine M 1 receptors (D 2 R and M 1 R, respectively), both expressed at striatopallidal medium spiny neurons. First, we provided evidence for the existence of D 2 R-M 1 R complexes via biochemical (i.e., co-immunoprecipitation) and biophysical (i.e., BRET 1 and NanoBiT R ) assays, performed in transiently transfected HEK293T cells. Subsequently, a D 2 R-M 1 R co-distribution in the mouse striatum was observed through doubleimmunofluorescence staining and AlphaLISA R immunoassay. Finally, we evaluated the functional interplay between both receptors via behavioral studies, by implementing the classical acute reserpine pharmacological animal model of experimental parkinsonism. Reserpinized mice were administered with a D 2 R-selective agonist (sumanirole) and/or an M 1 R-selective antagonist (VU0255035), and alterations in PD-related behavioral tasks (i.e., locomotor activity) were evaluated. Importantly, VU0255035 (10 mg/kg) potentiated the antiparkinsonian-like effects (i.e., increased locomotor activity and decreased catalepsy) of an ineffective sumanirole dose (3 mg/kg). Altogether, our data suggest the existence of putative striatal D 2 R/M 1 R heteromers, which might be a relevant target to manage PD motor impairments with fewer adverse effects.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Multimodal D 2 R Agonist and M 1 R Antagonist Treatment Of Rmentioning

confidence: 99%

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor–Receptor Interaction in a Model of Movement Disorders

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Such skeletal muscle abnormalities are characteristic for Parkinson disease and include bradykinesia, akinesia, and at-rest tremors [3]. Parkinson disease can be induced in rodents by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which primes dopaminergic neurons to degenerate, causing significant dopamine depletion characteristic for PD [4–9].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 Beta and Tumor Necrosis Factor Alpha Upregulation and Nuclear Factor Kappa B Activation in Skeletal Muscle from a Mouse Model of Chronic/Progressive Parkinson Disease

Erekat

Al-Jarrah

2018

Med Sci Monit

View full text Add to dashboard Cite

Background Skeletal muscle atrophy has been reported in patients with Parkinson disease (PD). The purpose of this study was to examine the potential implication of interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF kappa B) in skeletal muscle atrophy following PD induction. Material/Methods Chronic Parkinsonism was induced in 10 albino mice by MPTP/probenecid treatment, while 10 other albino mice remained without treatment and were subsequently used as controls. Gastrocnemius muscles were examined for the expression of IL-1β and TNF-α, as well as the nuclear localization of NF kappa B, indicative of its activation, using immunohistochemistry in the 2 different groups. Results IL-1β and TNF-α expression and NF kappa B nuclear localization were significantly higher in the PD skeletal muscle compared with those in the controls (P value <0.01). Conclusions The present data are indicative of an association of PD with IL-1β and TNF-α upregulation and NF kappa B activation in gastrocnemius muscles, potentially promoting the atrophy frequently observed in PD.

show abstract

“…They include rotenone, MPTP, paraquat, 6-hydroxydopamine (6-0HDA), genetic, and immune-related models. [ 135 194 233 ] Genetic models will not be considered here as this paper is more concerned with sporadic Parkinson disease.…”

Section: Part IImentioning

confidence: 99%

“…Many of these models do not reflect human cases of the disorder. [ 135 ] This is especially so for the toxic models. For example, neither the MPTP nor 6-hydroxydopamine models induced Lewy bodies.…”

Section: Part IImentioning

confidence: 99%

Parkinson's disease: Microglial/macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration

Blaylock¹

2017

Surg Neurol Int

View full text Add to dashboard Cite

Parkinson's disease is one of the several neurodegenerative disorders that affects aging individuals, with approximately 1% of those over the age of 60 years developing the disorder in their lifetime. The disease has the characteristics of a progressive disorder in most people, with a common pattern of pathological change occurring in the nervous system that extends beyond the classical striatal degeneration of dopaminergic neurons. Earlier studies concluded that the disease was a disorder of alpha-synuclein, with the formation of aggregates of abnormal alpha-synuclein being characteristic. More recent studies have concluded that inflammation plays a central role in the disorder and that the characteristic findings can be accounted for by either mutation or oxidative damage to alpha-synuclein, with resulting immune reactions from surrounding microglia, astrocytes, and macrophages. What has been all but ignored in most of these studies is the role played by excitotoxicity and that the two processes are intimately linked, with inflammation triggered cell signaling enhancing the excitotoxic cascade. Further, there is growing evidence that it is the excitotoxic reactions that actually cause the neurodegeneration. I have coined the name immunoexcitotoxicity to describe this link between inflammation and excitotoxicity. It appears that the two processes are rarely, if ever, separated in neurodegenerative diseases.

show abstract

Commentary: Evaluation of Models of Parkinson's Disease

Cited by 16 publications

References 28 publications

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor–Receptor Interaction in a Model of Movement Disorders

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor–Receptor Interaction in a Model of Movement Disorders

Interleukin-1 Beta and Tumor Necrosis Factor Alpha Upregulation and Nuclear Factor Kappa B Activation in Skeletal Muscle from a Mouse Model of Chronic/Progressive Parkinson Disease

Parkinson's disease: Microglial/macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration

Contact Info

Product

Resources

About