Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo 1H-MRS study of an animal model for Parkinson's disease

Objective: To use 1.5T 1H-MRS as a research tool in vivo and demonstrate the feasibility of obtaining long-echo 1H MR spectra in small volumes like substantia nigra (SN) and medulla oblongata (MO) in healthy volunteers and patients with Parkinson's disease (PD) and observe the clinical correlations. Subjects and Methods: Twenty patients of the idiopathic Parkinson’s disease (IPD) were recruited from the Out Patient Department of Neurology. Additionally, 14 age-matched healthy subjects were taken as controls group. After baseline evaluation, the patients satisfying inclusion and exclusion criteria underwent 1H-MRS study. All MR examinations were performed on a 1.5 T system (Philips Gyroscan Intera, Netherlands) using a standard quadrature head coil. Results: We succeeded to achieve 74.19% and 77.42% of spectra from MO and SN of both PD and control groups. MO showed slightly weak negative result to total UPDRS and UPDRS- II, but no significant correlation was found between metabolites and clinical indexes in MO. The result also showed no significant correlations between H&Y scale and metabolites in MO and SN of PD patients. But there was a significant correlation between H&Y, NAA/Cr and Cho/Cr in SN. Conclusions: MRS ratios from MO and SN does not play any significant role to differentiate PD from the normal subjects, but metabolites ratios from SN of PD patient can help to understand the progression and severity of the disease. Therefore, it is not practical to employ MRS as a diagnostic tool for PD. DOI: http://dx.doi.org/10.3126/ajms.v4i3.8066 Asian Journal of Medical Sciences 4(2013) 76-85

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P: 33 In Vivo Longitudinal 1H MRS Study of Hippocampal, Cereberal and Striatal Metabolic Changes in the Adult Brain Using an Animal Model of Chronic Hepatic Encephalopathy

The American Journal of Gastroenterology ◽

10.14309/01.ajg.0000582108.29364.13 ◽

2019 ◽

Vol 114 (1) ◽

pp. S17-S17

Author(s):

Dunja Simicic ◽

Katarzyna Pierzchala ◽

Veronika Rackayová ◽

Olivier Braissant ◽

Stefanita-Octavian Mitrea ◽

...

Keyword(s):

Animal Model ◽

Hepatic Encephalopathy ◽

Metabolic Changes ◽

Adult Brain ◽

1H Mrs ◽

Chronic Hepatic Encephalopathy

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To be or not to be pink(1): contradictory findings in an animal model for Parkinson’s disease

Brain Communications ◽

10.1093/braincomms/fcz016 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 2

Author(s):

Ria de Haas ◽

Lisa C M W Heltzel ◽

Denise Tax ◽

Petra van den Broek ◽

Hilbert Steenbreker ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Model ◽

Substantia Nigra ◽

Dopaminergic Neurons ◽

In Vivo Microdialysis ◽

Substantia Nigra Pars Compacta ◽

Laboratory Animals ◽

Motor Deficits

Abstract The PTEN-induced putative kinase 1 knockout rat (Pink1−/−) is marketed as an established model for Parkinson’s disease, characterized by development of motor deficits and progressive degeneration of half the dopaminergic neurons in the substantia nigra pars compacta by 8 months of age. In this study, we address our concerns about the reproducibility of the Pink1−/− rat model. We evaluated behavioural function, number of substantia nigra dopaminergic neurons and extracellular striatal dopamine concentrations by in vivo microdialysis. Strikingly, we and others failed to observe any loss of dopaminergic neurons in 8-month-old male Pink1−/− rats. To understand this variability, we compared key experimental parameters from the different studies and provide explanations for contradictory findings. Although Pink1−/− rats developed behavioural deficits, these could not be attributed to nigrostriatal degeneration as there was no loss of dopaminergic neurons in the substantia nigra and no changes in neurotransmitter levels in the striatum. To maximize the benefit of Parkinson’s disease research and limit the unnecessary use of laboratory animals, it is essential that the research community is aware of the limits of this animal model. Additional research is needed to identify reasons for inconsistency between Pink1−/− rat colonies and why degeneration in the substantia nigra is not consistent.

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D-512 and D-440 as Novel Multifunctional Dopamine Agonists: Characterization of Neuroprotection Properties and Evaluation of In Vivo Efficacy in a Parkinson’s Disease Animal Model

ACS Chemical Neuroscience ◽

10.1021/cn400106n ◽

2013 ◽

Vol 4 (10) ◽

pp. 1382-1392 ◽

Cited By ~ 21

Author(s):

Soumava Santra ◽

Liping Xu ◽

Mrudang Shah ◽

Mark Johnson ◽

Aloke Dutta

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Model ◽

Dopamine Agonists ◽

In Vivo Efficacy

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Calcitriol Alleviates MPP+- and MPTP-Induced Parthanatos Through the VDR/PARP1 Pathway in the Model of Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.657095 ◽

2021 ◽

Vol 13 ◽

Author(s):

Junjie Hu ◽

Jiawei Wu ◽

Fang Wan ◽

Liang Kou ◽

Sijia Yin ◽

...

Keyword(s):

Parkinson’S Disease ◽

Vitamin D ◽

Parkinson's Disease ◽

Animal Model ◽

Cell Model ◽

Dopamine Neurons ◽

Protective Effects ◽

Excessive Activation

The pathogenesis of Parkinson’s disease (PD) is currently unclear. Recent studies have suggested a correlation between vitamin D and PD. Vitamin D and its analogs have protective effects in animal models of PD, but these studies have not clarified the mechanism. Parthanatos is a distinct type of cell death caused by excessive activation of poly (ADP-ribose) polymerase-1 (PARP1), and the activation of PARP1 in PD models suggests that parthanatos may exist in PD pathophysiology. 1,25-Dihydroxyvitamin D3 (calcitriol) is a potential inhibitor of PARP1 in macrophages. This study aimed to investigate whether calcitriol treatment improves PD models and its effects on the parthanatos pathway. A 1-methyl-4-phenylpyridinium (MPP+)-induced cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute animal model were selected as the in vitro and in vivo PD models, and calcitriol was applied in these models. Results showed that parthanatos existed in the MPP+-induced cell model and pretreatment with calcitriol improved cell viability, reduced the excessive activation of PARP1, and relieved parthanatos. The application of calcitriol in the MPTP subacute animal model also improved behavioral tests, restored the damage to dopamine neurons, and reduced the activation of PARP1-related signaling pathways. To verify whether calcitriol interacts with PARP1 through its vitamin D receptor (VDR), siRNA, and overexpression plasmids were used to downregulate or overexpress VDR. Following the downregulation of VDR, the expression and activation of PARP1 increased and PARP1 was inhibited when VDR was overexpressed. Coimmunoprecipitation verified the combination of VDR and PARP1. In short, calcitriol can substantially improve parthanatos in the MPP+-induced cell model and MPTP model, and the protective effect might be partly through the VDR/PARP1 pathway, which provides a new possibility for the treatment of PD.

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