Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies

2016 ◽  
Vol 55 (01) ◽  
pp. 21-28 ◽  
Author(s):  
C. Antke ◽  
H. Hautzel ◽  
H.-W. Mueller ◽  
S. Nikolaus
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Sites ◽  
Human Subjects ◽  
Synaptic Cleft ◽  
Presynaptic Terminal ◽  
Imaging Studies ◽  
Psychiatric Conditions ◽  
Da Release

SummaryNumerous neurologic and psychiatric conditions are treated with pharmacological compounds, which lead to an increase of synaptic dopamine (DA) levels. One example is the DA precursor L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted to DA in the presynaptic terminal. If the increase of DA concentrations in the synaptic cleft leads to competition with exogenous radioligands for presynaptic binding sites, this may have implications for DA transporter (DAT) imaging studies in patients under DAergic medication.This paper gives an overview on those findings, which, so far, have been obtained on DAT binding in human Parkinson’s disease after treatment with L-DOPA. Findings, moreover, are related to results obtained on rats, mice or non-human primates. Results indicate that DAT imaging may be reduced in the striata of healthy animals, in the unlesioned striata of animal models of unilateral Parkinson’s disease and in less severly impaired striata of Parkinsonian patients, if animal or human subjects are under acute or subchronic treatment with L-DOPA. If also striatal DAT binding is susceptible to alterations of synaptic DA levels, this may allow to quantify DA reuptake in analogy to DA release by assessing the competition between endogenous DA and the administered exogenous DAT radioligand.

In vivo imaging neurotransmitter function

2011 ◽  
Vol 50 (04) ◽  
pp. 155-156 ◽  
Author(s):  
R. Larisch ◽  
H. Vosberg ◽  
M. Beu ◽  
H. Hautzel ◽  
A. Wirrwar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
In Vivo Imaging ◽  
Clinical Studies ◽  
Small Animal Imaging ◽  
Small Animal ◽  
Imaging Studies ◽  
Animal Imaging

SummaryThis article gives an overview of those small animal imaging studies which have been conducted on neurotransmitter function in the rat 6-hydoxydopamine (6-OHDA) model of Parkinson’s disease, and discusses findings with respect to the outcome of clinical studies on Parkinsonian patients.

In vivo multimodal (MRI, SPECT) imaging of the 6-OHDA rat model for Parkinson's disease correlated with behavior and histology

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S392-S392
Author(s):  
Nadja Van Camp ◽  
Koen Van Laere ◽  
Ruth Vreys ◽  
Marleen Verhoye ◽  
Erwin Lauwers ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Spect Imaging ◽  
Multimodal Mri

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals Effectiveness and mechanisms of adipose-derived stem cell therapy in animal models of Parkinson’s disease: a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Keya Li ◽  
Xinyue Li ◽  
Guiying Shi ◽  
Xuepei Lei ◽  
Yiying Huang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Therapeutic Option ◽  
Meta Analysis ◽  
Future Application ◽  
Neuroprotective Effects ◽  
Standard Mean Difference ◽  
Study Characteristics

AbstractAnimal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells (ADSCs). Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease (PD). Here, eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention. Quality assessment was conducted using a 10-item risk of bias tool. For the subsequent meta-analysis, study characteristics were extracted and effect sizes were computed. Ten out of 2324 published articles (n = 169 animals) were selected for further meta-analysis. After ADSC therapy, the rotation behavior (10 experiments, n = 156 animals) and rotarod performance (3 experiments, n = 54 animals) were improved (P < 0.000 01 and P = 0.000 3, respectively). The rotation behavior test reflected functional recovery, which may be due to the neurogenesis from neuronally differentiated ADSCs, resulting in a higher pooled effect size of standard mean difference (SMD) (− 2.59; 95% CI, − 3.57 to − 1.61) when compared to that of primitive cells (− 2.18; 95% CI, − 3.29 to − 1.07). Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect. Following the transplantation of ADSCs, tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36 [6.85, 19.86]. Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD. The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects. The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

scholarly journals Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Shelby Shrigley ◽  
Fredrik Nilsson ◽  
Bengt Mattsson ◽  
Alessandro Fiorenzano ◽  
Janitha Mudannayake ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Functional Recovery ◽  
Embryonic Stem ◽  
Hesc Line ◽  
Alternative Source ◽  
And Function

Background: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. Objective: To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Methods: Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitro or transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Results: Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. Conclusion: This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

scholarly journals Neuroprotective Effect of Optimized Yinxieling Formula in 6-OHDA-Induced Chronic Model of Parkinson’s Disease through the Inflammation Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Renrong Wei ◽  
Cuiping Rong ◽  
Qingfeng Xie ◽  
Shouhai Wu ◽  
Yuchao Feng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Binding ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Cox 2

Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN)-striatum circuit, which is associated with glial activation and consequent chronic neuroinflammation. Optimized Yinxieling Formula (OYF) is a Chinese medicine that exerts therapeutical effect and antiinflammation property on psoriasis. Our previous study has proven that pretreatment with OYF could regulate glia-mediated inflammation in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Given that PD is a chronic degeneration disorder, this study applied another PD animal model induced by striatal injection of 6-hydroxydopamine (6-OHDA) to mimic the progressive damage of the SN-striatum dopamine system in rats. The OYF was administrated in the manner of pretreatment plus treatment. The effects of the OYF on motor behaviors were assessed with the apomorphine-induced rotation test and adjusting steps test. To confirm the effect of OYF on dopaminergic neurons and glia activation in this model, we analyzed the expression of tyrosine hydroxylase (TH) and glia markers, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP) in the SN region of the rat PD model. Inflammation-associated factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were further evaluated in this model and in interferon-γ- (INF-γ-) induced murine macrophages RAW264.7 cells. The results from the in vivo study showed that OYF reversed the motor behavioral dysfunction in 6-OHDA-induced PD rats, upregulated the TH expression, decreased the immunoreactivity of Iba-1 and GFAP, and downregulated the mRNA levels of TNF-α and COX-2. The OYF also trended to decrease the mRNA levels of IL-1β and iNOS in vivo. The results from the in vitro study showed that OYF significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. Therefore, this study suggests that OYF exerts antiinflammatory effects, which might be related to the protection of dopaminergic neurons in 6-OHDA-induced chronic neurotoxicity.

Sensitive and accurate determination of neurotransmitters from in vivo rat brain microdialysate of Parkinson's disease using in situ ultrasound-assisted derivatization dispersive liquid–liquid microextraction by UHPLC-MS/MS

RSC Advances ◽  
2016 ◽  
Vol 6 (110) ◽  
pp. 108635-108644 ◽  
Author(s):  
Xian-En Zhao ◽  
Yongrui He ◽  
Ping Yan ◽  
Na Wei ◽  
Renjun Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Brain ◽  
Accurate Determination ◽  
Ultrasound Assisted ◽  
Dispersive Liquid Liquid Microextraction ◽  
Liquid Microextraction

In situ UA-DDLLME coupled with UHPLC-MS/MS has been developed for simultaneous determination of neurotransmitters and baicalein from Parkinson's disease rats.

Simvastatin Prevents Neurodegeneration in the MPTP Mouse Model of Parkinson’s Disease via Inhibition of A1 Reactive Astrocytes

2021 ◽  
pp. 1-8
Author(s):  
Ren-Wei Du ◽  
Wen-Guang Bu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Underlying Mechanism ◽  
Reactive Astrocytes ◽  
Dopamine Neurons ◽  
Neuron Death ◽  
Neurologic Disorders

Emerging evidence indicates that A1 reactive astrocytes play crucial roles in the pathogenesis of Parkinson’s disease (PD). Thus, development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat PD. Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and primary astrocytes/neurons were prepared to investigate the effects of simvastatin on PD and its underlying mechanisms in vitro and in vivo. We show that simvastatin protects against the loss of dopamine neurons and behavioral deficits in the MPTP mouse model of PD. We also found that simvastatin suppressed the expression of A1 astrocytic specific markers in vivo and in vitro. In addition, simvastatin alleviated neuron death induced by A1 astrocytes. Our findings reveal that simvastatin is neuroprotective via the prevention of conversion of astrocytes to an A1 neurotoxic phenotype. In light of simvastatin favorable properties, it should be evaluated in the treatment of PD and related neurologic disorders characterized by A1 reactive astrocytes.

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