scholarly journals Dual Effects of Human Placenta-Derived Neural Cells on Neuroprotection and the Inhibition of Neuroinflammation in a Rodent Model of Parkinson’s Disease

2018 ◽  
Vol 27 (5) ◽  
pp. 814-830 ◽  
Author(s):  
Han Wool Kim ◽  
Hyun-Seob Lee ◽  
Jun Mo Kang ◽  
Sang-Hun Bae ◽  
Chul Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Placenta ◽  
Precursor Cells ◽  
Rodent Model ◽  
Neural Precursor Cells ◽  
Substantia Nigra Pars Compacta ◽  
Neural Precursor ◽  
Age Related ◽  
Therapeutic Mechanisms

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.

scholarly journals Bioluminescence‐driven optogenetic activation of transplanted neural precursor cells improves motor deficits in a Parkinson's disease mouse model

2018 ◽  
Vol 98 (3) ◽  
pp. 458-468 ◽  
Author(s):  
Jessica R. Zenchak ◽  
Brandon Palmateer ◽  
Nicolai Dorka ◽  
Tariq M. Brown ◽  
Lina‐Marie Wagner ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Motor Deficits ◽  
Neural Precursor

Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson's disease

2003 ◽  
Vol 151 (2) ◽  
pp. 204-217 ◽  
Author(s):  
Richard J. E. Armstrong ◽  
Pamela Tyers ◽  
Meena Jain ◽  
Andrew Richards ◽  
Stephen B. Dunnett ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Ventral Mesencephalon

The Potential for Circuit Reconstruction by Expanded Neural Precursor Cells Explored through Porcine Xenografts in a Rat Model of Parkinson's Disease

2002 ◽  
Vol 175 (1) ◽  
pp. 98-111 ◽  
Author(s):  
Richard J.E. Armstrong ◽  
Carrie B. Hurelbrink ◽  
Pam Tyers ◽  
Emma L. Ratcliffe ◽  
Andrew Richards ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor

scholarly journals Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3459 ◽  
Author(s):  
Sandra Barata-Antunes ◽  
Fábio G. Teixeira ◽  
Bárbara Mendes-Pinheiro ◽  
Ana V. Domingues ◽  
Helena Vilaça-Faria ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Welfare ◽  
Neurodegenerative Disorder ◽  
Negative Impact ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal Pathway ◽  
Aged Rats ◽  
Age Related ◽  
The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

Protein stability and aggregation in Parkinson's disease

2008 ◽  
Vol 413 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Philip A. Robinson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Clinical Symptoms ◽  
Disease Process ◽  
Substantia Nigra Pars Compacta ◽  
Mitochondrial Activity ◽  
Apparent Paradox ◽  
Lewy Neurites ◽  
Age Related

Parkinson's disease (PD), the second most common age-related neurodegenerative disease, results in abnormalities in motor functioning. Many fundamental questions regarding its aetiology remain unanswered. Pathologically, it is not until 70–80% of the dopaminergic neurons from the substantia nigra pars compacta are lost before clinical symptoms are observed. Thus research into PD is complicated by this apparent paradox in that what appears to be the beginning of the disease at the clinical level is really the end point neurochemically. Consequently, we can only second guess when the disease started and what initiated it. The causation is probably complex, with contributions from both genetic and environmental factors. Intracellular proteinaceous inclusions, Lewy bodies and Lewy neurites, found in surviving dopaminergic neurons, are the key pathological characteristic of PD. Their presence points to an inability within these terminally differentiated cells to deal with aggregating proteins. Recent advances in our knowledge of the underlying disease process have come about from studies on models based on genes associated with rare hereditary forms of PD, and mitochondrial toxins that mimic the behavioural effects of PD. The reason that dopaminergic neurons are particularly sensitive may be due to the additional cellular stress caused by the breakdown of the inherently chemically unstable neurotransmitter, dopamine. In the present review, I discuss the proposal that in sporadic disease, interlinked problems of protein processing and inappropriate mitochondrial activity seed the foundation for age-related increased levels of protein damage, and a reduced ability to deal with the damage, leading to inclusion formation and, ultimately, cell toxicity.

Neuroprotective effect of agmatine (decarboxylated l-arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson’s disease

2018 ◽  
Vol 38 (2) ◽  
pp. 173-184 ◽  
Author(s):  
EK El-Sayed ◽  
AAE Ahmed ◽  
EM El Morsy ◽  
S Nofal
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Sprague Dawley Rats

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer’s disease, characterized by loss of dopaminergic neurons in substantia nigra pars compacta, accompanied by motor and nonmotor symptoms. The neuropathological hallmarks of PD are well reported, but the etiology of the disease is still undefined; several studies assume that oxidative stress, mitochondrial defects, and neuroinflammation play vital roles in the progress of the disease. The current study was established to investigate the neuroprotective effect of agmatine on a rotenone (ROT)-induced experimental model of PD. Adult male Sprague Dawley rats were subcutaneously injected with ROT at a dose of 2 mg/kg body weight for 35 days. Agmatine was injected intraperitoneally at 50 and 100 mg/kg body weight, 1 h prior to ROT administration. ROT-treated rats that received agmatine showed better performance on beam walking and an elevated number of rears within the cylinder test. In addition, agmatine reduced midbrain malondialdehyde as an indication of lipid peroxidation, pro-inflammatory cytokines including tumor necrosis factor alpha and interleukin-1β, and glial fibrillary acidic protein. Moreover, agmatine was responsible for preventing loss of tyrosine hydroxylase-positive neurons. In conclusion, our study showed that agmatine possesses a dose-dependent neuroprotective effect through its antioxidant and anti-inflammatory activities. These findings need further clinical investigations of agmatine as a promising neuroprotective agent for the future treatment of PD.

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