Neuronal Cells as an Ideal Model for Neurodegenerative Diseases (original) (raw)
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Rat models of major neurodegenerative disorders
OAE Publishing Inc., 2022
No single animal model can recapitulate all the features of a particular human disease on its own. Historically, rats have been used to study neurobiology and underlying functional networks. Likewise, rat models have been created to study neurodegenerative mechanisms and therapeutic interventions. In the last decades, a shift towards the use of mice has been observed in many research fields, not least because of the comparatively easier genetic manipulation of mice. However, with the full sequence of the rat genome being available, advances in genetic manipulation of the rat, and advanced test regimens and biomarkers at hand, the rat presents itself once more as a valuable model organism for studying neurodegenerative disorders. This review provides an overview of currently available, well-characterized rat models of Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as their advantages for studying neurodegenerative disorders and evaluating therapeutic interventions.
A Review on Neurodegenerative Diseases with their Suitable Animal Models
Biosciences Biotechnology Research Asia
Neurodegeneration is one of the common disease conditions globally. The animal models give resemblance to these disease conditions. By using various animal models it can be easy to study the disease in detail with their pathology, history, mechanism of drug. Animal models are crucial for researchers to find out preventing measures of neurodegenerative diseases. The intention of writing this review paper is to give a brief idea about neurodegenerative disorder and the possible animal models that are recently in use with their short introduction. This paper also explains the future expected animal model that should overcome the previous model’s lacuna. Neurodegeneration is a global health concern now. So to study disease pathology and finding advanced therapy is a challenge. For thorough understanding of this condition there are various animal models that provide deep information at molecular and cellular level. The genetic models are also present that mainly concern for mutation and ...
Journal of Cellular Biotechnology, 2017
BACKGROUND: Major pathomechanisms underlying neurodegenerative diseases, such as Parkinson's Disease, are still not well understood. Induced human pluripotent and rodent embryonic stem cells provide powerful disease models to address neurodegeneration-inducing pathomechanisms on a molecular and cellular level. OBJECTIVE: Our aim is to establish a refined protocol to generate healthy and patient donor stem cell-derived dopaminergic neurons to investigate neurodegenerative events in vitro. METHODS: Human healthy donor-and patient-derived induced pluripotent stem cells were differentiated into stable dopaminergic progenitor cell lines and further differentiated into dopaminergic neurons. Induced pluripotent stem cells, neuronal progenitors and terminally differentiated neurons were characterized by confocal laser microscopy-based immunofluorescence analysis, live cell imaging demonstrating dopamine transporter-specific uptake of a fluorescent substrate and transcriptome analysis. RESULTS: Based on our immunofluorescence analysis, dopaminergic differentiation approaches predominantly yield dopaminergic neurons and GFAP-expressing glial cells. We detected a small partition of GABAergic neurons, yet neither serotonergic nor glutamatergic neurons. Dopaminergic neurons were successfully stained for pre-and postsynaptic and mitochondrial markers. Live cell imaging experiments verified dopamine transporter-dependent uptake of the fluorescent monoamine transporter substrate ASP+. CONCLUSION: Human stem cell-derived dopaminergic neurons are a suitable cellular system for fluorescence-based experimental approaches to address neurodegenerative events in vitro.
Immortalized Dopamine Neurons: A Model to Study Neurotoxicity and Neuroprotection
Proceedings of the Society for Experimental Biology and Medicine, 1999
6-Hydroxydopamine (6-OHDA) causes selective degeneration of dopaminergic neurons in the rat brain and has been used to produce an animal model of Parkinsonism. Recently, a clonal line of immortalized dopamine (DA) neurons (1RB 3 AN 27 ), which expresses varying levels of tyrosine hydroxylase, dopamine transporter, neuron specific enolase, and nestin, was established. These DA neurons reduce behavioral deficits in 6-OHDA-lesioned rats. The relative sensitivity of fetal and adult neurons to potential neurotoxins is not well defined. The availability of immortalized DA neurons provides a unique opportunity to compare the relative neurotoxicity of 6-OHDA in differentiated and undifferentiated DA neurons in vitro and identify neuroprotective agents. Our results showed that 6-OHDA treatment for 24 hr decreased the viability of undifferentiated and differentiated immortalized DA neurons in vitro, as determined by the MTT assay, and increased the rate of apoptosis in differentiated DA neurons. The differentiated DA neurons (IC 50 = 33 µM) were about 2-fold more sensitive to 6-OHDA than undifferentiated DA neurons (IC 50 = 75 µM) in cell culture. Similarly, the differentiated DA neurons were more sensitive to another neurotoxin, 1-methyl-4-phenylpyridinium (MPP + ), which is commonly used to induce Parkinsonism in animal models, than were the undifferentiated DA neurons in culture. Among growth factors tested, only glial cell line-derived neurotrophic factor (GDNF) partially protected differentiated DA neurons against 6-OHDA-induced toxicity. These results suggest that undifferentiated and differentiated immortalized DA neurons can be a useful experimental model to study relative sensitivity to neurotoxins and neuroprotective agents that could have relevance to fetal and adult neurons.
IAR Journal of Medical Case Reports, 2021
The term neurodegenerative refers to diseases that are usually recognized by symptoms like decreased motor control, mood disorders, an d cognitive deficits. Some of the common neurodegenerative diseases are Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and the spinocerebellar ataxias. These diseases are complex and diverse in their pathophysiology with some causing memory and cognitive impairments and others affecting a person's ability to move, speak, control, and breathe. T here are some prevalent drugs and therapies, which seems to be effective in improving the disease condition. Thus, It is need of the hour to develop new and more effective therapeutic approaches and strategies to manage and potentially tackle these devastating neurodegenerative diseases.
Dopamine Receptors and Neurodegeneration
Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson's disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases.
Biomedicines
Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells in...
Experimental Neurology, 2001
In an attempt to find a convenient rat model to study cell vulnerability in Parkinson's disease, we have investigated the cell-loss profile in different midbrain dopaminergic nuclei and subnuclei of rats injected with 6-hydroxydopamine (6-OHDA) in the third ventricle. Following administration of different doses (5-1000 g) of 6-OHDA, motor behavior was evaluated and tyrosine hydroxylase-immunostained neurons were counted in the A8 group and different subdivisions of A9 and A10 groups. Animals developed hypokinesia, repetitive chewing movements, and catalepsia. Signs of cell degeneration were evident from the first day after injection, reaching the definitive pattern at the end of the first week. There was a similar degeneration in both brain sides, the A9 group showing the highest degree of cell-loss, followed by A8 and A10 groups. In the A9 group, the degeneration mostly affected those subgroups located in its ventral, lateral, and posterior regions. In the A10 group the degeneration mainly affected the parabrachial pigmented nucleus, the paranigral nucleus and the ventral tegmental area. This topographic pattern of degeneration is very similar to that previously described in Parkinson's disease, suggesting that this model may be a useful tool in the study of the cell vulnerability mechanisms in this neurodegenerative disorder. In addition, our results also showed that small dopaminergic neurons are more resistant to degeneration than the large ones. In some DA subgroups, the cells that contained calbindin but not calretinin were less vulnerable to the neurotoxic effect of 6-OHDA.