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Identification of dopamine 'mother cells' could lead to future Parkinson's treatments
April 08, 2008
'Mother cells' which produce the neurons affected by Parkinson's disease have been identified by scientists, according to new research published in the journal Glia. The new discovery could pave the way for future treatments for the disease, including the possibility of growing new neurons, and the cells which support them, in the lab. Scientists hope these could then be transplanted into patients to counteract the damage caused by Parkinson's.
The new study focuses on dopaminergic neurons - brain cells which produce and use the chemical dopamine to communicate with surrounding neurons. The researchers found that these important neurons are created when a particular type of cell in the embryonic brain divides during the early stages of brain development in the womb.
If a person suffers from Parkinson's disease, it is the depletion of these dopaminergic neurons and the associated lack of dopamine in the body which causes chronic and progressive symptoms including tremors, stiff muscles and slow movement.
The international research team used mouse models in the laboratory to examine the early stages of brain formation. They discovered that dopaminergic neurons are formed by precursor cells identified as 'radial glia-like cells' by the scientists because of their similarity to radial glia cells which are already known to build other parts of the brain.
The scientists hope that this discovery could, in the future, lead to new therapies which would use these radial glia-like cells derived from patients' own stem cells to grow replacement neurons in the lab, which could then be transplanted into the brain to replace the neurons they have lost.
One of the authors of the paper, Dr Anita Hall from Imperial College London's Department of Life Sciences, explains the potential of the team's findings: "You could call these radial glia-like cells the stem cells of this part of the brain - they contain all the information needed to create and support the young dopamine-producing neurons which are essential for important human functions including motor activity, cognition and some behaviours.
"Now that we understand how these neurons are produced, we hope that this knowledge can be used to develop novel therapies including techniques to create replacement neurons for people with Parkinson's which could be implanted into the brain to bolster their vital supplies of dopamine."
Dr Hall adds, however, that more research is needed to work out how exactly these glia-like cells could be used: "Using these mother cells to grow new neurons in the lab which are fit to be transplanted into humans will be complicated, and extensive further research is needed before this becomes a clinical reality. For example, we're not yet sure whether the mother cells themselves would need to be transplanted too, in order to facilitate successful dopamine production in the brain of a Parkinson's patient," she said.
In the UK, one in every 500 people - approximately 120,000 individuals - has Parkinson's disease. Around 10,000 people are diagnosed with the disease every year. The symptoms of Parkinson's disease usually appear when about 80% of the brain's dopamine has been lost. The level of dopamine in the brain then continues to fall slowly over many years. The reasons why the loss of dopamine occurs in the brains of people with Parkinson's is currently unknown.
Imperial College London
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Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra (Journal of Neural Transmission. Supplementa)
by Giuseppe Di Giovanni (Editor), Vincenzo Di Matteo (Editor), Ennio Esposito (Editor)
This book provides a unique and timely multidisciplinary synthesis of our current knowledge of the anatomy, pharmacology, physiology and pathology of the substantia nigra pars compacta (SNc) dopaminergic neurons. The single chapters, written by top scientists in their fields, explore the life cycle of dopaminergic neurons from their birth to death, the cause of Parkinson's disease, the second most common and disabling condition in the elderly population. Nevertheless, the intracellular cascade of events leading to dopamine cell death is still unknown and, consequently, treatment is symptomatic rather than preventive. The mechanisms by which alterations cause neuronal death, new therapeutic approaches and the latest evidence of a possible de novo neurogenesis in the SNc are reviewed and...
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Dopaminergic Neuron Transplantation in the Weaver Mouse Model of Parkinson's Disease (Advances in Experimental Medicine and Biology)
by Lazaros C. Triarhou (Author)
This book is the culmination of fifteen years of research on the transplantation of dopaminergic neurons in the striatum of the weaver mouse (wv/wv), a neurological mutant characterized by genetically-determined degeneration of midbrain dopamine neurons. This mutant constitutes the only available laboratory model with a chronic disorder that mimics Parkinson's disease. Structural and functional aspects of intrastriatal mesencephalic neuron grafting into the weaver model are reviewed, including histochemical correlates of graft survival and integration, numerical aspects of donor cell survival, ultrastructural findings on synaptogenesis, neurochemical indices of dopamine uptake and receptor binding, gene expression of structural and neurotransmitter-receptor related molecules,...
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Development of Dopaminergic Neurons (Neuroscience Intelligence Unit)
by Umberto Di Porzio (Editor), Roberto Pernas-Alonso (Editor), Carla Perrone-Capano (Editor)
The catecholamine dopamine (DA) plays a key role in the physiology of most vertebrate and invertebrate organisms. In addition to its role as a transmitter in the nervous system, it has a role in development. The relatively few DA neurons in the mammalian brain have important roles in many neural functions including fine motor integration, neuroendocrine hormone release, cognition, emotive behaviors, male sexual behavior and possibly memory. Considerable information has been accumulated on the complex mechanisms of midbrain patterning, dopamine phenotype induction and maturation and the role of epigenetic factors in speciation, development and maintenance of midbrain dopaminergic function. Among other issues, this book describes the molecular and morphological events required for the...
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![A computational model of sequential movement learning with a signal mimicking dopaminergic neuron activities [An article from: Cognitive Systems Research]](http://ecx.images-amazon.com/images/I/41FWP1RKRDL._SL160_.jpg)
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A computational model of sequential movement learning with a signal mimicking dopaminergic neuron activities [An article from: Cognitive Systems Research]
by W. Li (Author), J. Li (Author), J.D. Johnson (Author)
This digital document is a journal article from Cognitive Systems Research, published by Elsevier in . The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.
Description: We present a computational model of approach learning in a simulated maze environment. Our maze environment and training method mimics those used in the experimental literature. We show that our model learns the correct sequence of six decisions that lead to the location of positive reinforcement and in a manner consistent with experimental observations. Our model exhibits many properties that are characteristic of animal learning in maze environments including delay conditioning, secondary conditioning, and...
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Nonstriatal dopaminergic neurons (Advances in biochemical psychopharmacology)
by Erminio Costa (Author), G. L. Gassa (Author)
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Parkinson's Disease: The Life Cycle of the Dopamine Neuron (Annals of the New York Academy of Sciences)
by Howard J. Federoff (Editor)
Parkinson's Disease (PD), a progressive neurological disorder arising from degeneration of dopaminergic neurons in the substantia nigra region of the brain, is characterized by impairment of movement control. It progresses from symptoms such as tremor and muscle rigidity to total disability and death. This study focuses on the dopaminergic system from a developmental perspective, with the objective of improving the understanding of how dopaminergic neurons form, how they mature and respond to genetic and environmental factors, and how they may be regenerated.
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Development and Engineering of Dopamine Neurons (Advances in Experimental Medicine and Biology)
by R. Jeroen Pasterkamp (Editor), Marten P. Smidt (Editor), J. Peter H. Burbach (Editor)
The neurotransmitter dopamine has just celebrated its 50th birthday. The discovery of dopamine as a neuronal entity in the late 1950’s and the notion that it serves in neurotransmission has been a milestone in the field of neuroscience research. This milestone marked the beginning of an era that explored the brain as an integrated collection of neuronal systems that one could distinguish on basis of neurotransmitter identities, and importantly, in which one started to be able to pinpoint the seat of brain disease. The mesodiencephalic dopaminergic (mdDA) system, previously designated as midbrain dopaminergic system, has received much attention since its discovery. The initial identification of dopamine as a neurotransmitter in the central nervous system (CNS) and its...
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The Role of KATP Channels in Models of Midbrain Dopaminergic Neuron Loss: Open Probability Influences Neuron Survival in Vitro
by Christian Scholz (Author)
The dopaminergic neurons of the ventral midbrain (mesDA neurons) form several distinct sub-populations which are involved in emotional control, reward behaviour and motor control. In patients with Parkinson's Disease, the dopaminergic neurons of the substantia nigra, pars compacta (SNpc) gradually die. One focus of research has been to find an explanation why the SNpc neurons are more vulnerable to cellular stress than other neuronal populations. KATP channels consist of Sur1 or 2 and Kir6.1 or 6.2 subunits and link the metabolic state of a cell to its membrane potential. Hypothetically, the normal open-closed state of KATP channels might influence cellular survival when the mesDA neurons are under oxidative stress. In this work, I show that blocking KATP channels in vitro by...
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Nonstriatal Dopaminergic Neurons. Advances in Biochemical Psychopharmacology Volume 16
by Erminio & Gessa, G. L., eds Costa (Author)
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Dopaminergic Neuron Transplantation in the Weaver Mouse Model of Parkinson's Disease
by Lazaros C. Triarhou (Author)
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