Chapter category: Neurodegenerative Disease
Directions for Future Research
Dopaminergic Neuron Transplantation in the Weaver Mouse Model of Parkinson's Disease
Edited by: Lazaros TriarhouISBN: 0-306-47435-2
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Chapter authors:
Lazaros C. Triarhou
Our groundwork, first, introduced and characterized in detail the weaver mouse as a model of spontaneous progressive dopamine (DA) deficiency similar to Parkinson's disease, and secondly, laid the foundations for the intracerebral transplantation of catecholamine-producing neurons in this model of degeneration. Weaver mice represent the only known model of genetically-determined degeneration of the endogenous DA system and offer a unique opportunity to study the effects of a chronically ill environment on the fate of grafted DA neurons.
Summarizing the previous Chapters, one can emphasize the following essential points. The weaver mutation leads to a progressive degeneration of nigrostriatal DA neurons over the animal's life-span: 40% of nigral DA cells are lost during the first three postnatal weeks, an additional 30% by three months of age, and another 15% during the second year of life.1,2 Moreover, there is a 22% loss of striatal medium-sized neurons in one-year old animals.3
Neural transplantation studies show that fetal DA-rich grafts prepared from wild-type mouse donors survive after implantation into the weaver striatum and express many normal histochemical properties; supply an axonal and a dendritic innervation to host tissue and establish synaptic connections with host striatal neurons; lead to increases in DA uptake parameters; bring about a functional recovery, evidenced by induction of a contralateral rotational asymmetry after unilateral grafts and by an enhancement of locomotor performance after bilateral transplantation. However, grafts seem to do better in the surviving DA neuron number when implanted into wild-type (+/+) host mice with nigral 6-hydroxydopamine (6-OHDA) lesions, compared to weaver hosts.
In Parkinson's disease, the progressive degeneration of nigral neurons occurs over many years. It is conceivable that in Parkinsonian patients receiving neural grafts, the ongoing disease process might destroy donor DA neurons.4 The question as to whether one example of a disease process interferes with the survival of grafted neurons can be addressed in transplantation studies in weaver mice. Further studies could look into factors that may be responsible for the vulnerability of grafted DA cells in the chronically ill weaver environment, and determine whether or not experimental manipulations can optimize graft performance.
Additional chapters from this book:
Directions for Future Research
Lazaros C. Triarhou
Our groundwork, first, introduced and characterized in detail the weaver mouse as a model of spontaneous progressive dopamine (DA) deficiency similar to Parkinson's disease, and secondly, l...
Behavioral Recovery of Functional Responses
Lazaros C. Triarhou
Studies in rats have shown that unilateral destruction of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) results in a spontaneous rotational bias to the side ipsilateral to the les...
Neurochemical Indices of Functional Restoration
Lazaros C. Triarhou
A general asset of the weaver model is that one can study graft development at the same time as the animal's own dopamine (DA) system continues to undergo a progressive degeneration, which is ...
Structural Correlates of Process Outgrowth and Circuit Reconstruction
Lazaros C. Triarhou
Certain cellular mechanisms by which grafts promote recovery in experimental animals have been deciphered.1,2 It has been suggested that a multitude of trophic, neurohumoral and ...
Histochemical Properties of Intrastriatal Mesencephalic Grafts
Lazaros C. Triarhou
The rationale behind neural transplantation studies using the weaver mouse model has been to replace degenerated neurons that are lost in the neurogenetic disease by intracerebrally grafted fe...
Biology and Pathology of the Weaver Mutant Mouse
Lazaros C. Triarhou
The weaver mutant mouse (wv/wv) is characterized by a genetically-induced degeneration of mesostriatal dopamine (DA) neurons. In that sense, it can be viewed as a pathophysiological phenoco...
Introduction
Lazaros C. Triarhou
Dopamine and Parkinson's Disease
Movement control is accomplished by complex interactions among various groups of nerve cells in the central nervous system. One such important group ofneurons...
