Real-Time Dynamics of Dopamine Released from Neuronal Transplants in Experimental Parkinson's Disease

  title={Real-Time Dynamics of Dopamine Released from Neuronal Transplants in Experimental Parkinson's Disease},
  author={Stephanie J. Cragg and Deborah J. Clarke and Susan A. Greenfield},
  journal={Experimental Neurology},
Intrastriatal transplantation of foetal midbrain dopamine (DA) neurons ameliorates the fundamental symptoms of dopaminergic denervation in clinical and experimental parkinsonism despite providing only restricted reinnervation. To understand how DA function is restored by these grafts we used fast-scan cyclic voltammetry at a carbon-fiber microelectrode in vitro to monitor directly and in "real time" the dynamics of graft-derived DA. Simulations of Michaelis-Menten kinetics were used to model… 
Dopamine Release and Uptake Dynamics within Nonhuman Primate Striatum In Vitro
Heterogeneity demonstrated within the primate putamen in the availability and dynamic regulation of DA may be central to understanding DA function in health, cocaine abuse, and disease.
Striatal dopamine neurotransmission: regulation of release and uptake.
Dyskinesias and Neural Grafting in Parkinson's Disease
Results from early openlabel clinical trials showed that embryonic VM tissue can engraft in the parkinsonian striatum and provide a local source of DA storage and release, and suggested that neural cell replacement could develop into a radically new treatment approach for a wide range of neurological disorders.
Persistent Dopamine Functions of Neurons Derived from Embryonic Stem Cells in a Rodent Model of Parkinson Disease
After transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects, suggesting that ES cell‐derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation.
Diffusion parameters in the striatum of rats with 6‐hydroxydopamine‐induced lesions and with fetal mesencephalic grafts
Investigation of the diffusion parameters of the extracellular space in the striatum of control, 6‐hydroxydopamine‐lesioned, intrastriatally grafted, and sham‐grafted rats in vivo found multiple but smaller graft deposits impair the conditions for diffusion and extrasynaptic transmission.
Amphetamine induced rotation in the assessment of lesions and grafts in the unilateral rat model of Parkinson's disease
Differential time‐course profiles of dopamine release and uptake changes induced by three dopamine uptake inhibitors
The time‐course mismatch between uptake inhibition and DA release potentiation as well as release rebound during washout suggests that altered dopamine release might play a role in behavioral effects of cocaine.


Characteristics of electrically evoked somatodendritic dopamine release in substantia nigra and ventral tegmental area in vitro.
The findings that somatodendritic release was frequency dependent across a range characteristic of DA cell firing rates and that stimulated [DA]o varied markedly among DA cell body regions have important implications for how dendritically released DA may function in the physiology and pathophysiology of substantia nigra and VTA.
Neural transplantation in Parkinson's disease.
  • O. Lindvall
  • Medicine, Biology
    Novartis Foundation symposium
  • 2000
Recent findings using positron emission tomography indicate that the grafts are functionally integrated in the patient's brain and release dopamine into the striatum, indicating long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment.
Restoration of dopamine overflow and clearance from the 6-hydroxydopamine lesioned rat striatum reinnervated by fetal mesencephalic grafts.
The behavioral improvements by grafts of fetal mesencephalic tissue are accompanied by morphological and electrochemical evidence of reinnervation and the restoration of DA input, suggesting that measurement of DA clearance may reveal a wider area ofReinnervation than that indicated by more traditional immunocytochemical methods.
Effect of Prior Dopamine Denervation on Survival and Fiber Outgrowth from Intrastriatal Fetal Mesencephalic Grafts
It is demonstrated that the mature neostriatal tissue can support axonal growth and innervation from grafted fetal DA neurons even in the presence of a normal complement of endogenous DA fibers.