Physiological Restoration and In Vivo Neurochemistry�Physiology and Pharmacology of Dopaminergic and Serotoninergic Neurotransmission of Striatum in Animal Models of Parkinson’s Disease

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Dr. Aygul Balcioglu
Harvard Medical School
Massachusetts

Abstract

Currently, we are interested in characterizing how serotoninergic neurotransmission is affected in animal models of Parkinson’s disease as it seems that co-expression of serotoninergic phenotypes after transplantation might also contribute to benefits seen after neural transplantation in Parkinson’s disease. In addition, in normal condition striatum also receives serotoninergic projections from raphe nucleus in addition to the dopaminergic projections from substantia nigra. We propose to study the dopaminergic and serotoninergic neurotransmission in the rat striatum under basal conditions and in Parkinsonian animal models using microdialysis and MRI/MRS of the lesioned rat striatum in terms of its response to the pharmacological challenges such as potassium, tetrodotoxin, apomorphine and amphetamine. In addition to the stimulation of dopaminergic receptors, apomorphine can also increase serotoninergic neurotransmission. Similarly, amphetamine might also increase serotonin levels. This outcome by these two drugs might also contribute to the turning behavior, or else it might explain differences between animals which do not show similar turning even though they receive the same kind of lesion. Another aspect of our study of dopamine and serotonin transmission in Parkinson’s models is the fact that our laboratory showed that ES cells can be differentiated into dopaminergic and serotoninergic phenotypes, suggesting that serotoninergic phenotypes might also contribute to the outcome of transplantation. In addition, striatum also receives serotoninergic projects from raphe nucleus under normal conditions. Currently, we are investigating, using microdialysis and MRI/MRS, how serotoninergic neurotransmission, along with dopaminergic neurotransmission, contributes to behavioral recovery in PD transplantation models.

Progress Report (as of 8/2002)

Our study of dopamine and serotonin neurons in Parkinson’s models using embryonic stem (ES) cells showed that ES cells can be differentiated into dopaminergic and serotoninergic phenotypes. Currently, we are investigating, using cell culture and MRI/MRS, how dopaminergic neurotransmission, along with other transmitter systems and circuitry, contributes to behavioral recovery in PD transplantation models.

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