Does levodopa affect endogenous and exogenous dopaminergic neuron survival?

Song, Mengru 2022. Does levodopa affect endogenous and exogenous dopaminergic neuron survival? PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Parkinson’s disease is a progressive neurodegenerative disease that has no cure to date. Fortunately, stem cell replacement therapy has now become a promising option that has the potential to greatly restore patient’s motor function. However, efforts have to be paid to understand if current golden standard L-DOPA treatment will have negative impact on the novel therapy. Therefore, this study aims to evaluate the effects of L-DOPA on endogenous and exogenous dopaminergic cells. To evaluate endogenous dopaminergic cells, the classical 6-OHDA rat model was used. The L-DOPA treatment plan was adjusted to more closely represent the clinical experiences of PD patients. Behavior and immunohistochemistry analysis were conducted for the evaluation of the results. Overall, L-DOPA treatment showed no negative influences on endogenous dopaminergic neuron survival. Next, the 6-OHDA model was used to observe if long-term L-DOPA treatment influences the survival of exogenous human grafts. Again, the treatment plan attempted to more closely represent the real situation, which includes the proper use of immunosuppressant and its withdrawal. The results reflected that L-DOPA did not negatively influence exogenous dopaminergic neurons in the absence of immunosuppression. Lastly, an improved α-synuclein overexpression plus preformed α-synuclein fibril model was used, allowing the progressive features of PD to be reproduced. This model still aimed to evaluate the impact of L-DOPA on the endogenous dopaminergic neurons, but it provides more information about the interplay between L-DOPA and the neurodegenerative feature of PD. Overall, the results still indicated that L-DOPA has no negative impact on the dopaminergic neuron survival. In conclusion, L-DOPA showed no detrimental effects to endogenous and exogenous dopaminergic neuron survival in any of these rat models mentioned above and this provides valuable information for further studies in this aspect.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	1 March 2023
Last Modified:	01 Mar 2024 02:30
URI:	https://orca.cardiff.ac.uk/id/eprint/156963

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