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SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE

Bhatt, Sandeep
http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349

Abstract Details

2006, PHD, Kent State University, College of Biomedical Sciences.
Parkinson’s disease (PD) is a neurodegenerative disease that ranks among the most common late life neurodegenerative diseases, affecting approximately 1.5% to 2.0% of the population older than age 60. PD is among the top 15 leading causes of death. There are gender differences in the prevalence of Parkinson's disease with males typically showing a higher incidence. As PD progresses, men exhibit more severe parkinsonian motor features and women experience more L-dopa-induced dyskinesia. The gender differences observed in PD are significant; they can provide some potential hints regarding the etiology of this condition. Moreover, similar gender differences are also observed in the lab experiments when using animals to study the effect of neurotoxins on the NSDA system. In this study I have tried to delineate the differences that exist in the dopamine (DA) reuptake pathways in male and female mice in an attempt to better understand these differences. From the results of the experiments conducted it was seen that the DA reuptake was higher from the synaptic space via the Dopamine Transporter (DAT) and the cytoplasm via the Vesicular Monoamine Transporter 2 (VMAT2) within female mice. It was also seen that the metabolism of DA into DOPAC was favored within male mice. This gender specific profile of DA being re-sequestered into the vesicles within the female mice and the DA being metabolized to DOPAC in the male mice was changed when DAT was blocked pharmacologically using Nomifensine and also when DAT was reduced in numbers via genetic knockdown. Upon DAT inhibition the VMAT2 function was also inhibited and the reuptake of DA was reduced leading to an increased production of DOPAC within the cytoplasm. This effect was stronger within female mice than male mice. These results demonstrated that the DAT-VMAT2 interaction with the mice dopaminergic neurons showed gender specific differences and the inhibition of DAT inhibition dependant VMAT2 inhibition also showed gender specific effects. The interactions between DAT and VMAT2 are thought to mediate vulnerability to neurotoxins and the pathogenesis of PD. It is possible that pharmacological intervention aimed at these transporters in the future might be beneficial in Parkinson’s disease.
Dean Dluzen (Advisor)
140 p.
Parkinson's Disease; Dopamine Transporter; Vesicular Monoamine Transporter 2; Neurodegeneration

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Citations

  • Bhatt, S. (2006). SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349

    APA Style (7th edition)

  • Bhatt, Sandeep. SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE. 2006. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349.

    MLA Style (8th edition)

  • Bhatt, Sandeep. "SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE." Doctoral dissertation, Kent State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349

    Chicago Manual of Style (17th edition)

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© 2006, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.