SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE
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Kent State University / OhioLINK
2006
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-kent11641413492021-08-03T05:36:13Z SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE Bhatt, Sandeep Parkinson's Disease Dopamine Transporter Vesicular Monoamine Transporter 2 Neurodegeneration 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. 2006-11-28 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349 http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Parkinson's Disease Dopamine Transporter Vesicular Monoamine Transporter 2 Neurodegeneration |
| spellingShingle |
Parkinson's Disease Dopamine Transporter Vesicular Monoamine Transporter 2 Neurodegeneration Bhatt, Sandeep SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE |
| author |
Bhatt, Sandeep |
| author_facet |
Bhatt, Sandeep |
| author_sort |
Bhatt, Sandeep |
| title |
SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE |
| title_short |
SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE |
| title_full |
SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE |
| title_fullStr |
SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE |
| title_full_unstemmed |
SEX DIFFERENCES IN DOPAMINE REUPTAKE PATHWAYS OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MICE |
| title_sort |
sex differences in dopamine reuptake pathways of the nigrostriatal dopaminergic system in mice |
| publisher |
Kent State University / OhioLINK |
| publishDate |
2006 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=kent1164141349 |
| work_keys_str_mv |
AT bhattsandeep sexdifferencesindopaminereuptakepathwaysofthenigrostriataldopaminergicsysteminmice |
| _version_ |
1719422369680850944 |