Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse
Abstract Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson’s disease (PD). The progression of the disease and inherent disruption of the DA neurotransmission has bee...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49600-5 |
| _version_ | 1827388468905377792 |
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| author | Jose Medina-Luque Patrick Piechocinski Paul Feyen Carmelo Sgobio Jochen Herms |
| author_facet | Jose Medina-Luque Patrick Piechocinski Paul Feyen Carmelo Sgobio Jochen Herms |
| author_sort | Jose Medina-Luque |
| collection | DOAJ |
| description | Abstract Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson’s disease (PD). The progression of the disease and inherent disruption of the DA neurotransmission has been closely related to accumulation of the synaptic protein α-synuclein. However, it is still unclear how α-synuclein affects dopaminergic terminals in different areas of dorsal striatum. Here we demonstrate that the overexpression of human α-synuclein (h-α-syn) interferes with the striatal DA neurotransmission in an age‐dependent manner, preferentially in the dorsolateral striatum (DLS) of PDGF-h-α-syn mice. While 3-month-old mice showed an increase at the onset of h-α-syn accumulation in the DLS, 12-month-old mice revealed a decrease in electrically-evoked DA release. The enhanced DA release in 3-month-old mice coincided with better performance in a behavioural task. Notably, DA amplitude alterations were also accompanied by a delay in the DA clearance independently from the animal age. Structurally, dopamine transporter (DAT) was found to be redistributed in larger DAT-positive clumps only in the DLS of 3- and 12-month-old mice. Together, our data provide new insight into the vulnerability of DLS and suggest DAT-related dysfunctionalities from the very early stages of h-α-syn accumulation. |
| first_indexed | 2024-03-08T16:20:20Z |
| format | Article |
| id | doaj.art-4d7541a07b904ff29cc1ee42cd0555f5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:20:20Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4d7541a07b904ff29cc1ee42cd0555f52024-01-07T12:24:56ZengNature PortfolioScientific Reports2045-23222024-01-0114111110.1038/s41598-023-49600-5Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouseJose Medina-Luque0Patrick Piechocinski1Paul Feyen2Carmelo Sgobio3Jochen Herms4German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)Abstract Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson’s disease (PD). The progression of the disease and inherent disruption of the DA neurotransmission has been closely related to accumulation of the synaptic protein α-synuclein. However, it is still unclear how α-synuclein affects dopaminergic terminals in different areas of dorsal striatum. Here we demonstrate that the overexpression of human α-synuclein (h-α-syn) interferes with the striatal DA neurotransmission in an age‐dependent manner, preferentially in the dorsolateral striatum (DLS) of PDGF-h-α-syn mice. While 3-month-old mice showed an increase at the onset of h-α-syn accumulation in the DLS, 12-month-old mice revealed a decrease in electrically-evoked DA release. The enhanced DA release in 3-month-old mice coincided with better performance in a behavioural task. Notably, DA amplitude alterations were also accompanied by a delay in the DA clearance independently from the animal age. Structurally, dopamine transporter (DAT) was found to be redistributed in larger DAT-positive clumps only in the DLS of 3- and 12-month-old mice. Together, our data provide new insight into the vulnerability of DLS and suggest DAT-related dysfunctionalities from the very early stages of h-α-syn accumulation.https://doi.org/10.1038/s41598-023-49600-5 |
| spellingShingle | Jose Medina-Luque Patrick Piechocinski Paul Feyen Carmelo Sgobio Jochen Herms Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse Scientific Reports |
| title | Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse |
| title_full | Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse |
| title_fullStr | Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse |
| title_full_unstemmed | Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse |
| title_short | Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson’s disease transgenic mouse |
| title_sort | striatal dopamine neurotransmission is altered in age and region specific manner in a parkinson s disease transgenic mouse |
| url | https://doi.org/10.1038/s41598-023-49600-5 |
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