Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys
The subthalamic nucleus (STN), the main driving force of the basal ganglia, is innervated by brainstem serotonin (5-HT) neurons with highly plastic axonal arborization. A pathologically-induced rearrangement of the ascending 5-HT projections could contribute to the disrupted firing pattern of STN ne...
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Elsevier
2025-07-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125001548 |
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| author | C.V.L. Delmas J. Munro M. Bérard T. Di Paolo M. Morissette M.E. Tremblay A. Parent M. Parent |
| author_facet | C.V.L. Delmas J. Munro M. Bérard T. Di Paolo M. Morissette M.E. Tremblay A. Parent M. Parent |
| author_sort | C.V.L. Delmas |
| collection | DOAJ |
| description | The subthalamic nucleus (STN), the main driving force of the basal ganglia, is innervated by brainstem serotonin (5-HT) neurons with highly plastic axonal arborization. A pathologically-induced rearrangement of the ascending 5-HT projections could contribute to the disrupted firing pattern of STN neurons observed in Parkinson's disease (PD). This light and electron microscope study was designed to characterize the neuroadaptive changes of 5-HT inputs to the different functional territories of the STN in four cynomolgus monkeys (Macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and four control animals. Using an unbiased stereological approach, we report a significant decrease of the density of 5-HT axon varicosities immunolabeled for the 5-HT membrane transporter (SERT), across all STN functional territories of MPTP-treated monkeys. In MPTP-treated animals, the SERT+ axon varicosities are larger than in control monkeys. In both experimental conditions they are only partially synaptic. A preserved length of 5-HT axons in the STN along with a conserved number of 5-HT neurons in the dorsal raphe nucleus is observed. Overall, our results indicate that, in parkinsonian monkeys, the 5-HT axons projecting to the STN are preserved but endowed with significantly less axon varicosities. Such neuroadaptive change could lead to a lower ambient level of 5-HT in this basal ganglia component, representing a compensatory mechanism designed to cope with the hyperexcitability of STN neurons that is known to occur in PD. |
| format | Article |
| id | doaj-art-e7ccf442bd9246ffbe837136db0a89ac |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-e7ccf442bd9246ffbe837136db0a89ac2025-08-20T03:49:03ZengElsevierNeurobiology of Disease1095-953X2025-07-0121110693810.1016/j.nbd.2025.106938Serotonin innervation of the subthalamic nucleus in parkinsonian monkeysC.V.L. Delmas0J. Munro1M. Bérard2T. Di Paolo3M. Morissette4M.E. Tremblay5A. Parent6M. Parent7CERVO Brain Research Center and Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, CanadaCERVO Brain Research Center and Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, CanadaCERVO Brain Research Center and Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, CanadaCentre de recherche du CHU de Québec and Faculty of Pharmacy, Université Laval, Quebec City, QC G1V 4G2, CanadaCentre de recherche du CHU de Québec and Faculty of Pharmacy, Université Laval, Quebec City, QC G1V 4G2, CanadaUniversity of Victoria, Division of Medical Sciences, Victoria, BC V8P 5C2, CanadaCERVO Brain Research Center and Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, CanadaCERVO Brain Research Center and Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada; Corresponding author at: CERVO Brain Research Centre, 2601, Canardière, Room F-6530-1, Quebec City (Quebec) G1J 2G3, Canada.The subthalamic nucleus (STN), the main driving force of the basal ganglia, is innervated by brainstem serotonin (5-HT) neurons with highly plastic axonal arborization. A pathologically-induced rearrangement of the ascending 5-HT projections could contribute to the disrupted firing pattern of STN neurons observed in Parkinson's disease (PD). This light and electron microscope study was designed to characterize the neuroadaptive changes of 5-HT inputs to the different functional territories of the STN in four cynomolgus monkeys (Macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and four control animals. Using an unbiased stereological approach, we report a significant decrease of the density of 5-HT axon varicosities immunolabeled for the 5-HT membrane transporter (SERT), across all STN functional territories of MPTP-treated monkeys. In MPTP-treated animals, the SERT+ axon varicosities are larger than in control monkeys. In both experimental conditions they are only partially synaptic. A preserved length of 5-HT axons in the STN along with a conserved number of 5-HT neurons in the dorsal raphe nucleus is observed. Overall, our results indicate that, in parkinsonian monkeys, the 5-HT axons projecting to the STN are preserved but endowed with significantly less axon varicosities. Such neuroadaptive change could lead to a lower ambient level of 5-HT in this basal ganglia component, representing a compensatory mechanism designed to cope with the hyperexcitability of STN neurons that is known to occur in PD.http://www.sciencedirect.com/science/article/pii/S0969996125001548Basal gangliaParkinson's diseaseNon-human primatesMPTP-intoxicated monkeysStereologyElectron microscopy |
| spellingShingle | C.V.L. Delmas J. Munro M. Bérard T. Di Paolo M. Morissette M.E. Tremblay A. Parent M. Parent Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys Neurobiology of Disease Basal ganglia Parkinson's disease Non-human primates MPTP-intoxicated monkeys Stereology Electron microscopy |
| title | Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys |
| title_full | Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys |
| title_fullStr | Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys |
| title_full_unstemmed | Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys |
| title_short | Serotonin innervation of the subthalamic nucleus in parkinsonian monkeys |
| title_sort | serotonin innervation of the subthalamic nucleus in parkinsonian monkeys |
| topic | Basal ganglia Parkinson's disease Non-human primates MPTP-intoxicated monkeys Stereology Electron microscopy |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125001548 |
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