Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a standard treatment for Parkinson's disease (PD). However, in a considerable number of patients debilitating psychiatric side-effects occur. Recent research has revealed that external stimuli can alter the neurotransmitters' homeostasis in neurons, which is known as "neurotransmitter respecification". Herein, we addressed if neurotransmitter respecification could be a mechanism by which DBS suppresses the serotonergic function in the dorsal raphe nucleus (DRN) leading to mood changes. We infused transgenic 5-HT-Cre (ePET-Cre) mice with AAV viruses to achieve targeted expression of eYFP and the genetically encoded calcium indicator GCaMP6s in the DRN prior to methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Mice received bilateral DBS electrodes in the STN and an optic fiber in the DRN for calcium photometry. MPTP-treated mice demonstrated behavioral and histological PD phenotype, whereas all STN-DBS animals exhibited an increased immobility time in the forced swim test, reduced calcium activity, and loss of tryptophan hydroxylase-2 expression in the DRN. Given the prominent role of calcium transients in mediating neurotransmitter respecification, these results suggest a loss of serotonergic phenotype in the DRN following STN-DBS. These findings indicate that loss of serotonergic cell phenotype may underlie the unwanted depressive symptoms following STN-DBS.
Original language | English |
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Article number | 14011 |
Number of pages | 8 |
Journal | Scientific Reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 17 Aug 2022 |
Keywords
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism
- Animals
- Calcium/metabolism
- Deep Brain Stimulation/methods
- Mice
- Parkinson Disease/metabolism
- Phenotype
- Subthalamic Nucleus/physiology