Stemick, Judith and Gauer, Carina and Wihan, Jeanette and Moceri, Sandra and Xiang, Wei and von Hoersten, Stephan and Kohl, Zacharias and Winkler, Juergen (2020) Compensatory neuritogenesis of serotonergic afferents within the striatum of a transgenic rat model of Parkinson's disease. BRAIN RESEARCH, 1748: 147119. ISSN 0006-8993, 1872-6240
Full text not available from this repository. (Request a copy)Abstract
The majority of patients with Parkinson's disease (PD) suffer from L-DOPA-induced dyskinesia (LID). Besides a dysfunctional dopaminergic system, changes of the serotonergic network may be linked to this severe and adverse symptom. Particularly, serotonergic neurons have the potential to synthesize dopamine, likely associated with a disproportional dopamine release within the striatum. We hypothesized that the serotonergic system is adaptively altered in the striatum due to the reduced dopaminergic input. To answer this question, we analyzed a transgenic rat PD model ubiquitously expressing human alpha-synuclein using a bacterial artificial chromosome. Neurite analysis showed a profound loss of dopaminergic fibers by similar to 30-40% within the dorsal striatum paralleled by a similar to 50% reduction of dopaminergic neurons in the substantia nigra pars compacta. In contrast, serotonergic fibers showed an increased fiber density in the dorsal striatum by similar to 100%, while the number of serotonergic neurons within the raphe nuclei (RN) and its proximal neuritic processes were unaffected. Furthermore, both the dopaminergic and serotonergic fiber density remained unchanged in the neighboring motor cortex M1/M2. Interestingly, essential enzymes required for L-DOPA turnover and dopamine release were expressed in serotonergic neurons of the RN. In parallel, the serotonergic autoreceptor levels involved in a serotonergic negative feedback loop were reduced within the striatum, suggesting a dysfunctional neurotransmitter release. Overall, the increased serotonergic fiber density with its capacity for dopamine release within the striatum suggests a compensatory, site-specific serotonergic neuritogenesis. This maladaptive serotonergic plasticity may be linked to adverse symptoms such as LIDs in PD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOPA-INDUCED DYSKINESIA; EXOGENOUS L-DOPA; DOPAMINERGIC SYSTEM; ALPHA-SYNUCLEIN; EXPRESSION; NEURONS; TRANSPORTER; HYPERINNERVATION; TERMINALS; DORSAL; Parkinson's disease; alpha-synuclein; Dopamine; Serotonin; Striatum; L-DOPA-induced dyskinesia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 08:04 |
| Last Modified: | 08 Mar 2021 08:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43316 |
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