Evidence map›Paper›PMID 39561852›Full record

ArticleNeuropharmacology2025

Effects of genetic knockdown of the serotonin transporter on established L-DOPA-induced dyskinesia and gene expression in hemiparkinsonian rats.

Grace McManus, Ashley Galfano, Carla Budrow, Natalie Lipari, Kuei Y Tseng, Fredric P Manfredsson, Christopher Bishop

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Grace McManusBehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY, 13902, USA. Electronic address: gmcmanu4@binghamton.edu.
Ashley GalfanoBehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY, 13902, USA.
Carla BudrowBehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY, 13902, USA.
Natalie LipariBehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY, 13902, USA.
Kuei Y TsengDepartment of Anatomy and Cell Biology, University of Illinois Chicago - College of Medicine, Chicago, IL, 60612, USA.
Fredric P ManfredssonDepartment of Translational Neuroscience, Barrow Neurological Institute, Pheonix, AZ, 85013, USA.
Christopher BishopBehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY, 13902, USA. Electronic address: cbishop@binghamton.edu.

Funding

Interrogating Maladaptive Serotonin Raphe-Striatal Plasticity in L-DOPA-Induced DyskinesiaR01NS122226 · NINDS · STATE UNIVERSITY OF NY,BINGHAMTON · PI CHRISTOPHER R BISHOP, Fredric Manfredsson · 2022 to 2026
$3.1M
NINDS NIH HHS R01 NS122226
6 · The paper itself

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder typified by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) leading to motor symptoms including resting tremor, rigidity, akinesia, and postural instability. DA replacement therapy with levodopa (L-DOPA) remains the gold-standard treatment for the motor symptoms of PD. Unfortunately, chronic use of L-DOPA leads to the development of side effects known as L-DOPA-induced dyskinesia (LID). The mechanisms underlying LID are multifaceted, but accumulating research has strongly implicated maladaptive neuroplasticity within the raphe-striatal serotonin (5-HT) circuit. The 5-HT transporter (SERT) has emerged as an intriguing therapeutic target as it is upregulated in the brains of dyskinetic patients and animal models of LID, and pharmacological blockade of SERT alters L-DOPA's effects. Therefore, the current study employed an interventional genetic knockdown of SERT (SERT-KD) to investigate its role in LID expression and LID-associated transcription factors. To do so, hemiparkinsonian, stably dyskinetic rats (N = 68) received adeno-associated virus 9 (AAV9) expressing either a short-hairpin RNA against SERT (SERT-shRNA) or a scrambled control shRNA (SCR-shRNA) after which LID reinstatement and motor performance were assayed over 2 weeks. Dorsal raphe and striatal tissue were collected for the expression analyses of known parkinsonian and LID-associated genes. Results demonstrated that SERT-KD significantly and durably reduced LID and L-DOPA-induced striatal cFOS mRNA without altering L-DOPA efficacy. Such findings point to SERT-mediated adaptations as a 5-HT mechanism by which L-DOPA exerts its actions and therapeutic target for LID.

Indexed as

Antiparkinson AgentsDyskinesia, Drug-InducedLevodopaParkinsonian DisordersSerotonin Plasma Membrane Transport ProteinsAnimalsCorpus StriatumDisease Models, AnimalGene ExpressionGene Knockdown TechniquesMaleOxidopamineProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleyAntiparkinson AgentsLevodopaOxidopamineProto-Oncogene Proteins c-fosSerotonin Plasma Membrane Transport ProteinsDopamineDorsal raphe nucleusLevodopa-induced dyskinesiaParkinson's diseaseSerotonin transporterShort-hairpin RNAStriatum

Identifiers

PMID39561852
PMCPMC12641275

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.