ArticlePloS one2022
Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Pathogenesis and treatment of perioperative hiccups: a narrative review.Annals of medicine · 2025Pooled it
- Neuroinflammation and noradrenergic modulation with β2-adrenoceptors: Emerging therapeutic targets for Parkinson's diseases.Neural regeneration research · 2026Article
- Locus coeruleus α-synuclein overexpression induces prodromal Parkinsonian features in mice.NPJ Parkinson's disease · 2026Article
- Rise-and-fall dynamics reveal a molecular and cellular vulnerability axis in prion-likebioRxiv : the preprint server for biology · 2026Article
- Neural Circuit Connections and Functions of Locus Coeruleus-Norepinephrine System.International journal of molecular sciences · 2025Review
- Lower prevalence of metabolic syndrome and its components in the prediagnostic phase of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Regenerating Locus Coeruleus-Norepinephrine (LC-NE) Function: A Novel Approach for Neurodegenerative Diseases.Cell proliferation · 2025Review
- Progressive noradrenergic degeneration and motor cortical dysfunction in Parkinson's disease.Acta pharmacologica Sinica · 2025Review
- Pathogenesis of depression and the potential for traditional Chinese medicine treatment.Frontiers in pharmacology · 2024Review
- A review of the pharmacological action and mechanism of natural plant polysaccharides in depression.Frontiers in pharmacology · 2024Review
- The noradrenergic subtype of Parkinson disease: from animal models to clinical practice.Nature reviews. Neurology · 2023Review
- Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study.Biomedicines · 2022Review
- Differential vulnerability of locus coeruleus and dorsal raphe neurons to chronic methamphetamine-induced degeneration.Frontiers in cellular neuroscience · 2022Article
- Locus coeruleus alterations in dementia with Lewy bodies: A systematic review.Alzheimer's & dementia (New York, N. Y.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dopaminergic neuron degeneration in the midbrain plays a pivotal role in motor symptoms associated with Parkinson's disease. However, non-motor symptoms of Parkinson's disease and post-mortem histopathology confirm dysfunction in other brain areas, including the locus coeruleus and its associated neurotransmitter norepinephrine. Here, we investigate the role of central norepinephrine-producing neurons in Parkinson's disease by chronically stimulating catecholaminergic neurons in the locus coeruleus using chemogenetic manipulation. We show that norepinephrine neurons send complex axonal projections to the dopaminergic neurons in the substantia nigra, confirming physical communication between these regions. Furthermore, we demonstrate that increased activity of norepinephrine neurons is protective against dopaminergic neuronal depletion in human α-syn A53T missense mutation over-expressing mice and prevents motor dysfunction in these mice. Remarkably, elevated norepinephrine neurons action fails to alleviate α-synuclein aggregation and microgliosis in the substantia nigra suggesting the presence of an alternate neuroprotective mechanism. The beneficial effects of high norepinephrine neuron activity might be attributed to the action of norepinephrine on dopaminergic neurons, as recombinant norepinephrine treatment increased primary dopaminergic neuron cultures survival and neurite sprouting. Collectively, our results suggest a neuroprotective mechanism where noradrenergic neurons activity preserves the integrity of dopaminergic neurons, which prevents synucleinopathy-dependent loss of these cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.