ArticleeNeuro2023
The Neurotoxin DSP-4 Dysregulates the Locus Coeruleus-Norepinephrine System and Recapitulates Molecular and Behavioral Aspects of Prodromal Neurodegenerative Disease.
Article in eNeuro, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- A new hope: locus coeruleus-norepinephrine system at the nexus of neuropsychiatric symptoms.Molecular psychiatry · 2026Review
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.Molecular psychiatry · 2026Article
- The locus coeruleus at the crossroads of inflammation and neurodegeneration in multiple sclerosis.Journal of neuroinflammation · 2026Review
- Astrocyte reactivity modifies the effects of locus coeruleus norepinephrine-related dysfunction on tau and its impact on cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility.Methods (San Diego, Calif.) · 2026Article
- Locus coeruleus α-synuclein overexpression induces prodromal Parkinsonian features in mice.NPJ Parkinson's disease · 2026Article
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Photostimulation of locus coeruleus CA1 catecholaminergic terminals reversed Spatial memory impairment in an alzheimer's disease mouse model.Psychopharmacology · 2026Article
- The role of the locus coeruleus in giant migrating contractions of colonic motility in Suncus murinus.Experimental brain research · 2026Article
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Neurodegeneration in Parkinson's Disease: The Role of Environmental Toxins.Journal of central nervous system disease · 2026Review
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.bioRxiv : the preprint server for biology · 2025Article
- Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system.Pharmacological reviews · 2025Review
- Regenerating Locus Coeruleus-Norepinephrine (LC-NE) Function: A Novel Approach for Neurodegenerative Diseases.Cell proliferation · 2025Review
- Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus.bioRxiv : the preprint server for biology · 2025Article
- Pharmacologically increasing O-GlcNAcylation increases complexity of astrocytes in the dentate gyrus of TgF344-AD rats.Frontiers in aging neuroscience · 2025Article
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- Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.bioRxiv : the preprint server for biology · 2024Article
- Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer's disease.Alzheimer's research & therapy · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify the links between pathology and dysfunction. We employed the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which preferentially damages LC axons, to model early changes in the LC-NE system pertinent to AD and PD in male and female mice. DSP-4 (two doses of 50 mg/kg, one week apart) induced LC axon degeneration, triggered neuroinflammation and oxidative stress, and reduced tissue NE levels. There was no LC cell death or changes to LC firing, but transcriptomics revealed reduced expression of genes that define noradrenergic identity and other changes relevant to neurodegenerative disease. Despite the dramatic loss of LC fibers, NE turnover and signaling were elevated in terminal regions and were associated with anxiogenic phenotypes in multiple behavioral tests. These results represent a comprehensive analysis of how the LC-NE system responds to axon/terminal damage reminiscent of early AD and PD at the molecular, cellular, systems, and behavioral levels, and provides potential mechanisms underlying prodromal neuropsychiatric symptoms.
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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.