ArticleProceedings of the National Academy of Sciences of the United States of America2013
Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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
103 citing papers in PubMed, 173 citations in OpenAlex.
- Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial.Neurology · 2014Trial
- The Role of Serotonergic System in Parkinson's Disease-Related Pain.Neuroscience bulletin · 2026Review
- Acute DOI exposure drives cortical hyperexcitability and functional network remodeling.bioRxiv : the preprint server for biology · 2026Article
- Modeling cerebral palsy in animals.Developmental medicine and child neurology · 2026Review
- KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.Frontiers in molecular neuroscience · 2026Article
- Motion-Style Scalp Acupuncture Ameliorates Post-Stroke Muscle Spasticity Through Cerebral Blood Flow Augmentation and 5-HTBrain and behavior · 2025Article
- KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury.The Journal of physiology · 2025Article
- Transcutaneous Spinal Stimulation Modulates Spinal Reflex Circuit Excitability in Persons with Spinal Cord Injury.Biomedicines · 2025Article
- Spinal Calcrl+ neurons amplify mechanical itch signaling via synaptic plasticity in chronic itch model.PloS one · 2025Article
- Dorsoventral photobiomodulation therapy safely reduces inflammation and sensorimotor deficits in a mouse model of multiple sclerosis.Journal of neuroinflammation · 2024Article
- Mirtazapine Improves Locomotor Activity and Attenuates Neuropathic Pain Following Spinal Cord Injury in Rats via Neuroinflammation Modulation.Neurochemical research · 2024Article
- VEGF, but Not BDNF, Prevents the Downregulation of KCC2 Induced by Axotomy in Extraocular Motoneurons.International journal of molecular sciences · 2024Article
- Oxytocin Exhibits Neuroprotective Effects on Hippocampal Cultures under Severe Oxygen-Glucose Deprivation Conditions.Current issues in molecular biology · 2024Article
- Noise-induced hearing loss alters potassium-chloride cotransporter KCC2 and GABA inhibition in the auditory centers.Scientific reports · 2024Article
- Knockdown of calpain1 in lumbar motoneurons reduces spasticity after spinal cord injury in adult rats.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Serotonergic dysfunction impairs locomotor coordination in spinal muscular atrophy.Brain : a journal of neurology · 2023Article
- Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers.Research square · 2023Article
- Preservation of KCC2 expression in axotomized abducens motoneurons and its enhancement by VEGF.Brain structure & function · 2023Article
- Bumetanide increases postsynaptic inhibition after chronic SCI and decreases presynaptic inhibition with step-training.The Journal of physiology · 2023Article
- Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain.Cells · 2022Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In healthy adults, activation of γ-aminobutyric acid (GABA)(A) and glycine receptors inhibits neurons as a result of low intracellular chloride concentration ([Cl(-)](i)), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, including spasticity and chronic pain following spinal cord injury (SCI). Given the critical role of KCC2 in regulating the strength and robustness of inhibition, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance. We show that activation of 5-hydroxytryptamine (5-HT) type 2A receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials (IPSPs), E(IPSP), in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after SCI in rats. Up-regulation of KCC2 function by targeting 5-HT(2A) receptors, therefore, has therapeutic potential in the treatment of neurological disorders involving altered chloride homeostasis. However, these receptors have been implicated in several psychiatric disorders, and their effects on pain processing are controversial, highlighting the need to further investigate the potential systemic effects of specific 5-HT(2A)R agonists, such as (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).
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.