ArticleJournal of neuroinflammation2015
Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via PLCγ, PKC, and PI3K/Akt pathways during colitis.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review.Current neuropharmacology · 2019Pooled it
- Dorsal horn DCC amplification loop induced by endplate osteoclasts generates chronic nociplastic low back pain in male mice.Nature communications · 2026Article
- Multisystemic Consequences of Brain-Derived Neurotrophic Factor (BDNF) Haploinsufficiency in the SD-BDNFtm1sage Rat Model.International journal of molecular sciences · 2026Review
- The effects of physical exercise on inflammation-induced maladaptive neuroplasticity in post-traumatic headache.Neuroscience · 2026Review
- GABADrug design, development and therapy · 2026Review
- Neuroimmune regulation of visceral pain: roles of microglia, purinergic signaling, and neuroinflammation.Frontiers in immunology · 2026Review
- Neuroplasticity in Post-Traumatic Stress Disorder.Revista de neurologia · 2025Review
- Review
- Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception.International journal of molecular sciences · 2023Review
- AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models.Translational psychiatry · 2023Article
- Spinal cord astrocyte P2X7Rs mediate the inhibitory effect of electroacupuncture on visceral hypersensitivity of rat with irritable bowel syndrome.Purinergic signalling · 2023Article
- BDNF Therapeutic Mechanisms in Neuropsychiatric Disorders.International journal of molecular sciences · 2022Review
- Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The role of microglia in chronic pain and depression: innocent bystander or culprit?Psychopharmacology · 2021Review
- Electroacupuncture and Moxibustion Modulate the BDNF and TrkB Expression in the Colon and Dorsal Root Ganglia of IBS Rats with Visceral Hypersensitivity.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Article
- Spinal neuron-glia-immune interaction in cross-organ sensitization.American journal of physiology. Gastrointestinal and liver physiology · 2020Review
- Alternatively Polarized Macrophages Regulate the Growth and Differentiation of Ependymal Stem Cells through the SIRT2 Pathway.Experimental neurobiology · 2020Article
- BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis.Journal of neuroinflammation · 2020Article
- Electroacupuncture Inhibits the Activity of Astrocytes in Spinal Cord in Rats with Visceral Hypersensitivity by Inhibiting P2YEvidence-based complementary and alternative medicine : eCAM · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSpinal central sensitization is an important process in the generation and maintenance of visceral hypersensitivity. The release of brain-derived neurotrophic factor (BDNF) from the primary afferent neurons to the spinal cord contributes to spinal neuronal plasticity and increases neuronal activity and synaptic efficacy. The N-Methyl-D-aspartic acid (NMDA) receptor possesses ion channel properties, and its activity is modulated by phosphorylation of its subunits including the NMDA receptor 1 (NR1).
methodsColonic inflammation was induced by a single dose of intracolonic instillation of tri-nitrobenzene sulfonic acid (TNBS). NR1 phosphorylation by BDNF in vivo and in culture was examined by western blot and immunohistochemistry. Signal transduction was studied by direct examination and use of specific inhibitors.
resultsDuring colitis, the level of NR1 phospho-Ser(896) was increased in the dorsal horn region of the L1 and S1 spinal cord; this increase was attenuated by injection of BDNF neutralizing antibody to colitic animals (36 μg/kg, intravenous (i.v.)) and was also reduced in BDNF(+/-) rat treated with TNBS. Signal transduction examination showed that the extracellular signal-regulated kinase (ERK) activation was not involved in BDNF-induced NR1 phosphorylation. In contrast, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediated BDNF-induced NR1 phosphorylation in vivo and in culture; this is an additional pathway to the phospholipase C-gamma (PLCγ) and the protein kinase C (PKC) that was widely considered to phosphorylate NR1 at Ser(896). In spinal cord culture, the inhibitors to PLC (U73122), PKC (bisindolylmaleimide I), and PI3K (LY294002), but not MEK (PD98059) blocked BDNF-induced NR1 phosphorylation. In animals with colitis, treatment with LY294002 (50 μg/kg, i.v.) blocked the Akt activity as well as NR1 phosphorylation at Ser(896) in the spinal cord.
conclusionBDNF participates in colitis-induced spinal central sensitization by up-regulating NR1 phosphorylation at Ser(896). The PI3K/Akt pathway, in addition to PLCγ and PKC, mediates BDNF action in the spinal cord during colitis.
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