ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Excitotoxicity downregulates TrkB.FL signaling and upregulates the neuroprotective truncated TrkB receptors in cultured hippocampal and striatal neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 93 citations in OpenAlex.
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- Synaptamide regulates astroglial functional activity after cerebral cortex injury.Inflammopharmacology · 2025Article
- Cleavage of the TrkB-FL receptor during epileptogenesis: insights from a kainic acid-induced model of epilepsy and human samples.Pharmacological research · 2025Article
- A brain-accessible peptide modulates stroke inflammatory response and neurotoxicity by targeting BDNF-receptor TrkB-T1 specific interactome.Theranostics · 2025Article
- A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Neurotrophins and Their Receptors: BDNF's Role in GABAergic Neurodevelopment and Disease.International journal of molecular sciences · 2024Review
- Oxidative Stress Plays an Important Role in Glutamatergic Excitotoxicity-Induced Cochlear Synaptopathy: Implication for Therapeutic Molecules Screening.Antioxidants (Basel, Switzerland) · 2024Article
- BDNF-TrkB/proBDNF-p75Scientific reports · 2023Article
- Chemogenetic inhibition of TrkB signalling reduces phrenic motor neuron survival and size.Molecular and cellular neurosciences · 2023Article
- SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice.Nature communications · 2022Article
- The effect of propofol on hypoxia- and TNF-α-mediated BDNF/TrkB pathway dysregulation in primary rat hippocampal neurons.CNS neuroscience & therapeutics · 2022Article
- Neuroinflammation as the Underlying Mechanism of Postoperative Cognitive Dysfunction and Therapeutic Strategies.Frontiers in cellular neuroscience · 2022Review
- High Caloric Diet Induces Memory Impairment and Disrupts Synaptic Plasticity in Aged Rats.Current issues in molecular biology · 2021Article
- Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential.International journal of molecular sciences · 2021Review
- Article
- N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.Advances in experimental medicine and biology · 2021Article
- Astrocytic BDNF and TrkB regulate severity and neuronal activity in mouse models of temporal lobe epilepsy.Cell death & disease · 2020Article
- Review
- Neuronal Activity and Its Role in Controlling Antioxidant Genes.International journal of molecular sciences · 2020Review
- Dysregulation of BDNF/TrkB signaling mediated by NMDAR/CaJournal of neuroinflammation · 2020Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival through activation of TrkB receptors. The trkB gene encodes a full-length receptor tyrosine kinase (TrkB.FL) and its truncated (T1/T2) isoforms. We investigated the changes in TrkB protein levels and signaling activity under excitotoxic conditions, which are characteristic of brain ischemia, traumatic brain injury, and neurodegenerative disorders. Excitotoxic stimulation of cultured rat hippocampal or striatal neurons downregulated TrkB.FL and upregulated a truncated form of the receptor (TrkB.T). Downregulation of TrkB.FL was mediated by calpains, whereas the increase in TrkB.T protein levels required transcription and translation activities. Downregulation of TrkB.FL receptors in hippocampal neurons correlated with a decrease in BDNF-induced activation of the Ras/ERK and PLCγ pathways. However, calpain inhibition, which prevents TrkB.FL degradation, did not preclude the decrease in signaling activity of these receptors. On the other hand, incubation with anisomycin, to prevent the upregulation of TrkB.T, protected to a large extent the TrkB.FL signaling activity, suggesting that truncated receptors may act as dominant-negatives. The upregulation of TrkB.T under excitotoxic conditions was correlated with an increase in BDNF-induced inhibition of RhoA, a mediator of excitotoxic neuronal death. BDNF fully protected hippocampal neurons transduced with TrkB.T when present during excitotoxic stimulation with glutamate, in contrast with the partial protection observed in cells overexpressing TrkB.FL or expressing GFP. These results indicate that BDNF protects hippocampal neurons by two distinct mechanisms: through the neurotrophic effects of TrkB.FL receptors and by activation of TrkB.T receptors coupled to inhibition of the excitotoxic signaling.
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