ArticlePharmaceutical biology2022
Paclitaxel induces cognitive impairment via necroptosis, decreased synaptic plasticity and M1 polarisation of microglia.
Article in Pharmaceutical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Astrocytic NLRP3 cKO Mitigates Cognitive Impairment Induced by Paclitaxel in Mice.Neurochemical research · 2026Article
- Cancer therapy-related cognitive impairment, part 1: an integrative clinical-mechanistic framework from phenotypes to convergent neurobiological pathways.Pharmacological reports : PR · 2026Review
- Effects of Kongsheng Zhenzhong Pills on Neuroinflammation and cGAS-STING Pathway Activity in BV-2 Microglia.Biomedicines · 2026Article
- Cognitive Impairment Associated with Chemotherapy: Neuroimmunological Interactions, Gut-Brain Axis, and Therapeutic Approaches.Brain sciences · 2026Review
- Mechanistic insights into taxane-induced psychiatric adverse events: a global pharmacovigilance and experimental investigation.Molecular psychiatry · 2026Article
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Changes in gut, microbiome, and cognition after doxorubicin, cyclophosphamide, and paclitaxel chemotherapy treatment.Scientific reports · 2026Article
- Paclitaxel-induced adverse effects: insights into multi-organ toxicities and molecular mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Trajectories and related factors of subjective cognitive function in patients living with breast cancer receiving postoperative chemotherapy: a latent class growth model study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- MCC950 Reduces the Anxiodepressive-like Behaviors and Memory Deficits Related to Paclitaxel-Induced Peripheral Neuropathy in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway.Open medicine (Warsaw, Poland) · 2025Article
- Paclitaxel-induced cognitive impairment: mechanistic insights.Frontiers in pharmacology · 2025Review
- Effects of preoperative neoadjuvant chemotherapy on postoperative delirium in patients with gynecological tumor surgery: an observational study.Journal of cancer research and clinical oncology · 2024Observational
- Nanotechnology Approaches for Prevention and Treatment of Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors.Small (Weinheim an der Bergstrasse, Germany) · 2024Review
- Crosstalk of non-apoptotic RCD panel in hepatocellular carcinoma reveals the prognostic and therapeutic optimization.iScience · 2024Article
- Immune drivers of physiological and pathological pain.The Journal of experimental medicine · 2024Article
- Potential of Natural Phenolic Compounds against Doxorubicin-Induced Chemobrain: Biological and Molecular Mechanisms Involved.Antioxidants (Basel, Switzerland) · 2024Review
- Taming microglia: the promise of engineered microglia in treating neurological diseases.Journal of neuroinflammation · 2024Review
- Chemotherapy-Mediated Neuronal Aberration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction.Frontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextPaclitaxel (PTX) leads to chemotherapy brain (chemo-brain) which is characterised by cognitive impairment. It has been reported that necroptosis is associated with cognitive impairment in some neurodegenerative diseases, but it is not clear whether it is related to the development of chemo-brain.
objectiveTo investigate the role of necroptosis and related changes in PTX-induced cognitive impairment. MATERIALS AND
methodsC57bl/6n mice were randomly divided into five groups: control, vehicle, and different concentrations of PTX (6, 8, 10 mg/kg). Two additional groups received pre-treatment with Gdcl3 or PBS through Intracerebroventricular (ICV) injection before PTX-treatment. Cognitive function, necroptosis, synaptic plasticity and microglia polarisation were analysed.
resultsPTX (10 mg/kg) induced significant cognitive impairment, accompanied by changes in synaptic plasticity, including decreased density of PSD95 (0.65-fold), BDNF (0.44-fold) and dendritic spines (0.57-fold). PTX induced necroptosis of 53.41% (RIP3) and 61.91% (MLKL) in hippocampal neurons, with high expression of RIP3 (1.58-fold) compared with the control group. MLKL (1.87-fold) exhibited the same trend, reaching a peak on the 14th day. The increased expression of iNOS (1.63-fold) and inflammatory factors such as TNF-α (1.85-fold) and IL-β (1.89-fold) compared to the control group suggests that M1 polarisation of microglia is involved in the process of cognitive impairment. Pre-treatment with Gdcl3 effectively reduced the number of microglia (0.50-fold), inhibited the release of TNF-α (0.73-fold) and IL-β (0.56-fold), and improved cognitive impairment.
conclusionWe established a stable animal model of PTX-induced cognitive impairment and explored the underlying pathophysiological mechanism. These findings can guide the future treatment of chemo-brain.
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