Neurotoxic effects of nanoplastics exposure on depression-like behavior and cognitive function in mice under chronic unpredictable mild stress.
Efectos neurotóxicos de la exposición a nanoplásticos sobre el comportamiento similar a la depresión y la función cognitiva en ratones sometidos a estrés crónico leve impredecible.
Palabras clave:
Nanoplásticos, Microplásticos, Nanopartículas, BDNF/TrkB, Estrés Crónico, Comportamiento similar a la depresión, Hipocampo
Resumen
En el presente estudio se evaluó el impacto de la exposición a nanoplásticos sobre el deterioro cognitivo y el comportamiento depresivo en ratones sometidos a estrés moderado crónico e impredecible (CUMS). Ratones BALB/c fueron asignados aleatoriamente a cuatro grupos experimentales: Control (Ctrl), nanoplásticos (NPs), Mod (sometidos a CUMS) y NPs+Mod (nanoplásticos + CUMS). Se determinó el papel del factor de crecimiento derivado del cerebro (BDNF) y su vía de señalización a través del receptor de la tirosina quinasa B (TrkB) en el hipocampo. Las pruebas de comportamiento incluyeron la prueba de preferencia por la sacarosa, la actividad motora en campo abierto, el nado forzado y el laberinto de Morris. Se evaluaron la morfología neuronal y la expresión de BDNF y TrkB mediante técnicas de PCR cuantitativa y Western blot. La exposición a los nanoplásticos, así como el estrés crónico, indujeron una disminución de la actividad en las pruebas de conducta. Además, se observó una disminución de las neuronas del hipocampo y de la memoria espacial en ambos tratamientos. La combinación de estrés crónico y la exposición a los nanoplásticos tuvo un efecto sumativo sobre las pruebas conductuales y cognitivas, así como sobre la expresión de BDNF y del receptor Trak B. En conclusión, la exposición a los nano-plásticos tiene efectos neurotóxicos que pueden potenciar los efectos del estrés crónico a nivel cognitivo y conductual. Dichos efectos se mediaron mediante la supresión de la vía de señalización de BDNF y del receptor TrkB en el hipocampo.
Descargas
La descarga de datos todavía no está disponible.
Citas
Liu Q, Hu W, Zhang Y, Ning J, Pang Y, Hu H, et al. Comprehensive analysis of lncRNA-mRNA expression profiles in depression-like responses of mice related to Polystyrene Nanoparticle exposure. Toxics. 2023;11(7):600. https://doi.org/10.3390/toxics11070600.
Li F, Xiang H, Gu Y, Ye T, Lu X, Huang C. Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice. J Neuroinflammation. 2022;19(1):12. https://doi.org/10.1186/12974-021-02377-8.
Simon GE, Moise N, Mohr DC. Management of Depression in Adults: A Review. JAMA. 2024;332(2):141-152. https://doi.org/10.1001/jama.2024.5756.
Jha MK, Mathew SJ. Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape. Am J Psychiatry. 2023;180(3):190-199. https://doi.org/10.1176/appi.ajp.20230025.
Sun Y, Hu N, Wang M, Lu L, Luo C, Tang B, et al. Hippocampal subfield alterations in schizophrenia and major depressive disorder: a systematic review and network meta-analysis of anatomic MRI studies. J Psychiatry Neurosci. 2023;48(1): E34-e49. https://doi.org/10.1503/jpn.220086.
Althammer F, Roy RK, Kirchner MK, Campos-Lira E, Whitley KE, Davis S, et al. Angiotensin II-Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats. Hypertension. 2023;80(6):1258-1273.https://doi.org/10.1161/HYPERTENSIONAHA.123.21070.
Nieto-Estévez V, Defterali Ç, Vicario C. Distinct Effects of BDNF and NT-3 on the Dendrites and Presynaptic Boutons of Developing Olfactory Bulb GABAergic Interneurons in Vitro. Cell Mol Neurobiol. 2022;42(5):1399-1417. https://doi.org/10.1007/s10571-020-01030-x. PMC11421695.
Sharma S, Chawla S, Kumar P, Ahmad R, Kumar Verma P. The chronic unpredictable mild stress (CUMS) Paradigm: Bridging the gap in depression research from bench to bedside. Brain Res. 2024;1843:149123. https://doi.org/10.1016/j.brainres.2024.149123.
Deng Y, Chen H, Huang Y, Zhang Y, Ren H, Fang M, et al. Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference. Environ Sci Technol. 2022;56(22):15805-15817. https://doi.org/10.1021/acs.est.1e07933.
Antoniuk S, Bijata M, Ponimaskin E, Włodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev. 2019;99: 101-116. https://doi.org/10.1016/j.neubiorev.2018.12.002.
Xie J, Ji J, Sun Y, Ma Y, Wu D, Zhang Z. Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system. J Hazard Mater. 2024;480: 136028. https://doi.org/10.1016/j.jhazmat.2024.136028.
Khataminezhad ES, Hajihassan Z, Razi Astaraei F. Magnetically purification/immobilization of polyhistidine-tagged proteins by PEGylated magnetic graphene oxide nanocomposites. Protein Expres Purif. 2023;207: 106264. https://doi.org/10.1016/j.pep.2023.106264.
Yang J, Li H, Hao Z, Jing X, Zhao Y, Cheng X, et al. Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway. ACS Appl Mater Interfaces. 2022;14(3):3685-3700. https://doi.org/10.1021/acsami.1c18417.
Shorey S, Ng ED, Wong CHJ. Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis. Br J Clin Psychol. 2022;61(2):287-305. https://doi.org/10.1111/bjc.12333.
Su Z, Kong R, Huang C, Wang K, Liu C, Gu X, et al. Exposure to polystyrene nanoplastics causes anxiety and depressive-like behavior and down-regulates EAAT2 expression in mice. Arch Toxicol. 2025;99(6):2595-2609. https://doi.org/10.1007/s00204-025-04002-6.
Wu C, Jia L, Mu Q, Fang Z, Hamoudi H, Huang M, et al. Altered hippocampal subfield volumes in major depressive disorder with and without anhedonia. BMC Psychiatry. 2023;23(1):540. https://doi.org/10.1186/s12888-023-05001-6.
Diersch N, Valdes-Herrera JP, Tempelmann C, Wolbers T. Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging. J Neurosci. 2021;41(14):3204-3221. https://doi.org/10.1523/jneurosci.0528-20.2021.
Zhu X, Han S, Geng Y, Ren W, Quan F. Brain-Derived Neurotrophic Factor-TrkB Pathway on Synaptic Plasticity in Ischemic Stroke Rats. Int Heart J. 2024;65(6):1095-1106. https://doi.org/10.1536/ihj.24-312.
Yang Y, Rao C, Yin T, Wang S, Shi H, Yan X, et al. Application and underlying mechanism of acupuncture for the nerve repair after peripheral nerve injury: remodeling of nerve system. Front Cell Neurosci. 2023;17: 1253438. https://doi.org/10.3389/fncel.2023.1253438.
Liu L, Liu M, Zhao W, Zhao YL, Wang Y. Tetrahydropalmatine Regulates BDNF through TrkB/CAM Interaction to Alleviate the Neurotoxicity Induced by Methamphetamine. ACS Chem Neurosci. 2021;12(18):3373-3386. https://doi.org/10.1021/acschemneuro.1c00373.
Castrén E, Monteggia LM. Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action. Biol Psychiatry. 2021;90(2):128-136. https://doi.org/10.1016/j.biopsych.2021.05.008.
Rauti R, Cellot G, D'Andrea P., Colliva A, Scaini D, Tongiorgi E, et al. BDNF impact on synaptic dynamics: extra or intracellular long-term release differently regulates cultured hippocampal synapses. Mol Brain. 2020;13(1):43. https://doi.org/10.1186/s13041-020-00582-9.
Li F, Xiang H, Gu Y, Ye T, Lu X, Huang C. Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice. J Neuroinflammation. 2022;19(1):12. https://doi.org/10.1186/12974-021-02377-8.
Simon GE, Moise N, Mohr DC. Management of Depression in Adults: A Review. JAMA. 2024;332(2):141-152. https://doi.org/10.1001/jama.2024.5756.
Jha MK, Mathew SJ. Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape. Am J Psychiatry. 2023;180(3):190-199. https://doi.org/10.1176/appi.ajp.20230025.
Sun Y, Hu N, Wang M, Lu L, Luo C, Tang B, et al. Hippocampal subfield alterations in schizophrenia and major depressive disorder: a systematic review and network meta-analysis of anatomic MRI studies. J Psychiatry Neurosci. 2023;48(1): E34-e49. https://doi.org/10.1503/jpn.220086.
Althammer F, Roy RK, Kirchner MK, Campos-Lira E, Whitley KE, Davis S, et al. Angiotensin II-Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats. Hypertension. 2023;80(6):1258-1273.https://doi.org/10.1161/HYPERTENSIONAHA.123.21070.
Nieto-Estévez V, Defterali Ç, Vicario C. Distinct Effects of BDNF and NT-3 on the Dendrites and Presynaptic Boutons of Developing Olfactory Bulb GABAergic Interneurons in Vitro. Cell Mol Neurobiol. 2022;42(5):1399-1417. https://doi.org/10.1007/s10571-020-01030-x. PMC11421695.
Sharma S, Chawla S, Kumar P, Ahmad R, Kumar Verma P. The chronic unpredictable mild stress (CUMS) Paradigm: Bridging the gap in depression research from bench to bedside. Brain Res. 2024;1843:149123. https://doi.org/10.1016/j.brainres.2024.149123.
Deng Y, Chen H, Huang Y, Zhang Y, Ren H, Fang M, et al. Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference. Environ Sci Technol. 2022;56(22):15805-15817. https://doi.org/10.1021/acs.est.1e07933.
Antoniuk S, Bijata M, Ponimaskin E, Włodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev. 2019;99: 101-116. https://doi.org/10.1016/j.neubiorev.2018.12.002.
Xie J, Ji J, Sun Y, Ma Y, Wu D, Zhang Z. Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system. J Hazard Mater. 2024;480: 136028. https://doi.org/10.1016/j.jhazmat.2024.136028.
Khataminezhad ES, Hajihassan Z, Razi Astaraei F. Magnetically purification/immobilization of polyhistidine-tagged proteins by PEGylated magnetic graphene oxide nanocomposites. Protein Expres Purif. 2023;207: 106264. https://doi.org/10.1016/j.pep.2023.106264.
Yang J, Li H, Hao Z, Jing X, Zhao Y, Cheng X, et al. Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway. ACS Appl Mater Interfaces. 2022;14(3):3685-3700. https://doi.org/10.1021/acsami.1c18417.
Shorey S, Ng ED, Wong CHJ. Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis. Br J Clin Psychol. 2022;61(2):287-305. https://doi.org/10.1111/bjc.12333.
Su Z, Kong R, Huang C, Wang K, Liu C, Gu X, et al. Exposure to polystyrene nanoplastics causes anxiety and depressive-like behavior and down-regulates EAAT2 expression in mice. Arch Toxicol. 2025;99(6):2595-2609. https://doi.org/10.1007/s00204-025-04002-6.
Wu C, Jia L, Mu Q, Fang Z, Hamoudi H, Huang M, et al. Altered hippocampal subfield volumes in major depressive disorder with and without anhedonia. BMC Psychiatry. 2023;23(1):540. https://doi.org/10.1186/s12888-023-05001-6.
Diersch N, Valdes-Herrera JP, Tempelmann C, Wolbers T. Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging. J Neurosci. 2021;41(14):3204-3221. https://doi.org/10.1523/jneurosci.0528-20.2021.
Zhu X, Han S, Geng Y, Ren W, Quan F. Brain-Derived Neurotrophic Factor-TrkB Pathway on Synaptic Plasticity in Ischemic Stroke Rats. Int Heart J. 2024;65(6):1095-1106. https://doi.org/10.1536/ihj.24-312.
Yang Y, Rao C, Yin T, Wang S, Shi H, Yan X, et al. Application and underlying mechanism of acupuncture for the nerve repair after peripheral nerve injury: remodeling of nerve system. Front Cell Neurosci. 2023;17: 1253438. https://doi.org/10.3389/fncel.2023.1253438.
Liu L, Liu M, Zhao W, Zhao YL, Wang Y. Tetrahydropalmatine Regulates BDNF through TrkB/CAM Interaction to Alleviate the Neurotoxicity Induced by Methamphetamine. ACS Chem Neurosci. 2021;12(18):3373-3386. https://doi.org/10.1021/acschemneuro.1c00373.
Castrén E, Monteggia LM. Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action. Biol Psychiatry. 2021;90(2):128-136. https://doi.org/10.1016/j.biopsych.2021.05.008.
Rauti R, Cellot G, D'Andrea P., Colliva A, Scaini D, Tongiorgi E, et al. BDNF impact on synaptic dynamics: extra or intracellular long-term release differently regulates cultured hippocampal synapses. Mol Brain. 2020;13(1):43. https://doi.org/10.1186/s13041-020-00582-9.
Publicado
2026-05-31
Cómo citar
Chang, D., Xu, M., Shi, W., He, Y., Wu, Z., Ning, Z., Sun , Y., & Lv, J. (2026). Neurotoxic effects of nanoplastics exposure on depression-like behavior and cognitive function in mice under chronic unpredictable mild stress.: Efectos neurotóxicos de la exposición a nanoplásticos sobre el comportamiento similar a la depresión y la función cognitiva en ratones sometidos a estrés crónico leve impredecible. Investigación Clínica, 67(2), 275-288. https://doi.org/10.54817/IC.v67n2a09
Sección
Trabajos Originales
