Effects of microplastics exposure on learning and memory in mice and its mechanism

JIANG Xin-Ze; LIU Qiang; SUN Xu; HOU Jiang-Shan; MA Rui; CHENG Mei; WU Yu-Long

doi:10.16098/j.issn.0529-1356.2024.05.004

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Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (5) : 541-546. DOI: 10.16098/j.issn.0529-1356.2024.05.004

Neurobiology

Effects of microplastics exposure on learning and memory in mice and its mechanism

JIANG Xin-ze¹ LIU Qiang² SUN Xu³ HOU Jiang-shan¹ MA Rui³ CHENG Mei^3* WU Yu-long^1* #br#

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Abstract

Objective To investigate the effect of microplastic (MPs) exposure on learning and memory in mice, and its mechanism by observing the protein expression of brain-derived neurotrophic factor (BDNF) /tyrosine receptor kinase B (TrkB) /N-methyl-D-aspartate receptor subtype 2B (NR2B) signaling pathway and neurogenesis. Methods Forty male C57BL/6 mice were randomly divided into control group (Ctrl) and microplastics exposure group (MPs). Mice in MPs group were treated with 0.3 mg/(kg·d) microplastics, administered by gavage at a volume of 200 μl for 30 consecutive days. Morris water maze test was used to evaluate the spatial learning and memory ability of mice. Western blotting was used to detect the protein levels of BDNF, TrkB and NR2B in hippocampus of mice. Immunofluorescent staining was used to observe the number of doublecortin (DCX) and neuronal nuclei antigen (NeuN) positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis. Results Compared with the control group, the ability of learning and memory decreased significantly in MPs group mice (P<0.01). The expression levels of BDNF, TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group (P<0.05). The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group (P<0.01). Conclusion MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis.

Key words

/ "> Microplastics｜Learning｜Memory｜Brain-derived neurotrophic factor｜Tyrosine receptor kinase B｜N-methyl-D-aspartate receptor subtype 2B｜Neurogenesis｜Western blotting｜Mouse

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JIANG Xin-ze LIU Qiang SUN Xu HOU Jiang-shan MA Rui CHENG Mei WU Yulong. Effects of microplastics exposure on learning and memory in mice and its mechanism[J]. Acta Anatomica Sinica. 2024, 55(5): 541-546 https://doi.org/10.16098/j.issn.0529-1356.2024.05.004

References

［1］ Upadhyay R, Singh S, Kaur G. Sorption of pharmaceuticals over microplastics’ surfaces: interaction mechanisms and governing factors［J］. Environ Monit Assess, 2022, 194(11): 803.
［2］ Galloway TS, Cole M, Lewis C. Interactions of microplastic debris throughout the marine ecosystem［J］. Nat Ecol Evol, 2017, 1(5): 116.
［3］ Alfonso MB, Arias AH, Ronda AC, et al. Continental microplastics: presence, features, and environmental transport pathways［J］. Sci Total Environ, 2021, 799: 149447.
［4］ Cox KD, Covernton GA, Davies HL, et al. Human consumption of microplastics［J］. Environ Sci Technol, 2019, 53(12):7068-7074.
［5］ Kutralam-Muniasamy G, Shruti VC, Pérez-Guevara F, et al. Microplastic diagnostics in humans: “The 3Ps” progress, problems, and prospects［J］. Sci Total Environ, 2023, 856(Pt 2): 159164.
［6］ Liu M, Liu J, Xiong F, et al. Research advances of microplastics and potential health risks of microplastics on terrestrial higher mammals: a bibliometric analysis and literature review［J］. Environ Geochem Health, 2023, 45(6): 2803-2838.
［7］ Geneva: World Health Organization. Microplastics in drinking-water ［EB/OL］. (2019-08-28) ［2020-05-27］. https://www.who.int/publications/i/item/9789241516198.
［8］ Wang S, Han Q, Wei Z, et al. Polystyrene microplastics affect learning and memory in mice by inducing oxidative stress and decreasing the level of acetylcholine［J］. Food Chem Toxicol, 2022, 162: 112904.
［9］ Ding YCh, Niu L, Xiao YH, et al. Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation［J］. Acta Anatomica Sinica, 2022, 53(2): 155-159. (in Chinese)
邓颖成,牛磊,肖玉花, 等.海马脑源性神经营养因子前体在社会隔离所致小鼠认知障碍中的作用［J］.解剖学报, 2022, 53(2): 155-159.
［10］ Wu Y, Deng F, Wang J, et al. Intensity-dependent effects of consecutive treadmill exercise on spatial learning and memory through the p-CREB/BDNF/NMDAR signaling in hippocampus［J］. Behav Brain Res, 2020, 386: 112599.
［11］ Caldeira MV, Melo CV, Pereira DB, et al. BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons［J］. Mol Cell Neurosci, 2007, 35(2): 208-219.
［12］ Itoh N, Enomoto A, Nagai T, et al. Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: the role of Girdin in the CNS［J］. Rev Neurosci, 2016, 27(5): 481-490.
［13］ Loftis JM, Janowsky A. The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications［J］. Pharmacol Ther, 2003, 97(1): 55-85.
［14］ Clayton DA, Mesches MH, Alvarez E, et al. A hippocampal NR2B deficit can mimic age-related changes in long-term potentiation and spatial learning in the Fischer 344 rat［J］. J Neurosci, 2002, 22(9): 3628-3637.
［15］ Lu L, Wan Z, Luo T, et al. Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice［J］. Sci Total Environ, 2018, 631-632:449-458.
［16］ Jin Y, Lu L, Tu W, et al. Impacts of polystyrene microplastic on the gut barrier, microbiota and metabolism of mice［J］. Sci Total Environ, 2019, 649: 308-317.
［17］ Jambeck JR, Geyer R, Wilcox C, et al. Marine pollution. Plastic waste inputs from land into the ocean［J］. Science, 2015, 347(6223):768-771.
［18］ Li RT, Lei LF, Yang N, et al. Impaired cholesterol metabolism affecting subventricular zone neurogenesis in ob/ob mice［J］. Acta Anatomica Sinica, 2023, 54(2): 165-174. (in Chinese)
李瑞婷,雷凌峰,杨娜, 等.胆固醇代谢障碍影响ob/ob小鼠室管膜下区神经发生［J］.解剖学报, 2023, 54(2): 165-174.
［19］ Talebian A, Robinson-Brookes K, Meakin SO. TrkB regulates N-Methyl-D-Aspartate receptor signaling by uncoupling and recruiting the brain-specific guanine nucleotide exchange factor, RasGrf1［J］. J Mol Neurosci, 2019, 67(1):97-110.
［20］ Tang YP, Shimizu E, Dube GR, et al. Genetic enhancement of learning and memory in mice［J］. Nature, 1999, 401(6748): 63-69.
［21］ Crozier RA, Black IB, Plummer MR. Blockade of NR2B-containing NMDA receptors prevents BDNF enhancement of glutamatergic transmission in hippocampal neurons［J］. Learn Mem, 1999, 6(3): 257-266.
［22］ Zhang Y, Sun Q, Fan A, et al. Isoflurane triggers the acute cognitive impairment of aged rats by damaging hippocampal neurons via the NR2B/CaMKII/CREB pathway［J］. Behav Brain Res, 2021, 405: 113202.
［23］ Alam MJ, Kitamura T, Saitoh Y, et al. Adult neurogenesis conserves hippocampal memory capacity［J］. J Neurosci, 2018, 38(31): 6854-6863.
［24］ Li YD, Luo YJ, Xie L, et al. Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease［J］. Cell Stem Cell, 2023, 30(4): 415-432. e6.
［25］ Santos D, Luzio A, Flix L, et al. Microplastics and copper induce apoptosis, alter neurocircuits, and cause behavioral changes in zebrafish (Danio rerio) brain［J］. Ecotoxicol Environ Saf, 2022, 242: 113926.