波谱学杂志 ›› 2025, Vol. 42 ›› Issue (4): 345-354.doi: 10.11938/cjmr20253146cstr: 32225.14.cjmr20253146
陈茜1,2, 刘思婕1,2, 蔡悦1,2, 程琳琳1,3, 王旭霞1,2, 康彦1,2, 林富春1,2, 雷皓1,2,3,*(
)
收稿日期:2025-02-19
出版日期:2025-12-05
在线发表日期:2025-04-08
通讯作者:
* Tel: 027-87198542, E-mail: leihao@wipm.ac.cn.
基金资助:
CHEN Xi1,2, LIU Sijie1,2, CAI Yue1,2, CHENG Linlin1,3, WANG Xuxia1,2, KANG Yan1,2, LIN Fuchun1,2, LEI Hao1,2,3,*(
)
Received:2025-02-19
Published:2025-12-05
Online:2025-04-08
Contact:
* Tel: 027-87198542, E-mail: leihao@wipm.ac.cn.
摘要:
近年来,青少年使用电子烟后出现癫痫发作的案例频现,引发了社会各界对尼古丁过量摄入潜在健康风险的深切关注.相较于成年人,青少年对尼古丁的强化效应更为敏感,且对其负面影响的耐受性更强,可能导致更高的尼古丁摄入量.研究表明,尼古丁具有诱发癫痫的潜在风险.现有临床研究主要关注尼古丁的成瘾性,而致痫剂量尼古丁对青少年大脑发育的影响仍缺乏系统研究.本研究探索了重复致痫剂量尼古丁腹腔注射对青少年雌性大鼠脑结构与行为的影响.结果表明,尼古丁暴露导致雌性大鼠海马dCA1/DG区域的灰质体积在短期和长期均增加.此外,尼古丁暴露诱发了海马dCA1/DG区域小胶质细胞的短期激活以及识别记忆功能的长期下降.
中图分类号:
陈茜, 刘思婕, 蔡悦, 程琳琳, 王旭霞, 康彦, 林富春, 雷皓. 致痫剂量尼古丁对青少年雌性大鼠海马结构的影响[J]. 波谱学杂志, 2025, 42(4): 345-354.
CHEN Xi, LIU Sijie, CAI Yue, CHENG Linlin, WANG Xuxia, KANG Yan, LIN Fuchun, LEI Hao. Effects of Seizure-inducing Doses Nicotine on Hippocampal Structure in Adolescent Female Rats[J]. Chinese Journal of Magnetic Resonance, 2025, 42(4): 345-354.
| [1] | JENSSEN B P, WALLEY S C, BOYKAN R, et al. Protecting children and adolescents from tobacco and nicotine[J]. Pediatrics, 2023, 151(5): e2023061806. |
| [2] |
DRZEWIECKI C M, JURASKA J M. The structural reorganization of the prefrontal cortex during adolescence as a framework for vulnerability to the environment[J]. Pharmacol Biochem Be, 2020, 199: 173044.
doi: 10.1016/j.pbb.2020.173044 |
| [3] |
COUNOTTE D S, SMIT A B, PATTIJ T, et al. Development of the motivational system during adolescence, and its sensitivity to disruption by nicotine[J]. Dev Cognit Neurosci, 2011, 1(4): 430-443.
doi: 10.1016/j.dcn.2011.05.010 |
| [4] |
BILSKY S A, LUBER M J, CLOUTIER R M, et al. Cigarette use, anxiety, and insomnia from adolescence to early adulthood: A longitudinal indirect effects test[J]. Addict Behav, 2021, 120: 106981.
doi: 10.1016/j.addbeh.2021.106981 |
| [5] | HAPPER J P, COURTNEY K E, BACA R E, et al. Nicotine use during late adolescence and young adulthood is associated with changes in hippocampal volume and memory performance[J]. Front Neurosci, 2024, 18: 1436951. |
| [6] |
COUNOTTE D S, GORIOUNOVA N A, LI K W, et al. Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence[J]. Nat Neurosci, 2011, 14(4): 417-419.
doi: 10.1038/nn.2770 pmid: 21336271 |
| [7] |
MATEOS B, BORCEL E, LORIGA R, et al. Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors[J]. J Psychopharmacol, 2011, 25(12): 1676-1690.
doi: 10.1177/0269881110370503 pmid: 20562169 |
| [8] |
PICKENS L R G, ROWAN J D, BEVINS R A, et al. Sex differences in adult cognitive deficits after adolescent nicotine exposure in rats[J]. Neurotoxicol Teratol, 2013, 38: 72-78.
doi: 10.1016/j.ntt.2013.05.001 pmid: 23673345 |
| [9] |
JACKLER R K, RAMAMURTHI D. Nicotine arms race: JUUL and the high-nicotine product market[J]. Tob Control, 2019, 28(6): 623-628.
doi: 10.1136/tobaccocontrol-2018-054796 pmid: 30733312 |
| [10] |
BENOWITZ N L. Seizures after vaping nicotine in youth: A canary or a red herring?[J]. J Adolescent Health, 2020, 66(1): 1-2.
doi: 10.1016/j.jadohealth.2019.10.016 |
| [11] |
SHAO X M, FANG Z T. Severe acute toxicity of inhaled nicotine and e-cigarettes[J]. Chest, 2020, 157(3): 506-508.
doi: 10.1016/j.chest.2019.10.008 |
| [12] |
FAULCON L M, RUDY S, LIMPERT J, et al. Adverse experience reports of seizures in youth and young adult electronic nicotine delivery systems users[J]. J Adolescent Health, 2020, 66(1): 15-17.
doi: 10.1016/j.jadohealth.2019.10.002 |
| [13] |
IHA H A, KUNISAWA N, SHIMIZU S, et al. Nicotine elicits convulsive seizures by activating amygdalar neurons[J]. Front Pharmacol, 2017, 8: 57.
doi: 10.3389/fphar.2017.00057 pmid: 28232801 |
| [14] |
MINER L L, MARKS M J, COLLINS A C. Relationship between nicotine-induced seizures and hippocampal nicotinic receptors[J]. Life Sci, 1985, 37(1): 75-83.
pmid: 4010471 |
| [15] | DJORDJEVIC M V, DORAN K A. Nicotine psychopharmacology[M]. Berlin, Heidelberg: Springer, 2009. |
| [16] |
GELLNER C A, BELLUZZI J D, LESLIE F M. Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats[J]. Neuropharmacology, 2016, 109: 247-253.
doi: S0028-3908(16)30279-9 pmid: 27346207 |
| [17] |
LEVIN E D, LAWRENCE S S, PETRO A, et al. Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates[J]. Neurotoxicol Teratol, 2007, 29(4): 458-465.
pmid: 17433619 |
| [18] |
DANNENHOFFER C A, SPEAR L P. Age differences in conditioned place preferences and taste aversions to nicotine[J]. Dev Psychobiol, 2016, 58(5): 660-666.
doi: 10.1002/dev.21400 pmid: 27027859 |
| [19] |
TORRES O V, TEJEDA H A, NATIVIDAD L A, et al. Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development[J]. Pharmacol Biochem Be, 2008, 90(4): 658-663.
doi: 10.1016/j.pbb.2008.05.009 pmid: 18571223 |
| [20] |
PICCIOTTO M R. Nicotine as a modulator of behavior: beyond the inverted U[J]. Trends Pharmacol Sci, 2003, 24(9): 493-499.
pmid: 12967775 |
| [21] | HU Y D, CAI Y, WANG X X, et al. Magnetic resonance imaging the brain structures involved in nicotine susceptibility in rats[J]. Chinese J Magn Reson, 2021, 38(3): 345-355. |
|
胡赢丹, 蔡悦, 王旭霞, 等. 尼古丁易感的脑结构特征的磁共振成像研究[J]. 波谱学杂志, 2021, 38(3): 345-355.
doi: 10.11938/cjmr20212890 |
|
| [22] |
MINER L L, COLLINS A C. Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors[J]. Pharmacol Biochem Be, 1989, 33(2): 469-475.
pmid: 2813485 |
| [23] |
HILLERT M H, IMRAN I, ZIMMERMANN M, et al. Dynamics of hippocampal acetylcholine release during lithium-pilocarpine-induced status epilepticus in rats[J]. J Neurochem, 2014, 131(1): 42-52.
doi: 10.1111/jnc.12787 pmid: 24909269 |
| [24] |
LIETSCHE J, IMRAN I, KLEIN J. Extracellular levels of ATP and acetylcholine during lithium-pilocarpine induced status epilepticus in rats[J]. Neurosci Lett, 2016, 611: 69-73.
doi: 10.1016/j.neulet.2015.11.028 pmid: 26610905 |
| [25] | ZAPUKHLIAK O, NETSYK O, ROMANOV A, et al. Mecamylamine inhibits seizure-like activity in CA1-CA3 hippocampus through antagonism to nicotinic receptors[J]. PLoS One, 2021, 16(3): e0240074. |
| [26] |
CHEN X, LONG K, LIU S, et al. Repeated exposure to high-dose nicotine induces prefrontal gray matter atrophy in adolescent male rats[J]. Neuroscience, 2024, 566: 205-217.
doi: 10.1016/j.neuroscience.2024.11.059 |
| [27] |
GOMES P X L, DE OLIVEIRA G V, DE ARAÚJO F Y R, et al. Differences in vulnerability to nicotine-induced kindling between female and male periadolescent rats[J]. Psychopharmacol, 2013, 225(1): 115-126.
doi: 10.1007/s00213-012-2799-5 |
| [28] |
TRAUTH J A, SEIDLER F J, SLOTKIN T A. An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions[J]. Brain Res, 2000, 867(1-2): 29-39.
pmid: 10837795 |
| [29] |
XU Z, SEIDLER F J, TATE C A, et al. Sex-selective hippocampal alterations after adolescent nicotine administration: Effects on neurospecific proteins[J]. Nicotine Tob Res, 2003, 5(6): 955-960.
pmid: 14668080 |
| [30] |
SPEAR L P. The adolescent brain and age-related behavioral manifestations[J]. Neurosci Biobehav Rev, 2000, 24(4): 417-463.
doi: 10.1016/s0149-7634(00)00014-2 pmid: 10817843 |
| [31] |
EHLINGER D G, BERGSTROM H C, BURKE J C, et al. Adolescent nicotine-induced dendrite remodeling in the nucleus accumbens is rapid, persistent, and D1-dopamine receptor dependent[J]. Brain Struct Funct, 2016, 221(1): 133-145.
doi: 10.1007/s00429-014-0897-3 pmid: 25257604 |
| [32] |
COUNOTTE D S, SPIJKER S, VAN DE BURGWAL L H, et al. Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats[J]. Neuropsychopharmacology, 2009, 34(2): 299-306.
doi: 10.1038/npp.2008.96 pmid: 18580873 |
| [33] |
CANO M, REYNAGA D D, BELLUZZI J D, et al. Chronic exposure to cigarette smoke extract upregulates nicotinic receptor binding in adult and adolescent rats[J]. Neuropharmacology, 2020, 181: 108308.
doi: 10.1016/j.neuropharm.2020.108308 |
| [34] |
JÓSÊ A S, FRANCISCATO C, SÔNEGO F, et al. Sensitivity of young rats to nicotine exposure: Physiological and biochemical parameters[J]. Ecotox Environ Safe, 2009, 72(1): 242-247.
doi: S0147-6513(08)00095-X pmid: 18462794 |
| [35] | OVIE F O, AKPUAKA F C, NDUKWE G U, et al. Effect of cigarette smoke inhalation on the hippocampus of adult female wistar rat[J]. Asian J Med Princ Clin Pract, 2021, 4(2): 321-326. |
| [36] |
ASAN L, FALFÁN-MELGOZA C, BERETTA C A, et al. Cellular correlates of gray matter volume changes in magnetic resonance morphometry identified by two-photon microscopy[J]. Sci Rep, 2021, 11(1): 4234.
doi: 10.1038/s41598-021-83491-8 pmid: 33608622 |
| [37] |
WU H, WANG X, GAO Y, et al. NMDA receptor antagonism by repetitive MK801 administration induces schizophrenia-like structural changes in the rat brain as revealed by voxel-based morphometry and diffusion tensor imaging[J]. Neuroscience, 2016, 322: 221-233.
doi: 10.1016/j.neuroscience.2016.02.043 pmid: 26917273 |
| [38] | HUANG W, CAO Z Y. STZ-induced progressive brain atrophy studied by magnetic resonance imaging and histochemical staining[J]. Chinese J Magn Reson, 2015, 32(3): 439-449. |
|
黄微, 曹子玉. STZ诱导大鼠1型糖尿病进行性脑萎缩的磁共振成像及组织化学研究[J]. 波谱学杂志, 2015, 32(3): 439-449.
doi: 10.11938/cjmr20150305 |
|
| [39] |
ABREU-VILLAÇA Y, SEIDLER F J, TATE C A, et al. Nicotine is a neurotoxin in the adolescent brain: critical periods, patterns of exposure, regional selectivity, and dose thresholds for macromolecular alterations[J]. Brain Res, 2003, 979(1-2): 114-128.
doi: 10.1016/S0006-8993(03)02885-3 |
| [40] |
SHINGO A S, KITO S. Effects of nicotine on neurogenesis and plasticity of hippocampal neurons[J]. J Neural Transm, 2005, 112(11): 1475-1478.
pmid: 16245069 |
| [41] |
BRUIJNZEEL A W, BAUZO R M, MUNIKOTI V, et al. Tobacco smoke diminishes neurogenesis and promotes gliogenesis in the dentate gyrus of adolescent rats[J]. Brain Res, 2011, 1413: 32-42.
doi: 10.1016/j.brainres.2011.07.041 pmid: 21840504 |
| [42] |
POLESSKAYA O O, FRYXELL K J, MERCHANT A D, et al. Nicotine causes age-dependent changes in gene expression in the adolescent female rat brain[J]. Neurotoxicol Teratol, 2007, 29(1): 126-140.
pmid: 17234382 |
| [43] |
ROMANO E, DE ANGELIS F, ULBRICH L, et al. Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice[J]. Psychopharmacol, 2014, 231(8): 1775-1787.
doi: 10.1007/s00213-013-3388-y |
| [44] |
SCHOCHET T L, KELLEY A E, LANDRY C F. Differential expression of Arc mRNA and other plasticity-related genes induced by nicotine in adolescent rat forebrain[J]. Neuroscience, 2005, 135(1): 285-297.
pmid: 16084664 |
| [45] |
SMITH R F, MCDONALD C G, BERGSTROM H C, et al. Adolescent nicotine induces persisting changes in development of neural connectivity[J]. Neurosci Biobehav Rev, 2015, 55: 432-443.
doi: 10.1016/j.neubiorev.2015.05.019 pmid: 26048001 |
| [46] |
HOLLIDAY E D, NUCERO P, KUTLU M G, et al. Long-term effects of chronic nicotine on emotional and cognitive behaviors and hippocampus cell morphology in mice: comparisons of adult and adolescent nicotine exposure[J]. Eur J Neurosci, 2016, 44(10): 2818-2828.
doi: 10.1111/ejn.13398 pmid: 27623427 |
| [47] |
PAOLICELLI R C, BOLASCO G, PAGANI F, et al. Synaptic pruning by microglia is necessary for normal brain development[J]. Science, 2011, 333(6048): 1456-1458.
doi: 10.1126/science.1202529 pmid: 21778362 |
| [48] |
PARKHURST C N, YANG G, NINAN I, et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor[J]. Cell, 2013, 155(7): 1596-1609.
doi: 10.1016/j.cell.2013.11.030 pmid: 24360280 |
| [49] |
MAHAJAN S D, HOMISH G G, QUISENBERRY A. Multifactorial etiology of adolescent nicotine addiction: A review of the neurobiology of nicotine addiction and its implications for smoking cessation pharmacotherapy[J]. Front Public Health, 2021, 9: 664748.
doi: 10.3389/fpubh.2021.664748 |
| [50] |
LINKER K E, ELABD M G, TAWADROUS P, et al. Microglial activation increases cocaine self-administration following adolescent nicotine exposure[J]. Nat Commun, 2020, 11(1): 306.
doi: 10.1038/s41467-019-14173-3 pmid: 31949158 |
| [51] |
KOMORI T, OKAMURA K, IKEHARA M, et al. Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior[J]. Mol Psychiatry, 2024, 29(5): 1338-1349.
doi: 10.1038/s41380-024-02413-y |
| [1] | 马滢雪, 赵晏强, 杨晓冬, 蒋滨, 陶诚. 我国高场及超高场磁共振成像设备研制和市场化的机遇与挑战[J]. 波谱学杂志, 2025, 42(3): 334-344. |
| [2] | 魏志宏, 孔旭东, 孔燕, 闫士举, 丁阳, 魏贤顶, 孔栋, 杨波. 基于全局和局部特征信息的生成对抗网络在海马体分割中的应用[J]. 波谱学杂志, 2025, 42(2): 143-153. |
| [3] | 逄奇凡, 王志超, 武玉朋, 李建奇. K空间填充策略对基于FLASH序列的APT图像脂肪伪影的影响[J]. 波谱学杂志, 2024, 41(4): 443-453. |
| [4] | 徐真顺, 袁小涵, 黄子珩, 邵成伟, 武杰, 边云. 基于深度学习的胰腺黏液性和浆液性囊性肿瘤的多源特征分类模型[J]. 波谱学杂志, 2024, 41(1): 19-29. |
| [5] | 徐慧, 吴伊婷, 王旭霞, 康彦, 雷皓, 高丽凤. 1H MRS评价长期胰岛素治疗1型糖尿病大鼠海马代谢物的变化[J]. 波谱学杂志, 2022, 39(4): 393-400. |
| [6] | 唐德港,李红闯,刘小玲,石磊,李海东,叶朝辉,周欣. 1.5 T下高介电材料几何结构对发射场影响的仿真研究[J]. 波谱学杂志, 2022, 39(2): 155-162. |
| [7] | 王振宇, 王颖珊, 毛瑾玲, 马伟伟, 路青, 石洁, 汪红志. 基于Dense-UNet++的关节滑膜磁共振图像分割[J]. 波谱学杂志, 2022, 39(2): 208-219. |
| [8] | 马岩, 邢藏菊, 肖亮. 基于级联网络的膝关节图像分割与模型构建[J]. 波谱学杂志, 2022, 39(2): 184-195. |
| [9] | 骆俊, 刘盛平, 杨兴, 王佳升, 李烨. 一种无磁化的5 T磁共振射频功率放大器设计[J]. 波谱学杂志, 2022, 39(2): 163-173. |
| [10] | 张菊敏,陈世桢,周欣. 基于动态有机钆纳米颗粒的T1-T2双模态MRI造影剂[J]. 波谱学杂志, 2022, 39(1): 11-19. |
| [11] | 王志超,张记磊,赵羽,华婷,汤光宇,李建奇. 基于神经网络拟合的腹部化学交换饱和转移成像[J]. 波谱学杂志, 2022, 39(1): 33-42. |
| [12] | 王瀚苇,吴昊,田静,张俊峰,钟鹏,陈立朝,王舒楠. T2/FLAIR错配征的定量参数在评价较低级别胶质瘤分子分型的诊断价值[J]. 波谱学杂志, 2022, 39(1): 56-63. |
| [13] | 肖龙,朱筱磊,韩叶清,陈世桢,周欣. 胶束型磁共振成像分子探针的设计与应用[J]. 波谱学杂志, 2021, 38(4): 474-490. |
| [14] | 胡赢丹,蔡悦,王旭霞,刘思婕,康彦,雷皓,林富春. 尼古丁易感的脑结构特征的磁共振成像研究[J]. 波谱学杂志, 2021, 38(3): 345-355. |
| [15] | 闫士举,韩勇森,汤光宇. 一种用于前列腺区域分割的改进水平集算法[J]. 波谱学杂志, 2021, 38(3): 356-366. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||