Neuroimmune Characteristics of Animals with Prenatal Alcohol Intoxication
- 作者: Shamakina I.Y.1, Anokhin P.K.1,2, Ageldinov R.A.3, Kokhan V.S.1
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隶属关系:
- Serbsky National Medical Research Center of Psychiatry and Narcology
- Artificial Intelligence Research Institute
- Scientific Center for Biomedical Technologies of the Federal Medical and Biological Agency of Russia
- 期: 卷 89, 编号 11 (2024)
- 页面: 1837-1846
- 栏目: Articles
- URL: https://rjeid.com/0320-9725/article/view/681416
- DOI: https://doi.org/10.31857/S0320972524110062
- EDN: https://elibrary.ru/IKSBEQ
- ID: 681416
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详细
Neuroinflammation can be an important factor of many central nervous system (CNS) deficits including cognitive dysfunction, affective disorders and addictive behavior associated with prenatal alcohol exposure and presented in early adulthood. In this study we used an experimental rodent model of prenatal alcohol (PA) exposure (consumption of a 10% ethanol solution by female Wistar rats throughout pregnancy), multiplex immunofluorescence analysis of interleukins (IL-1α, IL-1β, IL-3, IL-6, IL-9 and IL-12), tumor necrosis factor (TNF-α) and chemokine CCL5, as well as quantitative real-time PCR to assess the level of cytokine mRNA in the prefrontal cortex of sexually mature (PND60) offspring – male and female rats with prenatal alcohol intoxication and control animals. A significant decrease in the content of TNF-α and interleukins IL-1β, IL-3, IL-6, IL-9 was established in the prefrontal cortex of male, but not female PA offspring. Importantly, PA males also showed a decrease in the level of TNF-α mRNA in the prefrontal cortex by 45% compared to the control males, which may underlie a detected decrease in its content. Taken together, our study demonstrates that a number of neuroimmune factors are regulated in a sex-specific manner in the prefrontal cortex and are differentially affected in males and females by prenatal exposure to alcohol. Sex factor must be taken into account when conducting further translational fetal alcohol spectrum disorders and developing new methods for prevention and therapy.
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作者简介
I. Shamakina
Serbsky National Medical Research Center of Psychiatry and Narcology
编辑信件的主要联系方式.
Email: shamakina.i@serbsky.ru
俄罗斯联邦, 119002, Moscow
P. Anokhin
Serbsky National Medical Research Center of Psychiatry and Narcology; Artificial Intelligence Research Institute
Email: shamakina.i@serbsky.ru
俄罗斯联邦, 119002, Moscow; 121170, Moscow
R. Ageldinov
Scientific Center for Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Email: shamakina.i@serbsky.ru
俄罗斯联邦, 143442, Svetlye Gory
V. Kokhan
Serbsky National Medical Research Center of Psychiatry and Narcology
Email: shamakina.i@serbsky.ru
俄罗斯联邦, 119002, Moscow
参考
- Dejong, K., Olyaei, A., and Lo, J. O. (2019) Alcohol use in pregnancy, Clin. Obstet. Gynecol., 62, 142-155, https://doi.org/10.1097/GRF.0000000000000414.
- Jacobson, S. W., Hoyme, H. E., Carter, R. C., Dodge, N. C., Molteno, C. D., Meintjes, E. M., and Jacobson, J. L. (2021) Evolution of the physical phenotype of fetal alcohol spectrum disorders from childhood through adolescence, Alcohol. Clin. Exp. Res., 45, 395-408, https://doi.org/10.1111/acer.14534.
- Voutilainen, T., Rysä, J., Keski-Nisula, L., and Kärkkäinen, O. (2022) Self‐reported alcohol consumption of pregnant women and their partners correlates both before and during pregnancy: A cohort study with 21,472 singleton pregnancies, Alcohol. Clin. Exp. Res., 46, 797-808, https://doi.org/10.1111/acer.14806.
- Popova, S., Lange, S., Probst, C., Gmel, G., and Rehm, J. (2017) Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis, Lancet Glob. Health, 5, e290-e299, https://doi.org/10.1016/S2214-109X(17)30021-9.
- McQuire, C., Mukherjee, R., Hurt, L., Higgins, A., Greene, G., Farewell, D., Kemp, A., and Paranjothy, S. (2019) Screening prevalence of fetal alcohol spectrum disorders in a region of the United Kingdom: A populationbased birth-cohort study, Prev. Med., 118, 344-351, https://doi.org/10.1016/j.ypmed.2018.10.013.
- May, P. A., de Vries, M. M., Marais, A. S., Kalberg, W. O., Buckley, D., Hasken, J. M., Abdul-Rahman, O., Robinson, L. K., Manning, M. A., Seedat, S., Parry, C. D. H., and Hoyme, H. E. (2022) The prevalence of fetal alcohol spectrum disorders in rural communities in South Africa: A third regional sample of child characteristics and maternal risk factors, Alcohol. Clin. Exp. Res., 46, 1819-1836, https://doi.org/10.1111/ acer.14922.
- Astley, S. J., Bailey, D., Talbot, C., and Clarren, S. K. (2000) Fetal alcohol syndrome (FAS) primary prevention through fas diagnosis: II. A comprehensive profile of 80 birth mothers of children with FAS, Alcohol Alcohol., 35, 509-519, https://doi.org/10.1093/alcalc/35.5.509.
- Popova, S., Charness, M. E., Burd, L., Crawford, A., Hoyme, H. E., Mukherjee, R. A. S., Riley, E. P., and Elliott, E. J. (2023) Fetal alcohol spectrum disorders, Nat. Rev. Dis. Primers, 9, 11, https://doi.org/10.1038/s41572023-00420-x.
- Kautz-Turnbull, C., Rockhold, M., Handley, E. D., Olson, H. C., and Petrenko, C. (2023) Adverse childhood experiences in children with fetal alcohol spectrum disorders and their effects on behavior, Alcohol. Clin. Exp. Res., 47, 577-588, https://doi.org/10.1111/acer.15010.
- Nutt, D. J., Lingford-Hughes, A., Erritzoe, D., and Stokes, P. R. (2015) The dopamine theory of addiction: 40 years of highs and lows, Nat. Rev. Neurosci., 16, 305-312, https://doi.org/10.1038/nrn3939.
- Arreola, R., Alvarez-Herrera, S., Pérez-Sánchez, G., Becerril-Villanueva, E., Cruz-Fuentes, C., Flores-Gutierrez, E. O., Garcés-Alvarez, M. E., de la Cruz-Aguilera, D. L., Medina-Rivero, E., Hurtado-Alvarado, G., Quintero-Fabián, S., and Pavón, L. (2016) Immunomodulatory effects mediated by dopamine, J. Immunol. Res., 2016, 3160486, https://doi.org/10.1155/2016/3160486.
- Mladinov, M., Mayer, D., Brčic, L., Wolstencroft, E., Man, N., Holt, I., Hof, P. R., Morris, G. E., and Šimic, G. (2010) Astrocyte expression of D2-like dopamine receptors in the prefrontal cortex, Transl. Neurosci., 1, 238-243, https://doi.org/10.2478/v10134-010-0035-6.
- Albertini, G., Etienne, F., and Roumier, A. (2020) Regulation of microglia by neuromodulators: modulations in major and minor modes, Neurosci. Lett., 733, 135000, https://doi.org/10.1016/j.neulet.2020.135000.
- Feng, Y., and Lu, Y. (2021) Immunomodulatory effects of dopamine in inflammatory diseases, Front. Immunol., 12, 663102, https://doi.org/10.3389/fimmu.2021.663102.
- Iliopoulou, S. M., Tsartsalis, S., Kaiser, S., Millet, P., and Tournier, B. B. (2021) Dopamine and neuroinflammation in schizophrenia – interpreting the findings from translocator protein (18 kDa) PET imaging, Neuropsychiatr. Dis. Treat., 17, 3345-3357, https://doi.org/10.2147/NDT.S334027.
- Miller, A. H., Haroon, E., Raison, C. L., and Felger, J. C. (2013) Cytokine targets in the brain: impact on neurotransmitters and neurocircuits, Depress. Anxiety, 30, 297-306, https://doi.org/10.1002/da.22084.
- Abernathy, K., Chandler, L. J., and Woodward, J. J. (2010) Alcohol and the prefrontal cortex, Int. Rev. Neurobiol., 91, 289-320, https://doi.org/10.1016/S0074-7742(10)91009-X.
- Yamato, M., Tamura, Y., Eguchi, A., Kume, S., Miyashige, Y., Nakano, M., Watanabe, Y., and Kataoka, Y. (2014) Brain interleukin-1β and the intrinsic receptor antagonist control peripheral Toll-like receptor 3-mediated suppression of spontaneous activity in rats, PLoS One, 9, e90950, https://doi.org/10.1371/journal.pone.0090950.
- Lynch, M. A. (2002) Interleukin-1 beta exerts a myriad of effects in the brain and in particular in the hippocampus: analysis of some of these actions, Vitam. Horm., 64, 185-219, https://doi.org/10.1016/s0083-6729(02)64006-3.
- Deverman, B. E., and Patterson, P. H. (2009) Cytokines and CNS development, Neuron, 64, 61-78, https:// doi.org/10.1016/j.neuron.2009.09.002.
- Wei, H., Chadman, K. K., McCloskey, D. P., Sheikh, A. M., Malik, M., Brown, W. T., and Li, X. (2012) Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors, Biochim. Biophys. Acta, 1822, 831-842, https://doi.org/10.1016/j.bbadis.2012.01.011.
- Kondo, S., Kohsaka, S., and Okabe, S. (2011) Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo, Mol. Brain, 4, 27, https://doi.org/10.1186/1756-6606-4-27.
- Joseph, A. T., Bhardwaj, S. K., and Srivastava, L. K. (2018) Role of prefrontal cortex anti- and pro-inflammatory cytokines in the development of abnormal behaviors induced by disconnection of the ventral hippocampus in neonate rats, Front. Behav. Neurosci., 12, 244, https://doi.org/10.3389/fnbeh.2018.00244.
- Petitto, J. M., Meola, D., and Huang, Z. (2012) Interleukin-2 and the brain: dissecting central versus peripheral contributions using unique mouse models, Methods Mol. Biol., 934, 301-311, https://doi.org/10.1007/ 978-1-62703-071-7_15.
- Kamegai, M., Niijima, K., Kunishita, T., Nishizawa, M., Ogawa, M., Araki, M., Ueki, A., Konishi, Y., and Tabira, T. (1990) Interleukin-3 as a trophic factor for central cholinergic neurons in vitro and in vivo, Neuron, 2, 429-436.
- Fontaine, R. H., Cases, O., Lelièvre, V., Mesplès, B., Renauld, J. C., Loron, G., Degos, V., Dournaud, P., Baud, O., Gressens, P. (2008) IL-9/IL-9 receptor signaling selectively protects cortical neurons against developmental apoptosis, Cell Death Differ., 15, 1542-1552, https://doi.org/10.1038/cdd.2008.79.
- Lanfranco, M. F., Mocchetti, I., Burns, M. P., and Villapol, S. (2018) Glial- and neuronal-specific expression of CCL5 mRNA in the rat brain, Front. Neuroanat., 11, 137, https://doi.org/10.3389/fnana.2017.00137.
- Semple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M., and Noble-Haeusslein, L. J. (2013) Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species, Prog. Neurobiol., 106-107, 1-16, https://doi.org/10.1016/j.pneurobio.2013.04.001.
- Paxinos, G., and Watson, C. (1998) The Rat Brain in Stereotaxic Coordinates, 4th edn., New York, NY, Academic Press.
- Schmittgen, T. D., Livak, K. J. (2008) Analyzing real-time PCR data by the comparative C(T) method, Nat. Protoc., 3, 1101-1108, https://doi.org/10.1038/nprot.2008.73.
- Анохин П. К., Проскурякова Т. В., Шохонова В. А., Кохан В. С., Тарабарко И. Е., Шамакина И. Ю. (2023) Половые различия в аддиктивном поведении взрослых крыс: эффекты пренатальной алкоголизации, Биомедицина, 19, 27-36, https://doi.org/10.33647/2074-5982-19-2-27-36.
- Doremus-Fitzwater, T. L., Youngentob, S. L., Youngentob, L., Gano, A., Vore, A. S., and Deak, T. (2020) Lingering effects of prenatal alcohol exposure on basal and ethanol-evoked expression of inflammatory-related genes in the CNS of adolescent and adult rats, Front. Behav. Neurosci., 14, 82, https://doi.org/10.3389/fnbeh.2020.00082.
- Figiel, I. (2008) Pro-inflammatory cytokine TNF-alpha as a neuroprotective agent in the brain, Acta Neurobiol. Exp. (Wars.), 68, 526-534, https://doi.org/10.55782/ane-2008-1720.
- Gough, P., and Myles, I. A. (2020) Tumor necrosis factor receptors: pleiotropic signaling complexes and their differential effects, Front. Immunol., 11, 585880, https://doi.org/10.3389/fimmu.2020.585880.
- Papazian, I., Tsoukal, A. E., Boutou, A., Karamita, M., Kambas, K., Iliopoulou, L., Fischer, R., Kontermann, R. E, Denis, M. C., Kollias, G., Lassmann, H., and Probert, L. (2021) Fundamentally different roles of neuronal TNF receptors in CNS pathology: TNFR1 and IKKβ promote microglial responses and tissue injury in demyelination while TNFR2 protects against excitotoxicity in mice, J. Neuroinflammation, 18, 222, https://doi.org/10.1186/ s12974-021-02200-4.
- Базовкина Д. В. Фурсенко Д. В., Першина А. В., Хоцкин Н. В., Баженова Е. Ю., Куликов А. В. (2018) Влияние нокаута гена фактора некроза опухоли на поведение и дофаминовую систему мозга у мышей, Российский физиологический журнал им. И. М. Сеченова, 7, 745-756.
- Versele, R., Sevin, E., Gosselet, F., Fenart, L., and Candela, P. (2022) TNF-α and IL-1β modulate blood-brain barrier permeability and decrease amyloid-β peptide efflux in a human blood-brain barrier model, Int. J. Mol. Sci., 23, 10235, https://doi.org/10.3390/ijms231810235.
- Varodayan, F. P., Pahng, A. R., Davis, T. D., Gandhi, P., Bajo, M., Steinman, M. Q., Kiosses, W. B., Blednov, Y. A., Burkart, M. D., Edwards, S., Roberts, A. J., and Roberto, M. (2023) Chronic ethanol induces a pro-inflammatory switch in interleukin-1β regulation of GABAergic signaling in the medial prefrontal cortex of male mice, Brain Behav. Immun., 110, 125-139, https://doi.org/10.1016/j.bbi.2023.02.020.
- Koo, J. W., and Duman, R. S. (2009) Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory, Neurosci. Lett., 456, 39-43, https://doi.org/10.1016/j.neulet.2009.03.068.
- Jones, M., Lebonville, C., Barrus, D., and Lysle, D. T. (2015) The role of brain interleukin-1 in stress-enhanced fear learning, Neuropsychopharmacology, 40, 1289-1296, https://doi.org/10.1038/npp.2014.317.
- Gan, L., and Su, B. (2012) The interleukin 3 gene (IL3) contributes to human brain volume variation by regulating proliferation and survival of neural progenitors, PLoS One, 7, e50375, https://doi.org/10.1371/journal.pone.0050375.
- Zambrano, A., Otth, C., Mujica, L., Concha, I. I., and Maccioni, R. B. (2007) Interleukin-3 prevents neuronal death induced by amyloid peptide, BMC Neurosci., 8, 82, https://doi.org/10.1186/1471-2202-8-82.
- Donninelli, G., Saraf-Sinik, I., Mazziotti, V., Capone, A., Grasso, M. G., Battistini, L., Reynolds, R., Magliozzi, R., and Volpe, E. (2020) Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain, J. Neuroinflammation, 17, 149, https://doi.org/10.1186/s12974-020-01770-z.
- Meng, H., Niu, R., You, H., Wang, L., Feng, R., Huang, C., and Li, J. (2022) Interleukin-9 attenuates inflammatory response and hepatocyte apoptosis in alcoholic liver injury, Life Sci., 288, 120180, https://doi.org/10.1016/ j.lfs.2021.120180.
- Singhera, G. K., MacRedmond, R., and Dorscheid, D. R. (2008) Interleukin-9 and -13 inhibit spontaneous and corticosteroid induced apoptosis of normal airway epithelial cells, Exp. Lung Res., 34, 579-598.
- Erta, M., Quintana, A., and Hidalgo, J. (2012) Interleukin-6, a major cytokine in the central nervous system, Int. J. Biol. Sci., 8, 1254-1266, https://doi.org/10.7150/ijbs.4679.
- Hama, T., Kushima, Y., Miyamoto, M., Kubota, M., Takei, N., and Hatanaka, H. (1991) Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures, Neuroscience, 40, 445-452, https://doi.org/10.1016/0306-4522(91)90132-8.
- Mendonça Torres, P. M., and de Araujo, E. G. (2001) Interleukin-6 increases the survival of retinal ganglion cells in vitro, J. Neuroimmunol., 117, 43-50, https://doi.org/10.1016/s0165-5728(01)00303-4.
- Butterweck, V., Prinz, S., and Schwaninger, M. (2003) The role of interleukin-6 in stress-induced hyperthermia and emotional behaviour in mice, Behav. Brain Res., 144, 49-56, https://doi.org/10.1016/s0166-4328(03)00059-7.
- Balschun, D., Wetzel, W., Del Rey, A., Pitossi, F., Schneider, H., Zuschratter, W., and Besedovsky, H. O. (2004) Interleukin-6: a cytokine to forget, FASEB J., 18, 1788-1790, https://doi.org/10.1096/fj.04-1625fje.
- Mukherjee, S., Tarale, P., Sarkar, D. K. (2023) Neuroimmune interactions in fetal alcohol spectrum disorders: potential therapeutic targets and intervention strategies, Cells, 21, 2323, https://doi.org/10.3390/cells12182323.
- Айрапетов М. И., Ереско С. О., Бычков Е. Р., Лебедев А. А., Шабанов П. Д. (2021) Пренатальное воздействие алкоголя изменяет TLR4-опосредованную сигнализацию в префронтальной коре головного мозга у крыс, Биомедицинская химия, 67, 500-506, https://doi.org/10.18097/PBMC20216706500.
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