Research Article
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Lipopolisakkarit ile indüklenen nöroinflamasyon modelinde köşe dönme testinde dönüş tercihleri ve sağ-sol beyin hemisferlerinde proinflamatuar sitokinlerin durumu

Year 2025, Volume: 8 Issue: 4 , 640 - 645 , 30.07.2025
https://doi.org/10.32322/jhsm.1691744
https://izlik.org/JA58PS52UL

Abstract

Amaç: Nöroinflamasyon, sinir sistemi içindeki enflamatuar bir tepki olarak tanımlanır. Bu çalışmada, lipopolisakkarit ile indüklenen nöroinflamasyon modelinde köşe dönme testinde sıçanların davranışları ve sağ/sol hemisferler arasında proinflamatuar sitokinlerin dağılımı incelenmiştir. Ayrıca, lokomotor aktivite, anksiyete benzeri davranışlar ve stresle ilişkili harder bezi salgısı da analiz edilmiştir.

Yöntemler: 12 yetişkin erkek Wistar Albino sıçan kontrol (n=6) ve nöroinflamasyon (n=6) gruplarına ayrıldı. Nöroinflamasyon grubuna tek doz 2 mg/kg intraperitoneal LPS, kontrol grubuna ise 1 ml/kg fizyolojik salin uygulandı. LPS uygulamasından 6 saat sonra 5 dakikalık açık alan testi yapıldı. Köşe dönüş testi protokolü LPS uygulamasından 6 ve 24 saat sonra uygulandı. Denekler, LPS uygulamasından 24 saat sonra öldürüldü. TNF-a ve IL-1beta, prefrontal korteks, striatum ve serumda analiz edildi. Tüm prosedürler Balıkesir Üniversitesi Deney Hayvanları Etik Kurulu'nun onayıyla (onay numarası 2023/10-5) gerçekleştirildi. Sonuçlar, öğrencilerin t-testi kullanılarak analiz edildi.

Bulgular: Açık alan testinde, lokomotor aktivite azalırken (p<0,0001), anksiyete benzeri davranışlar artmıştır (p<0,05-p<0,0001). Harderian bezi salgısı, nöroinflamasyon grubunda 4-5 puanlık bir artışla anlamlı olarak artmıştır (p<0,0001). Köşe dönme testinde kontrol ve LPS grupları arasında fark gözlenmedi (p>0,05). TNF-alfa ve IL-1beta, kontrol grubuna kıyasla önemli ölçüde arttı (p<0,01-p<0,0001). Sağ hemisferler arasında proinflamatuar sitokinlerde fark yoktu (p>0,01).
Sonuç: Nöroinflamasyon grubunda anksiyete benzeri davranışlar ve proinflamatuar sitokinler artmıştır. Göz ve burun çevresinde stresle ilişkili lekelenme artmıştır. Köşe dönme testine göre, anlamlı bir fark gözlenmemiştir. Nörolojik deneylerde hemisferlere verilen hasarı inceleyen köşe dönme testi ile nöroinflamasyon modellerinde daha fazla çalışma yapılması gerekmektedir.

References

  • Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-435. doi:10.1038/nature07201
  • Calder PC, Albers R, Antoine JM, et al. Inflammatory disease processes and interactions with nutrition. Br J Nutr. 2009;101(Suppl 1):S1-45. doi: 10.1017/S0007114509377867
  • Bennett JM, Reeves G, Billman GE, Sturmberg JP. Inflammation-nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front Med (Lausanne). 2018;5:316. doi:10.3389/fmed.2018.00316
  • DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(Suppl 2):136-153. doi:10.1111/jnc. 13607
  • Davalos D, Grutzendler J, Yang G, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8(6):752-758. doi:10.1038/nn1472
  • Sperandeo P, Dehò G, Polissi A. The lipopolysaccharide transport system of gram-negative bacteria. Biochim Biophys Acta. 2009;1791(7):594-602. doi:10.1016/j.bbalip.2009.01.011
  • Çalışkan H, Önal D, Nalçacı E. Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats. BMC Immunol. 2024; 25(1):75. doi:10.1186/s12865-024-00665-5
  • Arab Z, Hosseini M, Mashayekhi F, Anaeigoudari A. Zataria multiflora extract reverses lipopolysaccharide-induced anxiety and depression behaviors in rats. Avicenna J Phytomed. 2020;10(1):78-88.
  • Jain NK, Patil CS, Kulkarni SK, Singh A. Modulatory role of cyclooxygenase inhibitors in aging- and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice. Behav Brain Res. 2002;133(2):369-376. doi:10.1016/s0166-4328(02)00025-6
  • Lai YT, Tsai YP, Cherng CG, et al. Lipopolysaccharide mitagates methamphetamine-induced striatal dopamine depletion via modulating local TNF-alpha and dopamine transporter expression. J Neural Transm (Vienna). 2009;116(4):405-415. doi:10.1007/s00702-009-0204-2
  • Kwatra M, Ahmed S, Gawali B, Panda SR, Naidu V. Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced hippocampus and frontal cortex damage in mice: role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling. Neurochem Int. 2020;140:104835. doi:10.1016/j.neuint.2020.104835
  • Hua Y, Schallert T, Keep RF, Wu J, Hoff JT, Xi G. Behavioral tests after intracerebral hemorrhage in the rat. Stroke. 2002;33(10):2478-2484. doi: 10.1161/01.str.0000032302.91894.0f
  • Balkaya M, Kröber JM, Rex A, Endres M. Assessing post-stroke behavior in mouse models of focal ischemia. J Cereb Blood Flow Metab. 2013;33(3): 330-338. doi:10.1038/jcbfm.2012.185
  • Çalışkan H, Karakaya D, Koçak S, Ömercioğlu G, Baştuğ M. Effect of high-intensity interval training on self-care and anxiety-like behaviors in naive rats. Exp Brain Res. 2024;242(4):913-920. doi:10.1007/s00221-024-06793-z
  • McBride DW, Wang Y, Sherchan P, Tang J, Zhang JH. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats. Behav Brain Res. 2015;290:161-171. doi:10. 1016/j.bbr.2015.05.001
  • Burn CC, Peters A, Day MJ, Mason GJ. Long-term effects of cage-cleaning frequency and bedding type on laboratory rat health, welfare, and handleability: a cross-laboratory study. Lab Anim. 2006;40(4):353-370. doi:10.1258/002367706778476460
  • Paxinos G, Watson C. The rat brain in stereotaxic coordinates: hard cover edition. Elsevier. 2006.
  • Değirmenci MD, Çalışkan H, Güneş E. Effects of chronic intermittent cold stress on anxiety-depression-like behaviors in adolescent rats. Behav Brain Res. 2024;472:115130. doi:10.1016/j.bbr.2024.115130
  • Moraes MM, Galvão MC, Cabral D, et al. Propentofylline prevents sickness behavior and depressive-like behavior induced by lipopolysaccharide in rats via neuroinflammatory pathway. PLoS One. 2017;12(1):e0169446. doi:10.1371/journal.pone.0169446
  • Beheshti F, Hashemzehi M, Hosseini M, Marefati N, Memarpour S. Inducible nitric oxide synthase plays a role in depression- and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: evidence from inflammation and oxidative stress. Behav Brain Res. 2020;392:112720. doi:10.1016/j.bbr.2020.112720
  • Shentu Y, Tian Q, Yang J, et al. Upregulation of KDM6B contributes to lipopolysaccharide-induced anxiety-like behavior via modulation of VGLL4 in mice. Behav Brain Res. 2021;408:113305. doi:10.1016/j.bbr. 2021.113305
  • Wu Y, Qiu A, Yang Z, et al. Malva sylvestris extract alleviates the astrogliosis and inflammatory stress in LPS-induced depression mice. J Neuroimmunol. 2019;336:577029. doi:10.1016/j.jneuroim.2019.577029
  • Spohr L, Luduvico KP, Soares MSP, et al. Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide. Nutr Neurosci. 2022;25(4):857-870. doi:10.1080/1028415X.2020.1819104
  • Berg BM, Godbout JP, Chen J, Kelley KW, Johnson RW. Alpha-tocopherol and selenium facilitate recovery from lipopolysaccharide-induced sickness in aged mice. J Nutr. 2005;135(5):1157-1163. doi:10. 1093/jn/135.5.1157
  • Altar CA, Cai N, Bliven T, et al. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature. 1997;389(6653):856-860. doi:10.1038/39885
  • Du J, An J, Wei N, Guan T, Pritchard KA Jr, Shi Y. Increased resistance to LPS-induced myocardial dysfunction in the Brown Norway rats versus Dahl S rats: roles of inflammatory cytokines and nuclear factor kappa B pathway. Shock. 2010;33(3):332-336. doi:10.1097/SHK.0b013e3181b7819e
  • Koc F, Tekeli MY, Kanbur M, Karayigit MÖ, Liman BC. The effects of chrysin on lipopolysaccharide-induced sepsis in rats. J Food Biochem. 2020;44(9):e13359. doi:10.1111/jfbc.13359
  • Reyes EP, Abarzúa S, Martin A, Rodríguez J, Cortés PP, Fernández R. LPS-induced c-Fos activation in NTS neurons and plasmatic cortisol increases in septic rats are suppressed by bilateral carotid chemodenervation. Adv Exp Med Biol. 2012;758:185-190. doi:10.1007/ 978-94-007-4584-1_26
  • Ribeiro DE, Maiolini VM, Soncini R, et al. Inhibition of nitric oxide synthase accentuates endotoxin-induced sickness behavior in mice. Pharmacol Biochem Behav. 2013;103(3):535-540. doi:10.1016/j.pbb.2012. 09.022
  • Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019;10(2):128. doi:10.1038/s41419-019-1413-8

Turning preferences in the corner turning test and the status of proinflammatory cytokines in the right-left brain hemispheres in the lipopolysaccharide-induced neuroinflammation model

Year 2025, Volume: 8 Issue: 4 , 640 - 645 , 30.07.2025
https://doi.org/10.32322/jhsm.1691744
https://izlik.org/JA58PS52UL

Abstract

Aims: Neuroinflammation is described as an inflammatory response within the nervous system. The study aimed to investigate the behavior of rats in the corner turning test and the distribution of proinflammatory cytokines between the right/left hemispheres in the neuroinflammation model induced by lipopolysaccharide. Furthermore, locomotor activity, anxiety-like behaviors, and stress-related harderian gland secretion were also analyzed.
Methods: 12 adults male Wistar albino rats were divided into control (n=6) and neuroinflammation animals (n=6). The neuroinflammation group received a single dose of 2 mg/kg intraperitoneally LPS, and 1 ml/kg physiological saline was administered to the control group. Six hours after LPS administration, open field test was performed for 5 minutes. The corner rotation test protocol was performed 6 and 24 hours after LPS administration. Subjects were sacrificed 24 hours after LPS administration. TNF-a and IL-1beta were analyzed in the prefrontal cortex, striatum, and serum. All procedures were conducted with the approval of the Balıkesir University Experimental Animals Ethics Committee (Date: 22.11.2023, Decision No: 2023/10-5). Results were analyzed using the students’ T test.
Results: In the open field test, locomotor activity decreased (p<0.0001), while anxiety-like behaviors increased (p<0.05-p<0.0001). Harderian gland secretion significantly increased by 4-5 points in the neuroinflammation group (p<0.0001). No difference was observed between the control and LPS groups in the corner-turning test (p>0.05). TNF-alpha and IL-1beta significantly increased compared to the control group (p<0.01-p<0.0001). There was no difference in proinflammatory cytokines between the right hemispheres (p>0.01).
Conclusion: In the neuroinflammation group, anxiety-like behaviors and proinflammatory cytokines increased. Stress-related spotting around the eyes and nose increased. According to the corner-turning test, no significant difference was observed. More studies are needed in neuroinflammation models with the corner-turning test, which examines damage to the hemispheres in neurological experiments.

Ethical Statement

The Animal Experiments Local Ethics Committee of Balıkesir University approved this study (Decision No: 2023/10-5).

Thanks

We want to thank Dr. Vet. Dr. Mustafa Hilmi Yaranoğlu and Health Technician Mehmet Bozdemir for their help in providing animals.

References

  • Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-435. doi:10.1038/nature07201
  • Calder PC, Albers R, Antoine JM, et al. Inflammatory disease processes and interactions with nutrition. Br J Nutr. 2009;101(Suppl 1):S1-45. doi: 10.1017/S0007114509377867
  • Bennett JM, Reeves G, Billman GE, Sturmberg JP. Inflammation-nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front Med (Lausanne). 2018;5:316. doi:10.3389/fmed.2018.00316
  • DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(Suppl 2):136-153. doi:10.1111/jnc. 13607
  • Davalos D, Grutzendler J, Yang G, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8(6):752-758. doi:10.1038/nn1472
  • Sperandeo P, Dehò G, Polissi A. The lipopolysaccharide transport system of gram-negative bacteria. Biochim Biophys Acta. 2009;1791(7):594-602. doi:10.1016/j.bbalip.2009.01.011
  • Çalışkan H, Önal D, Nalçacı E. Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats. BMC Immunol. 2024; 25(1):75. doi:10.1186/s12865-024-00665-5
  • Arab Z, Hosseini M, Mashayekhi F, Anaeigoudari A. Zataria multiflora extract reverses lipopolysaccharide-induced anxiety and depression behaviors in rats. Avicenna J Phytomed. 2020;10(1):78-88.
  • Jain NK, Patil CS, Kulkarni SK, Singh A. Modulatory role of cyclooxygenase inhibitors in aging- and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice. Behav Brain Res. 2002;133(2):369-376. doi:10.1016/s0166-4328(02)00025-6
  • Lai YT, Tsai YP, Cherng CG, et al. Lipopolysaccharide mitagates methamphetamine-induced striatal dopamine depletion via modulating local TNF-alpha and dopamine transporter expression. J Neural Transm (Vienna). 2009;116(4):405-415. doi:10.1007/s00702-009-0204-2
  • Kwatra M, Ahmed S, Gawali B, Panda SR, Naidu V. Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced hippocampus and frontal cortex damage in mice: role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling. Neurochem Int. 2020;140:104835. doi:10.1016/j.neuint.2020.104835
  • Hua Y, Schallert T, Keep RF, Wu J, Hoff JT, Xi G. Behavioral tests after intracerebral hemorrhage in the rat. Stroke. 2002;33(10):2478-2484. doi: 10.1161/01.str.0000032302.91894.0f
  • Balkaya M, Kröber JM, Rex A, Endres M. Assessing post-stroke behavior in mouse models of focal ischemia. J Cereb Blood Flow Metab. 2013;33(3): 330-338. doi:10.1038/jcbfm.2012.185
  • Çalışkan H, Karakaya D, Koçak S, Ömercioğlu G, Baştuğ M. Effect of high-intensity interval training on self-care and anxiety-like behaviors in naive rats. Exp Brain Res. 2024;242(4):913-920. doi:10.1007/s00221-024-06793-z
  • McBride DW, Wang Y, Sherchan P, Tang J, Zhang JH. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats. Behav Brain Res. 2015;290:161-171. doi:10. 1016/j.bbr.2015.05.001
  • Burn CC, Peters A, Day MJ, Mason GJ. Long-term effects of cage-cleaning frequency and bedding type on laboratory rat health, welfare, and handleability: a cross-laboratory study. Lab Anim. 2006;40(4):353-370. doi:10.1258/002367706778476460
  • Paxinos G, Watson C. The rat brain in stereotaxic coordinates: hard cover edition. Elsevier. 2006.
  • Değirmenci MD, Çalışkan H, Güneş E. Effects of chronic intermittent cold stress on anxiety-depression-like behaviors in adolescent rats. Behav Brain Res. 2024;472:115130. doi:10.1016/j.bbr.2024.115130
  • Moraes MM, Galvão MC, Cabral D, et al. Propentofylline prevents sickness behavior and depressive-like behavior induced by lipopolysaccharide in rats via neuroinflammatory pathway. PLoS One. 2017;12(1):e0169446. doi:10.1371/journal.pone.0169446
  • Beheshti F, Hashemzehi M, Hosseini M, Marefati N, Memarpour S. Inducible nitric oxide synthase plays a role in depression- and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: evidence from inflammation and oxidative stress. Behav Brain Res. 2020;392:112720. doi:10.1016/j.bbr.2020.112720
  • Shentu Y, Tian Q, Yang J, et al. Upregulation of KDM6B contributes to lipopolysaccharide-induced anxiety-like behavior via modulation of VGLL4 in mice. Behav Brain Res. 2021;408:113305. doi:10.1016/j.bbr. 2021.113305
  • Wu Y, Qiu A, Yang Z, et al. Malva sylvestris extract alleviates the astrogliosis and inflammatory stress in LPS-induced depression mice. J Neuroimmunol. 2019;336:577029. doi:10.1016/j.jneuroim.2019.577029
  • Spohr L, Luduvico KP, Soares MSP, et al. Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide. Nutr Neurosci. 2022;25(4):857-870. doi:10.1080/1028415X.2020.1819104
  • Berg BM, Godbout JP, Chen J, Kelley KW, Johnson RW. Alpha-tocopherol and selenium facilitate recovery from lipopolysaccharide-induced sickness in aged mice. J Nutr. 2005;135(5):1157-1163. doi:10. 1093/jn/135.5.1157
  • Altar CA, Cai N, Bliven T, et al. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature. 1997;389(6653):856-860. doi:10.1038/39885
  • Du J, An J, Wei N, Guan T, Pritchard KA Jr, Shi Y. Increased resistance to LPS-induced myocardial dysfunction in the Brown Norway rats versus Dahl S rats: roles of inflammatory cytokines and nuclear factor kappa B pathway. Shock. 2010;33(3):332-336. doi:10.1097/SHK.0b013e3181b7819e
  • Koc F, Tekeli MY, Kanbur M, Karayigit MÖ, Liman BC. The effects of chrysin on lipopolysaccharide-induced sepsis in rats. J Food Biochem. 2020;44(9):e13359. doi:10.1111/jfbc.13359
  • Reyes EP, Abarzúa S, Martin A, Rodríguez J, Cortés PP, Fernández R. LPS-induced c-Fos activation in NTS neurons and plasmatic cortisol increases in septic rats are suppressed by bilateral carotid chemodenervation. Adv Exp Med Biol. 2012;758:185-190. doi:10.1007/ 978-94-007-4584-1_26
  • Ribeiro DE, Maiolini VM, Soncini R, et al. Inhibition of nitric oxide synthase accentuates endotoxin-induced sickness behavior in mice. Pharmacol Biochem Behav. 2013;103(3):535-540. doi:10.1016/j.pbb.2012. 09.022
  • Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019;10(2):128. doi:10.1038/s41419-019-1413-8
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Details

Primary Language English
Subjects Physiopathology
Journal Section Research Article
Authors

Hasan Çalışkan 0000-0002-3729-1863

Submission Date May 5, 2025
Acceptance Date June 30, 2025
Publication Date July 30, 2025
DOI https://doi.org/10.32322/jhsm.1691744
IZ https://izlik.org/JA58PS52UL
Published in Issue Year 2025 Volume: 8 Issue: 4

Cite

AMA 1.Çalışkan H. Turning preferences in the corner turning test and the status of proinflammatory cytokines in the right-left brain hemispheres in the lipopolysaccharide-induced neuroinflammation model. J Health Sci Med / JHSM. 2025;8(4):640-645. doi:10.32322/jhsm.1691744

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