Top

25-03-2024 | Anxiety

Effects of lipopolysaccharide administration at different postnatal periods on behavioral and biochemical assessments in Wistar rats

Authors: Hajar Benmhammed, Mouloud Lamtai, Abdelhalem Mesfioui, Abdeljabbar Nassiri, Samira Mouden, Samir Bikri, Aboubaker El Hessni

Published in: Neuroscience and Behavioral Physiology

Abstract

Rodent model systems using lipopolysaccharide (LPS) administration have been developed to examine the effect of postnatal inflammation on neuropsychiatric behaviors. In this study, we investigated the effect of 250 μg/kg of LPS administration in male and female Wistar rats at three different postnatal periods. Rats were divided into four groups: a control group which received an intraperitoneal (IP) injection of phosphate buffer saline (PBS) on postnatal day 1 and three experimental groups which received an IP injection of LPS (250 μg/kg) at three different postnatal periods: day 1, day 3 and day 5. Each group consisted of 12 rats and had an equal gender distribution. At three months, rats were subjected to neurobehavioral assessments and biochemical oxidative and inflammatory assays. As a trend, LPS administration generates uniform anxiogenic behaviors, a depressive response, and increased central oxidative and inflammatory stress across all groups as compared to controls. Males receiving an LPS injection at postnatal days 1 and 3 and females receiving it at days 3 and 5 displayed more anxiogenic and depressive responses than their gender counterparts. Females had higher biomarker levels, with results being more pronounced in the group receiving injection on day 3. Postnatal LPS induces emotional disturbances along with oxidative stress and inflammation in brain tissues. Response to LPS injection seems to be gender-dependent and modulated by several variables, including its time of administration. Further investigations that take into consideration these variables, among others, are needed.

Bale TL, Epperson CN (2015) Sex differences and stress across the lifespan. Nat Neurosci 18(10):1413–1420. https://doi.org/10.1038/nn.4112CrossRefPubMedPubMedCentral

Barichello T, Dos Santos I, Savi GD, Florentino AF, Silvestre C, Comim CM, Feier G, Sachs D, Teixeira MM, Teixeira AL, Quevedo J (2009) Tumor necrosis factor alpha (TNF-α) levels in the brain and cerebrospinal fluid after meningitis induced by Streptococcus pneumoniae. Neuroscience Letters 467(3):217–219. https://doi.org/10.1016/j.neulet.2009.10.039CrossRefPubMed

Benmhammed H, El Hayek S, Nassiri A, Bousalham R, Mesfioui A, Ouichou A, El Hessni A (2019) Effects of lipopolysaccharide administration and maternal deprivation on anxiety and depressive symptoms in male and female Wistar rats: Neurobehavioral and biochemical assessments. Behavioural Brain Research 362:46–55. https://doi.org/10.1016/j.bbr.2019.01.005CrossRefPubMed

Bennet L, Gunn AJ (2006) The Fetal Origins of Adult Mental Illness. In: Wintour EM, Owens JA (eds) Early Life Origins of Health and Disease. Springer US, Boston, MA, pp 204–218CrossRef

Benson S, Brinkhoff A, Lueg L, Roderigo T, Kribben A, Wilde B, Witzke O, Engler H, Schedlowski M, Elsenbruch S (2017) Effects of acute systemic inflammation on the interplay between sad mood and affective cognition. Transl Psychiatry 7(12):1281. https://doi.org/10.1038/s41398-017-0043-0CrossRefPubMedPubMedCentral

Berkiks I, Benmhammed H, Mesfioui A, Ouichou A, El Hasnaoui A, Mouden S, Touil T, Bahbiti Y, Nakache R, El Hessni A (2018a) Postnatal melatonin treatment protects against affective disorders induced by early-life immune stimulation by reducing the microglia cell activation and oxidative stress. International Journal of Neuroscience 128(6):495–504. https://doi.org/10.1080/00207454.2017.1398156CrossRefPubMed

Berkiks I, Boulbaroud S, Garcia-Segura LM, Mesfioui A, Ouichou A, Mouden S, Benmhammed H, El Hasnaoui A, Nakache R, Bahbiti Y, El Hessni A (2018b) Thymelaea lythroides extract attenuates microglial activation and depressive-like behavior in LPS-induced inflammation in adult male rats. Biomedicine & Pharmacotherapy 99:655–663. https://doi.org/10.1016/j.biopha.2018.01.125CrossRef

Berkiks I, Garcia-Segura LM, Nassiri A, Mesfioui A, Ouichou A, Boulbaroud S, Bahbiti Y, Lopez-Rodriguez AB, Hasnaoui E, El Hessni A (2019) The sex differences of the behavior response to early Life immune stimulation: Microglia and astrocytes involvement. Physiology & Behavior 199:386–394. https://doi.org/10.1016/j.physbeh.2018.11.037CrossRef

Bernardi MM, Teixeira LP, Ligeiro-de-Oliveira AP, Tavares-de-Lima W, Palermo-Neto J, Kirsten TB (2014) Neonatal lipopolysaccharide exposure induces sexually dimorphic sickness behavior in adult rats. Psychology & Neuroscience 7(2):113–123. https://doi.org/10.3922/j.psns.2014.007CrossRef

10.

Bilbo SD (2009) Early-life programming of later-life brain and behavior: a critical role for the immune system. Front Behav Neurosci 3. https://doi.org/10.3389/neuro.08.014.2009

11.

Bland ST, Beckley JT, Young S, Tsang V, Watkins LR, Maier SF, Bilbo SD (2010) Enduring consequences of early-life infection on glial and neural cell genesis within cognitive regions of the brain. Brain, Behavior, and Immunity 24(3):329–338. https://doi.org/10.1016/j.bbi.2009.09.012CrossRefPubMed

12.

Bourin M, Hascoët M (2003) The mouse light/dark box test. European Journal of Pharmacology 463(1–3):55–65. https://doi.org/10.1016/S0014-2999(03)01274-3CrossRefPubMed

13.

Brown P (2007) Abnormal oscillatory synchronisation in the motor system leads to impaired movement. Current Opinion in Neurobiology 17(6):656–664. https://doi.org/10.1016/j.conb.2007.12.001CrossRefPubMed

14.

Brunton PJ (2015) Programming the Brain and Behaviour by Early-Life Stress: A Focus on Neuroactive Steroids. J Neuroendocrinol 27(6):468–480. https://doi.org/10.1111/jne.12265CrossRefPubMed

15.

Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti J-F, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 56(7):1761–1772. https://doi.org/10.2337/db06-1491CrossRefPubMed

16.

Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK (1992) Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol 149(8):2736–2741CrossRefPubMed

17.

Claypoole LD, Zimmerberg B, Williamson LL (2017) Neonatal lipopolysaccharide treatment alters hippocampal neuroinflammation, microglia morphology and anxiety-like behavior in rats selectively bred for an infantile trait. Brain, Behavior, and Immunity 59:135–146. https://doi.org/10.1016/j.bbi.2016.08.017CrossRefPubMed

18.

Csiszar A, Wang M, Lakatta EG, Ungvari Z (2008) Inflammation and endothelial dysfunction during aging: role of NF-κB. Journal of Applied Physiology 105(4):1333–1341. https://doi.org/10.1152/japplphysiol.90470.2008CrossRefPubMedPubMedCentral

19.

Custódio CS, Mello BSF, Filho AJMC, De Carvalho Lima CN, Cordeiro RC, Miyajima F, Réus GZ, Vasconcelos SMM, Barichello T, Quevedo J, De Oliveira AC, De Lucena DF, Macedo DS (2017) Neonatal Immune Challenge with Lipopolysaccharide Triggers Long-lasting Sex- and Age-related Behavioral and Immune/Neurotrophic Alterations in Mice: Relevance to Autism Spectrum Disorders. Mol Neurobiol. https://doi.org/10.1007/s12035-017-0616-1CrossRefPubMed

20.

Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56. https://doi.org/10.1038/nrn2297CrossRefPubMedPubMedCentral

21.

Depino AM (2015) Early prenatal exposure to LPS results in anxiety- and depression-related behaviors in adulthood. Neuroscience 299:56–65. https://doi.org/10.1016/j.neuroscience.2015.04.065CrossRefPubMed

22.

Doenni VM, Song CM, Hill MN, Pittman QJ (2017) Early-life inflammation with LPS delays fear extinction in adult rodents. Brain, Behavior, and Immunity 63:176–185. https://doi.org/10.1016/j.bbi.2016.11.022CrossRefPubMed

23.

Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431. https://doi.org/10.1016/0076-6879(90)86135-iCrossRefPubMed

24.

El Brouzi MY, Lamtai M, Zghari O, Ouakki S, Azizoun I, El Hessni A, Mesfioui A, Ouichou A (2021) Intrahippocampal Effects of Nickel Injection on the Affective and Cognitive Response in Wistar Rat: Potential Role of Oxidative Stress. Biol Trace Elem Res 199(9):3382–3392. https://doi.org/10.1007/s12011-020-02457-5CrossRefPubMed

25.

Engler H, Benson S, Wegner A, Spreitzer I, Schedlowski M, Elsenbruch S (2016) Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms. Brain, Behavior, and Immunity 52:18–26. https://doi.org/10.1016/j.bbi.2015.08.013CrossRefPubMed

26.

Fan L-W, Tien L-T, Lin RCS, Simpson KL, Rhodes PG, Cai Z (2011) Neonatal exposure to lipopolysaccharide enhances vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life. Neurobiology of Disease 44(3):304–316. https://doi.org/10.1016/j.nbd.2011.07.011CrossRefPubMedPubMedCentral

27.

Fish EN (2008) The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol 8(9):737–744. https://doi.org/10.1038/nri2394CrossRefPubMedPubMedCentral

28.

Freitas RM, Sousa FCF, Vasconcelos SMM, Viana GSB, Fonteles MMF (2004) Pilocarpine-induced status epilepticus in rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex. Pharmacology Biochemistry and Behavior 78(2):327–332. https://doi.org/10.1016/j.pbb.2004.04.004CrossRefPubMed

29.

Garcia AMB, Cardenas FP, Morato S (2005) Effect of different illumination levels on rat behavior in the elevated plus-maze. Physiology & Behavior 85(3):265–270. https://doi.org/10.1016/j.physbeh.2005.04.007CrossRef

30.

Harman D (1956) Aging: A Theory Based on Free Radical and Radiation Chemistry. Journal of Gerontology 11(3):298–300. https://doi.org/10.1093/geronj/11.3.298CrossRefPubMed

31.

Harvey L, Boksa P (2012) Prenatal and postnatal animal models of immune activation: Relevance to a range of neurodevelopmental disorders. Devel Neurobio 72(10):1335–1348. https://doi.org/10.1002/dneu.22043CrossRef

32.

Hostinar CE (2015) Recent developments in the study of social relationships, stress responses, and physical health. Current Opinion in Psychology 5:90–95. https://doi.org/10.1016/j.copsyc.2015.05.004CrossRefPubMedPubMedCentral

33.

Kokras N, Antoniou K, Mikail HG, Kafetzopoulos V, Papadopoulou-Daifoti Z, Dalla C (2015) Forced swim test: What about females? Neuropharmacology 99:408–421. https://doi.org/10.1016/j.neuropharm.2015.03.016CrossRefPubMed

34.

Lamtai M, Ouakki S, Zghari O, Hamzaoui AE, Benmhammed H, Azirar S, Hessni AE, Mesfioui A, Ouichou A (2020) Neuroprotective effect of melatonin on nickel-induced affective and cognitive disorders and oxidative damage in rats. Environ Anal Health Toxicol 35(4):e2020025. https://doi.org/10.5620/eaht.2020025CrossRefPubMedPubMedCentral

35.

Liao J-C, Tsai J-C, Liu C-Y, Huang H-C, Wu L-Y, Peng W-H (2013) Antidepressant-like activity of turmerone in behavioral despair tests in mice. BMC Complement Altern Med 13(1):299. https://doi.org/10.1186/1472-6882-13-299CrossRefPubMedPubMedCentral

36.

Linthorst AC, Reul JM (1998) Brain neurotransmission during peripheral inflammation. Ann N Y Acad Sci 840:139–152. https://doi.org/10.1111/j.1749-6632.1998.tb09558.xCrossRefPubMed

37.

Lu Y-C, Yeh W-C, Ohashi PS (2008) LPS/TLR4 signal transduction pathway. Cytokine 42(2):145–151. https://doi.org/10.1016/j.cyto.2008.01.006CrossRefPubMed

38.

Ma M, Ren Q, Yang C, Zhang J, Yao W, Dong C, Ohgi Y, Futamura T, Hashimoto K (2017) Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation. Psychopharmacology 234(4):525–533. https://doi.org/10.1007/s00213-016-4483-7CrossRefPubMed

39.

Majidi-Zolbanin J, Azarfarin M, Samadi H, Enayati M, Salari A-A (2013) Adolescent fluoxetine treatment decreases the effects of neonatal immune activation on anxiety-like behavior in mice. Behavioural Brain Research 250:123–132. https://doi.org/10.1016/j.bbr.2013.05.003CrossRefPubMed

40.

Moieni M, Irwin MR, Jevtic I, Olmstead R, Breen EC, Eisenberger NI (2015) Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression. Neuropsychopharmacol 40(7):1709–1716. https://doi.org/10.1038/npp.2015.17CrossRef

41.

Naïla N, Makthar W, Lamtai M, Zghari O, Aboubaker EH, Abdelhalem M, Ali O (2021) Effect of intra-hippocampal lead injection on affective and cognitive disorders in male WISTAR rats: Possible involvement of oxidative stress. E3S Web Conf 319:02017. https://doi.org/10.1051/e3sconf/202131902017

42.

O’Connor M-F, Bower JE, Cho HJ, Creswell JD, Dimitrov S, Hamby ME, Hoyt MA, Martin JL, Robles TF, Sloan EK, Thomas KS, Irwin MR (2009) To assess, to control, to exclude: Effects of biobehavioral factors on circulating inflammatory markers. Brain, Behavior, and Immunity 23(7):887–897. https://doi.org/10.1016/j.bbi.2009.04.005CrossRefPubMedPubMedCentral

43.

O’Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho A-M, Quigley EMM, Cryan JF, Dinan TG (2009) Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses. Biological Psychiatry 65(3):263–267. https://doi.org/10.1016/j.biopsych.2008.06.026CrossRefPubMed

44.

Pitossi F, del Rey A, Kabiersch A, Besedovsky H (1997) Induction of cytokine transcripts in the central nervous system and pituitary following peripheral administration of endotoxin to mice. J Neurosci Res 48(4):287–298. https://doi.org/10.1002/(sici)1097-4547(19970515)48:4<287::aid-jnr1>3.0.co;2-7CrossRefPubMed

45.

Pitychoutis PM, Papadopoulou-Daifoti Z (2010) Of depression and immunity: does sex matter? Int J Neuropsychopharm 13(05):675–689. https://doi.org/10.1017/S1461145710000465CrossRef

46.

Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: A new model sensitive to antidepressant treatments. European Journal of Pharmacology 47(4):379–391. https://doi.org/10.1016/0014-2999(78)90118-8CrossRefPubMed

47.

Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. European Journal of Pharmacology 463(1–3):3–33. https://doi.org/10.1016/S0014-2999(03)01272-XCrossRefPubMed

48.

Sominsky L, Walker AK, Ong LK, Tynan RJ, Walker FR, Hodgson DM (2012) Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic. Behavioural Brain Research 226(1):351–356. https://doi.org/10.1016/j.bbr.2011.08.038CrossRefPubMed

49.

Spatz Widom C, DuMont K, Czaja SJ (2007) A Prospective Investigation of Major Depressive Disorder and Comorbidity in Abused and Neglected Children Grown Up. Arch Gen Psychiatry 64(1):49. https://doi.org/10.1001/archpsyc.64.1.49CrossRef

50.

Spencer SJ, Heida JG, Pittman QJ (2005) Early life immune challenge—effects on behavioural indices of adult rat fear and anxiety. Behavioural Brain Research 164(2):231–238. https://doi.org/10.1016/j.bbr.2005.06.032CrossRefPubMed

51.

Sramek JJ, Murphy MF, Cutler NR (2016) Sex differences in the psychopharmacological treatment of depression. Dialogues Clin Neurosci 18(4):447–457. https://doi.org/10.31887/DCNS.2016.18.4/ncutler

52.

Tishkina A, Stepanichev M, Kudryashova I, Freiman S, Onufriev M, Lazareva N, Gulyaeva N (2016) Neonatal proinflammatory challenge in male Wistar rats: Effects on behavior, synaptic plasticity, and adrenocortical stress response. Behavioural Brain Research 304:1–10. https://doi.org/10.1016/j.bbr.2016.02.001CrossRefPubMed

53.

Walker AK, Nakamura T, Byrne RJ, Naicker S, Tynan RJ, Hunter M, Hodgson DM (2009) Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behaviour and blunted corticosterone responses: Implications for the double-hit hypothesis. Psychoneuroendocrinology 34(10):1515–1525. https://doi.org/10.1016/j.psyneuen.2009.05.010CrossRefPubMed

54.

Walker AK, Nakamura T, Hodgson DM (2010) Neonatal lipopolysaccharide exposure alters central cytokine responses to stress in adulthood in Wistar rats. Stress 13(6):506–515. https://doi.org/10.3109/10253890.2010.489977CrossRefPubMed

55.

Walker FR, March J, Hodgson DM (2004) Endotoxin exposure in early life alters the development of anxiety-like behaviour in the Fischer 344 rat. Behavioural Brain Research 154(1):63–69. https://doi.org/10.1016/j.bbr.2004.01.019CrossRefPubMed

56.

Wang K-C, Fan L-W, Kaizaki A, Pang Y, Cai Z, Tien L-T (2013) Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats. Neuroscience 234:146–157. https://doi.org/10.1016/j.neuroscience.2012.12.049CrossRefPubMed

57.

Watson RE, DeSesso JM, Hurtt ME, Cappon GD (2006) Postnatal growth and morphological development of the brain: a species comparison. Birth Defect Res B 77(5):471–484. https://doi.org/10.1002/bdrb.20090CrossRef

58.

Zghari O, Azirar S, Lamtai M, El Hessni A, Ouichou A, Mesfioui A (2023) Melatonin counteracts aluminum-induced affective and cognitive disorders and oxidative damage in male wistar rats. Neurosci Behav Physi 53(6):917–928. https://doi.org/10.1007/s11055-023-01465-xCrossRef

59.

Zhan X, Stamova B, Jin L-W, DeCarli C, Phinney B, Sharp FR (2016) Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology 87(22):2324–2332. https://doi.org/10.1212/WNL.0000000000003391CrossRefPubMedPubMedCentral

60.

Zhang X-Y, Cao J-B, Zhang L-M, Li Y-F, Mi W-D (2015) Deferoxamine attenuates lipopolysaccharide-induced neuroinflammation and memory impairment in mice. J Neuroinflammation 12(1):20. https://doi.org/10.1186/s12974-015-0238-3CrossRefPubMedPubMedCentral

Title: Effects of lipopolysaccharide administration at different postnatal periods on behavioral and biochemical assessments in Wistar rats
Authors: Hajar Benmhammed
Mouloud Lamtai
Abdelhalem Mesfioui
Abdeljabbar Nassiri
Samira Mouden
Samir Bikri
Aboubaker El Hessni
Publication date: 25-03-2024
Publisher: Springer International Publishing
Keywords: Anxiety
Mood Disorders
Affective Disorder
Published in: Neuroscience and Behavioral Physiology
Print ISSN: 0097-0549
Electronic ISSN: 1573-899X
DOI: https://doi.org/10.1007/s11055-024-01584-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of lipopolysaccharide administration at different postnatal periods on behavioral and biochemical assessments in Wistar rats

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content