Background: Prenatal maternal lipopolysaccharide (LPS) exposure causes behavioral deficits in adulthood. LPS-exposure cause oxidative damage and cytokines production. In contrast, astaxanthin (Ast) is a carotenoid antioxidant that shows protective effects through its antioxidant capacity.
Objectives: This study investigates the effect of prenatal treatment with astaxanthin on the behavioral deficit (including sexual, depressive, and anxiety-like behavior) caused by prenatal maternal LPS in adult male offspring.
Methods: Pregnant mice were randomly divided into 4 groups: (1) control, (2) LPS: injecting with LPS (20 µg/kg, sc.) on gestation day 11, (3) Ast: receiving astaxanthin (4 mg/kg for 3 days, i.p.) on 11 - 13th gestation day, (4) LPS+Ast: injecting with LPS (20 µg/kg, sc.) on gestation day 11 and receiving astaxanthin (4 mg/kg for 3 days, i.p.) on 11 - 13th gestation day. Then in each group, 23 day old male offspring (3 and 12 male children from each mother and group, respectively) were separated from mothers and then the sexual, depressive and anxiety-like behaviors were examined in adult male mice.
Results: Findings showed that prenatal LPS-exposed mice had more anxiety and spent less time in open arms of the elevated plus-maze test (P < 0.05). In addition, it decreased sexual behaviors, the amount of which was significant in the number of sniffing, following behaviors (P < 0.01). Also, there was no significant difference between different groups in the forced swimming test (P < 0.05). On the other hand, prenatal treatment with astaxanthin significantly elevated the percentage of open arm time and open arm entry, without altering in locomotor activity (P < 0.05). Also, it significantly increased sexual behavior in Ast and LPS+Ast groups (P < 0.01).
Conclusions: The obtained results suggest that prenatal maternal exposure to LPS impaired several aspects of male sexual behavior and resulted in behavioral deficits in adulthood, while astaxanthin has an antianxiety effect and improves the deficits of sexual behavior presumably via its antioxidant property.
- Bernardi MM, Kirsten TB, Matsuoka SM, Teodorov E, Habr SF, Penteado SH, et al. Prenatal lipopolysaccharide exposure affects maternal behavior and male offspring sexual behavior in adulthood. Neuroimmunomodulation. 2010;17(1):47-55. doi: 10.1159/000243085. [PubMed: 19816057].
- Yoon HJ, Moon ME, Park HS, Im SY, Kim YH. Chitosan oligosaccharide (COS) inhibits LPS-induced inflammatory effects in RAW 264.7 macrophage cells. Biochem Biophys Res Commun. 2007;358(3):954-9. doi: 10.1016/j.bbrc.2007.05.042. [PubMed: 17512902].
- Boksa P. Effects of prenatal infection on brain development and behavior: A review of findings from animal models. Brain Behav Immun. 2010;24(6):881-97. doi: 10.1016/j.bbi.2010.03.005. [PubMed: 20230889].
- Romero E, Guaza C, Castellano B, Borrell J. Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: Implications for the etiopathology of schizophrenia. Mol Psychiatry. 2010;15(4):372-83. doi: 10.1038/mp.2008.44. [PubMed: 18414405].
- Wang H, Yang LL, Hu YF, Wang BW, Huang YY, Zhang C, et al. Maternal LPS exposure during pregnancy impairs testicular development, steroidogenesis and spermatogenesis in male offspring. PLoS One. 2014;9(9). e106786. doi: 10.1371/journal.pone.0106786. [PubMed: 25255222]. [PubMed Central: PMC4177809].
- Al-Amin MM, Sultana R, Sultana S, Rahman MM, Reza HM. Astaxanthin ameliorates prenatal LPS-exposed behavioral deficits and oxidative stress in adult offspring. BMC Neurosci. 2016;17:11. doi: 10.1186/s12868-016-0245-z. [PubMed: 26856812]. [PubMed Central: PMC4746928].
- Naguib YM. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000;48(4):1150-4. doi: 10.1021/jf991106k. [PubMed: 10775364].
- Yamashita E. Astaxanthin as a medical food. Funct Food Health Dis. 2013;3(7):254. doi: 10.31989/ffhd.v3i7.49.
- Cui L, Xu F, Wang M, Li L, Qiao T, Cui H, et al. Dietary natural astaxanthin at an early stage inhibits N-nitrosomethylbenzylamine-induced esophageal cancer oxidative stress and inflammation via downregulation of NFkappaB and COX2 in F344 rats. Onco Targets Ther. 2019;12:5087-96. doi: 10.2147/OTT.S197044. [PubMed: 31308688]. [PubMed Central: PMC6612988].
- Zhang XS, Zhang X, Wu Q, Li W, Wang CX, Xie GB, et al. Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage. J Surg Res. 2014;192(1):206-13. doi: 10.1016/j.jss.2014.05.029. [PubMed: 24948541].
- Evans NP, Bellingham M, Robinson JE. Prenatal programming of neuroendocrine reproductive function. Theriogenology. 2016;86(1):340-8. doi: 10.1016/j.theriogenology.2016.04.047. [PubMed: 27142489].
- Herbst LS, Gaigher T, Siqueira AA, Joca SRL, Sampaio KN, Beijamini V. New evidence for refinement of anesthetic choice in procedures preceding the forced swimming test and the elevated plus-maze. Behav Brain Res. 2019;368:111897. doi: 10.1016/j.bbr.2019.04.011. [PubMed: 30978407].
- Solati J, Hajikhani R, Toodeh Zaeim R. Effects of cypermethrin on sexual behaviour and plasma concentrations of pituitary-gonadal hormones. Int J Fertil Steril. 2010;4(1).
- Zavvari F, Karimzadeh F. A methodological review of development and assessment of behavioral models of depression in rats. Neurosci J Shefaye Khatam. 2015;3(4):151-60. doi: 10.18869/acadpub.shefa.3.4.151.
- Hava G, Vered L, Yael M, Mordechai H, Mahoud H. Alterations in behavior in adult offspring mice following maternal inflammation during pregnancy. Dev Psychobiol. 2006;48(2):162-8. doi: 10.1002/dev.20116. [PubMed: 16489598].
- Nishioka Y, Oyagi A, Tsuruma K, Shimazawa M, Ishibashi T, Hara H. The antianxiety-like effect of astaxanthin extracted from Paracoccus carotinifaciens. Biofactors. 2011;37(1):25-30. doi: 10.1002/biof.130. [PubMed: 21328624].
- Al-Amin MM, Rahman MM, Khan FR, Zaman F, Mahmud Reza H. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism. Behav Brain Res. 2015;286:112-21. doi: 10.1016/j.bbr.2015.02.041. [PubMed: 25732953].
- Ying CJ, Zhang F, Zhou XY, Hu XT, Chen J, Wen XR, et al. Anti-inflammatory effect of astaxanthin on the sickness behavior induced by diabetes mellitus. Cell Mol Neurobiol. 2015;35(7):1027-37. doi: 10.1007/s10571-015-0197-3. [PubMed: 25971983].
- Wijkstra S, Valkhof N, Koolhaas JM, Schuiling GA. Endotoxin treatment of pregnant rats affects sexual behavior of the male offspring. Physiol Behav. 1991;49(3):647-9. doi: 10.1016/0031-9384(91)90294-x.