[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: Volume 31, Issue 4 (WINTER 2021) ::
MEDICAL SCIENCES 2021, 31(4): 397-405 Back to browse issues page
Study on the effect of acetyl L-carnitine on cognitive and cellular disorders resulting from lipopolysaccharide-induced inflammation in male rats: emphasis on AKT / mTOR cell pathways and inflammation in the hippocampus
Nida Jamali-Raeufy 1, Motahareh Zeinivand2 , Fahimeh Alizadeh3 , Soraya Mehrabi4
1- Associate Professor, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran , jamali.n@iums.ac.ir
2- Assistant Professor, Department of Physiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
3- MSc, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4- Assistant Professor, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Abstract:   (913 Views)
Background: The brain in exposure to irritating factors may lead to production of some chemical factors and proinflammatory cytokines and neuroinflammation. Over time, the chronic neuroinflammation will cause some cognitive disorders and neurodegenerative diseases. The present study studied the effect of acetyl L -carnitine on cognitive and cellular disorders derived from lipopolysaccharide (LPS)- induced inflammation, with emphasis on cellular pathways in the hippocampus of male rat.
Materials and methods: In this study, we used LPS with dose of 500 μg/kg of animal’s weight regarding to the previous studies. Acetyl L carnitine was prescribed with three doses of 30, 60 and 100 mg/kg among rats received LPS. Passive avoidance behavior was used to assess learning and memory, and biochemical and molecular methods were used for mTOR, p-AKT, and inflammatory factors.
Results: Acetyl L carnitine improved passive avoidance memory as well as working memory in a dose-dependent manner. It also prevented the death of hippocampal neurons by inhibiting neuroinflammation by reducing the expression of IL-6 and IL-1B and increasing the levels of mTOR and AKT-p.
Conclusion: The present study showed that acetyl L-carnitine can reduce the destructive effects of lipopolysaccharide, which appears to be through increased levels of mTOR and AKT.
Keywords: Neuroinflammation, Lipopolysaccharide (LPS), Memory, Acetyl L carnitine
Full-Text [PDF 400 kb]   (276 Downloads)    
Semi-pilot: Experimental | Subject: Brain and Nerves System
Received: 2021/05/15 | Accepted: 2021/07/5
1. Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science 2016;353:777-83. [DOI:10.1126/science.aag2590]
2. Gavilán MP, Revilla E, Pintado C, Castaño A, Vizuete ML, Moreno‐González I, et al. Molecular and cellular characterization of the age‐related neuroinflammatory processes occurring in normal rat hippocampus: potential relation with the loss of somatostatin GABAergic neurons. J Neurochem 2007;103:984-96. [DOI:10.1111/j.1471-4159.2007.04787.x]
3. Poustchi F, Amani H, Ahmadian Z, Niknezhad SV, Mehrabi S, Santos HA, et al. Combination therapy of killing diseases by injectable hydrogels: from concept to medical applications. Adv Healthc Mater 2021;10:2001571. [DOI:10.1002/adhm.202001571]
4. Pintado C, Gavilán MP, Gavilán E, García-Cuervo L, Gutiérrez A, Vitorica J, et al. Lipopolysaccharide-induced neuroinflammation leads to the accumulation of ubiquitinated proteins and increases susceptibility to neurodegeneration induced by proteasome inhibition in rat hippocampus. J neuroinflammation 2012;9:1-10. [DOI:10.1186/1742-2094-9-87]
5. Cunningham C. Microglia and neurodegeneration: the role of systemic inflammation. Glia 2013;61:71-90. [DOI:10.1002/glia.22350]
6. Gahtan E, Overmier JB. Inflammatory pathogenesis in Alzheimer's disease: biological mechanisms and cognitive sequeli. Neurosci Biobehav Rev 1999;23:615-33. [DOI:10.1016/S0149-7634(98)00058-X]
7. Kim J, Kundu M, Viollet B, Guan K-L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-41. [DOI:10.1038/ncb2152]
8. Pillich RT, Scarsella G, Risuleo G. Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture. Exp Cell Res 2005;306:1-8. [DOI:10.1016/j.yexcr.2005.01.019]
9. Hall ED. Antioxidant therapies for acute spinal cord injury. Neurotherapeutics 2011;8:152-67. [DOI:10.1007/s13311-011-0026-4]
10. Karalija A, Novikova LN, Kingham PJ, Wiberg M, Novikov LN. The effects of N-acetyl-cysteine and acetyl-L-carnitine on neural survival, neuroinflammation and regeneration following spinal cord injury. Neuroscience 2014; 269:143-51. [DOI:10.1016/j.neuroscience.2014.03.042]
11. Bagyinszky E, Van Giau V, Shim K, Suk K, An SSA, Kim S. Role of inflammatory molecules in the Alzheimer's disease progression and diagnosis. J Neurol Sci 2017;376:242-54. [DOI:10.1016/j.jns.2017.03.031]
12. Rocha EM, De Miranda B, Sanders LH. Alpha-synuclein: pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease. Neurobiol Dis 2018;109:249-57. [DOI:10.1016/j.nbd.2017.04.004]
13. Koudriavtseva T, Mainero C. Neuroinflammation, neurodegeneration and regeneration in multiple sclerosis: intercorrelated manifestations of the immune response. Neural Regen Res 2016;11:1727. [DOI:10.4103/1673-5374.194804]
14. Hsing C-H, Hung S-K, Chen Y-C, Wei T-S, Sun D-P, Wang J-J, et al. Histone deacetylase inhibitor trichostatin a ameliorated endotoxin-induced neuroinflammation and cognitive dysfunction. Mediat Inflamm 2015;2015:163140. [DOI:10.1155/2015/163140]
15. Anaeigoudari A, Soukhtanloo M, Reisi P, Beheshti F, Hosseini M. Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat. Life Sci 2016;158:22-30. [DOI:10.1016/j.lfs.2016.06.019]
16. Song X, Zhou B, Zhang P, Lei D, Wang Y, Yao G, et al. Protective effect of silibinin on learning and memory impairment in LPS-treated rats via ROS-BDNF-TrkB pathway. Neurochem Res 2016;41:1662-72. [DOI:10.1007/s11064-016-1881-5]
17. Sun J, Zhang S, Zhang X, Zhang X, Dong H, Qian Y. IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. J Neuroinflammation 2015;12:1-12 [DOI:10.1186/s12974-015-0394-5]
18. Khalili M, Alavi M, Esmaeil-Jamaat E, Baluchnejadmojarad T, Roghani M. Trigonelline mitigates lipopolysaccharide-induced learning and memory impairment in the rat due to its anti-oxidative and anti-inflammatory effect. Int Immunopharmacol 2018;61:355-62. [DOI:10.1016/j.intimp.2018.06.019]
19. Czerniawski J, Miyashita T, Lewandowski G, Guzowski JF. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation. Brain Behav Immun 2015;44:159-66. [DOI:10.1016/j.bbi.2014.09.014]
20. Zarezadeh M, Baluchnejadmojarad T, Kiasalari Z, Afshin-Majd S, Roghani M. Garlic active constituent s-allyl cysteine protects against lipopolysaccharide-induced cognitive deficits in the rat: possible involved mechanisms. Eur J Pharmacol 2017;795:13-21. [DOI:10.1016/j.ejphar.2016.11.051]
21. Zhu Z, Yang C, Iyaswamy A, Krishnamoorthi S, Sreenivasmurthy SG, Liu J, et al. Balancing mtor signaling and autophagy in the treatment of parkinson's disease. Int J Mol Sci 2019;20:728. [DOI:10.3390/ijms20030728]
22. Domanskyi A, Geißler C, Vinnikov IA, Alter H, Schober A, Vogt MA, et al. Pten ablation in adult dopaminergic neurons is neuroprotective in Parkinson's disease models. FASEB J 2011;25:2898-910. [DOI:10.1096/fj.11-181958]
23. Tan C-C, Yu J-T, Tan M-S, Jiang T, Zhu X-C, Tan L. Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Neurobiol Aging 2014;35:941-57. [DOI:10.1016/j.neurobiolaging.2013.11.019]
24. Su P, Zhang J, Wang D, Zhao F, Cao Z, Aschner M, et al. The role of autophagy in modulation of neuroinflammation in microglia. Neuroscience 2016;319:155-67. [DOI:10.1016/j.neuroscience.2016.01.035]
25. Zhang S, Xue Z-F, Huang L-P, Fang R-M, He Y-P, Li L, et al. Dynamic expressions of Beclin 1 and tyrosine hydroxylase in different areas of 6-hydroxydopamine-induced Parkinsonian rats. Cell Mol Neurobiol 2013;33:973-81. [DOI:10.1007/s10571-013-9964-1]
26. Weis S, Toniazzo A, Ander B, Zhan X, Careaga M, Ashwood P, et al. Autophagy in the brain of neonates following hypoxia-ischemia shows sex-and region-specific effects. Neuroscience 2014;256:201-9. [DOI:10.1016/j.neuroscience.2013.10.046]
27. Pérez‐Rodríguez D, Anuncibay‐Soto B, Llorente IL, Pérez‐García CC, Fernández‐López A. Hippocampus and cerebral cortex present a different autophagic response after oxygen and glucose deprivation in an ex vivo rat brain slice model. Neuropathol Appl Neurobiol 2015;41:e68-e79. [DOI:10.1111/nan.12152]
28. François A, Terro F, Quellard N, Fernandez B, Chassaing D, Janet T, et al. Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice. Mol Brain 2014;7:56. [DOI:10.1186/s13041-014-0056-z]
29. Bales KR, Du Y, Dodel RC, Yan G-M, Hamilton-Byrd E, Paul SM. The NF-κB/Rel family of proteins mediates Aβ-induced neurotoxicity and glial activation. Brain Res Mol 1998;57:63-72. [DOI:10.1016/S0169-328X(98)00066-7]
30. Hedde JR, Hanks AN, Schmidt CJ, Hughes ZA. The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the effects of lipopolysaccharide in human cells and rodent models of peripheral and CNS inflammation. Brain Behav Immun 2017;64:285-95. [DOI:10.1016/j.bbi.2017.04.015]
31. Afshin-Majd S, Bashiri K, Kiasalari Z, Baluchnejadmojarad T, Sedaghat R, Roghani M. Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson's disease in the rat. Biomed Pharmacother 2017;89:1-9. [DOI:10.1016/j.biopha.2017.02.007]
32. Ownby RL. Neuroinflammation and cognitive aging. Curr Psychiatry Rep 2010;12:39-45 [DOI:10.1007/s11920-009-0082-1]
33. Okun E, Barak B, Saada-Madar R, Rothman SM, Griffioen KJ, Roberts N, et al. Evidence for a developmental role for TLR4 in learning and memory. PloS One 2012;7:e47522. [DOI:10.1371/journal.pone.0047522]
34. Joshi R, Garabadu D, Teja GR, Krishnamurthy S. Silibinin ameliorates LPS-induced memory deficits in experimental animals. Neurobiol Learn Mem 2014;116:117-31. [DOI:10.1016/j.nlm.2014.09.006]
35. Ahmed HH. Modulatory effects of vitamin E, acetyl-l-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer's disease in rat model. Exp Toxicol Pathol 2012;64:549-56. [DOI:10.1016/j.etp.2010.11.012]
36. Blanca AJ, Ruiz-Armenta MV, Zambrano S, Miguel-Carrasco JL, Arias JL, Arévalo M, et al. Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: protective role of L-carnitine. Toxicol Lett 2016;241:9-18. [DOI:10.1016/j.toxlet.2015.11.007]
Send email to the article author

Add your comments about this article
Your username or Email:


XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Jamali-Raeufy N, Zeinivand M, Alizadeh F, Mehrabi S. Study on the effect of acetyl L-carnitine on cognitive and cellular disorders resulting from lipopolysaccharide-induced inflammation in male rats: emphasis on AKT / mTOR cell pathways and inflammation in the hippocampus. MEDICAL SCIENCES. 2021; 31 (4) :397-405
URL: http://tmuj.iautmu.ac.ir/article-1-1893-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 31, Issue 4 (WINTER 2021) Back to browse issues page
فصلنامه علوم پزشکی دانشگاه آزاد اسلامی واحد پزشکی تهران Medical Science Journal of Islamic Azad Univesity - Tehran Medical Branch
Persian site map - English site map - Created in 0.05 seconds with 30 queries by YEKTAWEB 4419