Changes of serum level of acetylcholinesterase enzyme in lipopolysaccharide-induced model of depression in mice

Document Type: Research Paper


1 Department of Biology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

2 Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran

3 Department of Biology, School of Science, Razi University, Kermanshah, Iran

4 Neurophysiology Research Center, Shahed University, Tehran, Iran


Background and Objective: Depression is a common disorder, especially in developed countries. Functional changes of cholinesterase are involved in pathogenesis of some brain disorders. Until now, exact association of these changes with depression has not been determined. This study was conducted to evaluate the changes of serum cholinesterase in lipopolysaccharide (LPS)-induced model of depression in male mice.
Materials and Methods: Male mice (n = 48) were divided into 2 groups of control and LPS. For induction of depression, LPS (0.5 mg/kg; i.p.) was injected 24 h before the experiments. Open field, forced swimming, and tail suspension tests were used for behavioral assessment. Finally, serum cholinesterase activity was determined using biochemical method.
Results: LPS injection significantly decreased travelled distance in open field test (p<0.05) and increased immobility duration in forced swimming and tail suspension tests (p<0.01). In addition, serum cholinesterase showed a significant decrease in LPS subgroups versus control (p<0.05).
Conclusion: Our data showed that LPS could induce a valid model of depression and changes of cholinesterase are in part involved in development of its complications.


1.       Deyama S, Ishikawa Y, Yoshikawa K, Shimoda K, Ide S, Satoh M, et al. Resolvin D1 and D2 reverse lipopolysaccharide-induced depression-like behaviors through the mTORC1 signaling pathway. The International Journal of Neuropsychopharmacology 2017.

2.       Lawson MA, Parrott JM, McCusker RH, Dantzer R, Kelley KW, O'Connor JC. Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors. Journal of Neuroinflammation 2013;10:87.

3.       Ma M, Ren Q, Zhang JC, Hashimoto K. Effects of Brilliant Blue G on Serum Tumor Necrosis Factor-alpha Levels and Depression-like Behavior in Mice after Lipopolysaccharide Administration. Clinical Psychopharmacology and Neuroscience 2014;12(1):31-6.

4.       Maldonado RF, Sa-Correia I, Valvano MA. Lipopolysaccharide modification in Gram-negative bacteria during chronic infection. FEMS microbiology reviews 2016;40(4):480-93.

5.       Kracmarova A, Drtinova L, Pohanka M. Possibility of Acetylcholinesterase Overexpression in Alzheimer Disease Patients after Therapy with Acetylcholinesterase Inhibitors. Acta Medica (Hradec Kralove) 2015;58(2):37-42.

6.       Shi QX, Yang LK, Shi WL, Wang L, Zhou SM, Guan SY, et al. The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress. Molecular Brain 2017;10(1):38.

7.       Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. European Journal of Pharmacology 1978;47(4):379-91.

8.       Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985;85(3):367-70.

9.       Ming Z, Sawicki G, Bekar LK. Acute systemic LPS-mediated inflammation induces lasting changes in mouse cortical neuromodulation and behavior. Neuroscience Letters 2015;590:96-100.

10.    Bluthe RM, Laye S, Michaud B, Combe C, Dantzer R, Parnet P. Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. European Journal of Neuroscience 2000;12(12):4447-56.

11.    Carvalho FB, Gutierres JM, Bueno A, Agostinho P, Zago AM, Vieira J, et al. Anthocyanins control neuroinflammation and consequent memory dysfunction in mice exposed to lipopolysaccharide. Molecular Neurobiology 2016.

12.    Andrade VS, Rojas DB, de Andrade RB, Kim TDH, Vizuete AF, Zanatta A, et al. A Possible Anti-Inflammatory Effect of Proline in the Brain Cortex and Cerebellum of Rats. Molecular Neurobiology 2017.

13.    Ahshin-Majd S, Zamani S, Kiamari T, Kiasalari Z, Baluchnejadmojarad T, Roghani M. Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms. Peptides 2016;86:102-11.

14.    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. European Journal of Pharmacology 2017;795:13-21.

15.    Sohanaki H, Baluchnejadmojarad T, Nikbakht F, Roghani M. Pelargonidin Improves Passive Avoidance Task Performance in a Rat Amyloid Beta25-35 Model of Alzheimer’s Disease Via Estrogen Receptor Independent Pathways. Acta Medica Iranica  2016:245-50.

16.    Mokhtari Z, Baluchnejadmojarad T, Nikbakht F, Mansouri M, Roghani M. Riluzole ameliorates learning and memory deficits in Abeta25-35-induced rat model of Alzheimer's disease and is independent of cholinoceptor activation. Biomedicine and Pharmacotherapy 2017;87:135-44.

17.    Mao XY, Cao DF, Li X, Yin JY, Wang ZB, Zhang Y, et al. Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats. International Journal of Molecular Sciences 2014;15(5):7667-83.

18.    Liu ZH, Chen HG, Wu PF, Yao Q, Cheng HK, Yu W, et al. Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice. Evidence-based Complementary and Alternative Medicine 2015;2015:873243.

19.    Tyagi E, Agrawal R, Nath C, Shukla R. Effect of melatonin on neuroinflammation and acetylcholinesterase activity induced by LPS in rat brain. European Journal of Pharmacology 2010;640(1-3):206-10.

20.    Silverman HA, Dancho M, Regnier-Golanov A, Nasim M, Ochani M, Olofsson PS, et al. Brain region-specific alterations in the gene expression of cytokines, immune cell markers and cholinergic system components during peripheral endotoxin-induced inflammation. Molecular Medicine 2014;20:601-11.

21.    Joshi R, Garabadu D, Teja GR, Krishnamurthy S. Silibinin ameliorates LPS-induced memory deficits in experimental animals. Neurobiology of Learning and Memory 2014;116:117-31.