Flaxseed oil (Linum Usitatissimum) attenuates restraint stress-induced depressive-like behavior: Upregulation of neurotrophic factors in CA1 region of hippocampus
DOI:
https://doi.org/10.22317/jcms.v7i1.945Keywords:
Depression, Immobility stress, Flaxseed, Neurotrophic factors, AntioxidantAbstract
Objectives: In this study, we aimed to evaluate the anti-depressant effects of FS oil on the depressive-like behavior following immobility stress in mice.
Methods: In this study, 32 male mice were divided into four groups: Control group; FS oil group; Model group: The immobility stress (using falcon for 20 day, 6 hours a day) + feeding with normal saline by oral gavage for another 20 days); Model+FS group: The immobility stress + feeding with 0.2 ml/kg of FS oil by oral gavage for another 20 days. At the end, all mice were evaluated with tail suspension test (TST) and sacrificed through cardiac puncture method. The brain was isolated and prepared for molecular and histopathological studies.
Results: The gene expression and protein level of BGNF and GDNF were significantly increased in FS oil treated groups (P<0.05). In microscopic evaluations, the number of dead neurons significantly deceased in FS group (P<0.05). TST results showed a significant decrease in immobility time and depressive-like behaviors in FS oil treated group (P<0.05).
Conclusion: FS oil feeding may be effective in treatment of depressive like disorders through its anti-oxidative and neurotrophic promoting features. Therefore, it can be used as an appropriate alternative choice in daily diet to prevent depression in clinical investigations.
References
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9.       Sjors Dahlman A, Blennow K, Zetterberg H, Glise K, Jonsdottir IH. Growth factors and neurotrophins in patients with stress-related exhaustion disorder. Psychoneuroendocrinology. 2019;109:104415.
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15.     Bagheri A, Talei S, Hassanzadeh N, Mokhtari T, Akbari M, Malek F, et al. The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF. Acta Med Iran. 2017;55(12):785-92.
16.     Connor WE. Alpha-linolenic acid in health and disease. Am J Clin Nutr. 1999;69(5):827-8.
17.     Tsybko AS, Il'chibaeva TV, Kondaurova EM, Bazovkina DV, Naumenko VS. [The effect of central administration of the neurotrophic factors BDNF and GDNF on the functional activity and expression of the serotonin 5-HT2A receptors in mice genetically predisposed to depressive-like behavior]. Mol Biol (Mosk). 2014;48(6):983-9.
18.     Can A, Dao DT, Terrillion CE, Piantadosi SC, Bhat S, Gould TD. The tail suspension test. J Vis Exp. 2012(59):e3769.
19.     Son H, Yang JH, Kim HJ, Lee DK. A chronic immobilization stress protocol for inducing depression-like behavior in mice. JoVE (Journal of Visualized Experiments). 2019(147):e59546.
20.     Liu L, Zhou X, Zhang Y, Liu Y, Yang L, Pu J, et al. The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression. Behavioural brain research. 2016;305:148-56.
21.     Duman RS. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci. 2009;11(3):239-55.
22.     Yanik M, Erel O, Kati M. The relationship between potency of oxidative stress and severity of depression. Acta Neuropsychiatrica. 2004;16(4):200-3.
23.     Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;48:102-11.
24.     Popova N, Ilchibaeva T, Naumenko V. Neurotrophic factors (BDNF and GDNF) and the serotonergic system of the brain. Biochemistry (Moscow). 2017;82(3):308-17.
25.     Mokhtari T, Akbari M, Malek F, Kashani IR, Rastegar T, Noorbakhsh F, et al. Improvement of memory and learning by intracerebroventricular microinjection of T3 in rat model of ischemic brain stroke mediated by upregulation of BDNF and GDNF in CA1 hippocampal region. DARU Journal of Pharmaceutical Sciences. 2017;25(1):4.
26.     Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature neuroscience. 2006;9(4):519-25.
27.     Park Y-M, Lee B-H. Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant Treatment in Female Outpatients with Major Depressive Disorder. Psychiatry Investig. 2018;15(8):818-23.
28.     Angelucci F, Aloe L, Jiménez-Vasquez P, Mathé AA. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. International Journal of Neuropsychopharmacology. 2003;6(3):225-31.
29.     Tunca Z, Ozerdem A, Ceylan D, Yalçın Y, Can G, Resmi H, et al. Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: the role of lithium. Journal of affective disorders. 2014;166:193-200.
30.     Varela RB, Valvassori SS, Lopes-Borges J, Mariot E, Dal-Pont GC, Amboni RT, et al. Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats. Journal of Psychiatric Research. 2015;61:114-21.
31.     Ashaari Z, Hadjzadeh M-A-R, Hassanzadeh G, Alizamir T, Yousefi B, Keshavarzi Z, et al. The Flavone Luteolin Improves Central Nervous System Disorders by Different Mechanisms: A Review. Journal of Molecular Neuroscience. 2018;65(4):491-506.
32.     Ghaffari N, Hassanzadeh G, Nowrouzi A, Gholaminejhad M, Mokhtari T, Seifali R, et al. Antioxidative and anti-inflammatory effects of Cichorium intybus L. seed extract in ischemia/reperfusion injury model of rat spinal cord. Journal of Contemporary Medical Sciences. 2018;4(4).
33.     Mokhtari T, Hussein Osman H-E, El-Meghawry El-Kenawy A, Dashti N. Ameliorative effect of virgin olive oil against nephrotoxicity following sub-chronic administration of ethephon in male rats. Journal of Traditional and Complementary Medicine. 2020;10(5):487-95.
34.     Mokhtari T, Faghir Ghanesefat H, Hassanzadeh G, Moayeri A, Haeri SMJ, Rezaee Kanavee A, et al. Effects of Flaxseed oil supplementation on renal dysfunction due to ischemia/reperfusion in rat. Ilam-University-of-Medical-Sciences. 2017;4(1):22-9.
35.     Goyal A, Sharma V, Upadhyay N, Gill S, Sihag M. Flax and flaxseed oil: an ancient medicine & modern functional food. J Food Sci Technol. 2014;51(9):1633-53.
36.      Gholaminejhad M, Arabzadeh S, Akbari M, Mohamadi Y, Hassanzadeh G. Anti-oxidative and neuroprotective effects of flaxseed on experimental unilateral spinal cord injury in rat. Journal of Contemporary Medical Sciences. 2017;3(10):213-7.
37.      Gholaminejhad M, Hassanzadeh G, Akbari M. O2: Flaxseed Reduces Proinflammatory Factors IL-1β, IL-18 and TNF-α in Injured Spinal Cord Rat Model. Shafaye Khatam neuroscience journal 2018;6(2):2-.
38.     Navaie F, Hassanzadeh G, Mahakizadeh S, Mehrannia K, Alizamir T, Dashti N, et al. Anti-Oxidative and Neuroprotective Effects of Supplementary Flaxseed on Oxidative Damage in the Hippocampus Area of a Rat Model of Hypoxia. Archives of Neuroscience. 2018;5(4).
39.        Hadjighassem M, Kamalidehghan B, Shekarriz N, Baseerat A, Molavi N, Mehrpour M, et al. Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans. Nutrition journal. 2015;14(1):20.
40.     Razi SS, Latif MJ, Li X, Afthinos JN, Ippagunta N, Schwartz G, et al. Dietary flaxseed protects against lung ischemia reperfusion injury via inhibition of apoptosis and inflammation in a murine model. Journal of Surgical Research. 2011;171(1):e113-e21.
41.     Rahmati-Ahmadabad S, Azarbayjani M, Nasehi M. The effects of high-intensity interval training with supplementation of flaxseed oil on BDNF mRNA expression and pain feeling in male rats. Annals of Applied Sport Science. 2017;5(4):1-12.
42.     Bagheri A, Talei S, Hassanzadeh N, Mokhtari T, Akbari M, Malek F, et al. The neuroprotective effects of flaxseed oil supplementation on functional motor recovery in a model of ischemic brain stroke: upregulation of BDNF and GDNF. Acta Medica Iranica. 2017:785-92.
2.       Sapse AT. Stress, cortisol, interferon and "stress" diseases. I. Cortisol as the cause of "stress" diseases. Med Hypotheses. 1984;13(1):31-44.
3.       Carpenter WT, Jr., Gruen PH. Cortisol's effects on human mental functioning. J Clin Psychopharmacol. 1982;2(2):91-101.
4.       Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci. 2007;10(9):1089-93.
5.       Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DD. Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science. 1999;286(5448):2358-61.
6.       Emon MPZ, Das R, Nishuty NL, Shalahuddin Qusar MMA, Bhuiyan MA, Islam MR. Reduced serum BDNF levels are associated with the increased risk for developing MDD: a case-control study with or without antidepressant therapy. BMC Res Notes. 2020;13(1):83.
7.       Numakawa T, Adachi N, Richards M, Chiba S, Kunugi H. Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system. Neuroscience. 2013;239:157-72.
8.       Ducray A, Krebs SH, Schaller B, Seiler RW, Meyer M, Widmer HR. GDNF family ligands display distinct action profiles on cultured GABAergic and serotonergic neurons of rat ventral mesencephalon. Brain research. 2006;1069(1):104-12.
9.       Sjors Dahlman A, Blennow K, Zetterberg H, Glise K, Jonsdottir IH. Growth factors and neurotrophins in patients with stress-related exhaustion disorder. Psychoneuroendocrinology. 2019;109:104415.
10.     Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002;109(2):143-8.
11.     Liu RJ, Aghajanian GK. Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy. Proc Natl Acad Sci U S A. 2008;105(1):359-64.
12.     Popoli M, Yan Z, McEwen BS, Sanacora G. The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci. 2011;13(1):22-37.
13.     Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A. The impact of stress on body function: A review. EXCLI J. 2017;16:1057-72.
14.     Popova NK, Ilchibaeva TV, Naumenko VS. Neurotrophic Factors (BDNF and GDNF) and the Serotonergic System of the Brain. Biochemistry (Mosc). 2017;82(3):308-17.
15.     Bagheri A, Talei S, Hassanzadeh N, Mokhtari T, Akbari M, Malek F, et al. The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF. Acta Med Iran. 2017;55(12):785-92.
16.     Connor WE. Alpha-linolenic acid in health and disease. Am J Clin Nutr. 1999;69(5):827-8.
17.     Tsybko AS, Il'chibaeva TV, Kondaurova EM, Bazovkina DV, Naumenko VS. [The effect of central administration of the neurotrophic factors BDNF and GDNF on the functional activity and expression of the serotonin 5-HT2A receptors in mice genetically predisposed to depressive-like behavior]. Mol Biol (Mosk). 2014;48(6):983-9.
18.     Can A, Dao DT, Terrillion CE, Piantadosi SC, Bhat S, Gould TD. The tail suspension test. J Vis Exp. 2012(59):e3769.
19.     Son H, Yang JH, Kim HJ, Lee DK. A chronic immobilization stress protocol for inducing depression-like behavior in mice. JoVE (Journal of Visualized Experiments). 2019(147):e59546.
20.     Liu L, Zhou X, Zhang Y, Liu Y, Yang L, Pu J, et al. The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression. Behavioural brain research. 2016;305:148-56.
21.     Duman RS. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci. 2009;11(3):239-55.
22.     Yanik M, Erel O, Kati M. The relationship between potency of oxidative stress and severity of depression. Acta Neuropsychiatrica. 2004;16(4):200-3.
23.     Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;48:102-11.
24.     Popova N, Ilchibaeva T, Naumenko V. Neurotrophic factors (BDNF and GDNF) and the serotonergic system of the brain. Biochemistry (Moscow). 2017;82(3):308-17.
25.     Mokhtari T, Akbari M, Malek F, Kashani IR, Rastegar T, Noorbakhsh F, et al. Improvement of memory and learning by intracerebroventricular microinjection of T3 in rat model of ischemic brain stroke mediated by upregulation of BDNF and GDNF in CA1 hippocampal region. DARU Journal of Pharmaceutical Sciences. 2017;25(1):4.
26.     Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature neuroscience. 2006;9(4):519-25.
27.     Park Y-M, Lee B-H. Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant Treatment in Female Outpatients with Major Depressive Disorder. Psychiatry Investig. 2018;15(8):818-23.
28.     Angelucci F, Aloe L, Jiménez-Vasquez P, Mathé AA. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. International Journal of Neuropsychopharmacology. 2003;6(3):225-31.
29.     Tunca Z, Ozerdem A, Ceylan D, Yalçın Y, Can G, Resmi H, et al. Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: the role of lithium. Journal of affective disorders. 2014;166:193-200.
30.     Varela RB, Valvassori SS, Lopes-Borges J, Mariot E, Dal-Pont GC, Amboni RT, et al. Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats. Journal of Psychiatric Research. 2015;61:114-21.
31.     Ashaari Z, Hadjzadeh M-A-R, Hassanzadeh G, Alizamir T, Yousefi B, Keshavarzi Z, et al. The Flavone Luteolin Improves Central Nervous System Disorders by Different Mechanisms: A Review. Journal of Molecular Neuroscience. 2018;65(4):491-506.
32.     Ghaffari N, Hassanzadeh G, Nowrouzi A, Gholaminejhad M, Mokhtari T, Seifali R, et al. Antioxidative and anti-inflammatory effects of Cichorium intybus L. seed extract in ischemia/reperfusion injury model of rat spinal cord. Journal of Contemporary Medical Sciences. 2018;4(4).
33.     Mokhtari T, Hussein Osman H-E, El-Meghawry El-Kenawy A, Dashti N. Ameliorative effect of virgin olive oil against nephrotoxicity following sub-chronic administration of ethephon in male rats. Journal of Traditional and Complementary Medicine. 2020;10(5):487-95.
34.     Mokhtari T, Faghir Ghanesefat H, Hassanzadeh G, Moayeri A, Haeri SMJ, Rezaee Kanavee A, et al. Effects of Flaxseed oil supplementation on renal dysfunction due to ischemia/reperfusion in rat. Ilam-University-of-Medical-Sciences. 2017;4(1):22-9.
35.     Goyal A, Sharma V, Upadhyay N, Gill S, Sihag M. Flax and flaxseed oil: an ancient medicine & modern functional food. J Food Sci Technol. 2014;51(9):1633-53.
36.      Gholaminejhad M, Arabzadeh S, Akbari M, Mohamadi Y, Hassanzadeh G. Anti-oxidative and neuroprotective effects of flaxseed on experimental unilateral spinal cord injury in rat. Journal of Contemporary Medical Sciences. 2017;3(10):213-7.
37.      Gholaminejhad M, Hassanzadeh G, Akbari M. O2: Flaxseed Reduces Proinflammatory Factors IL-1β, IL-18 and TNF-α in Injured Spinal Cord Rat Model. Shafaye Khatam neuroscience journal 2018;6(2):2-.
38.     Navaie F, Hassanzadeh G, Mahakizadeh S, Mehrannia K, Alizamir T, Dashti N, et al. Anti-Oxidative and Neuroprotective Effects of Supplementary Flaxseed on Oxidative Damage in the Hippocampus Area of a Rat Model of Hypoxia. Archives of Neuroscience. 2018;5(4).
39.        Hadjighassem M, Kamalidehghan B, Shekarriz N, Baseerat A, Molavi N, Mehrpour M, et al. Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans. Nutrition journal. 2015;14(1):20.
40.     Razi SS, Latif MJ, Li X, Afthinos JN, Ippagunta N, Schwartz G, et al. Dietary flaxseed protects against lung ischemia reperfusion injury via inhibition of apoptosis and inflammation in a murine model. Journal of Surgical Research. 2011;171(1):e113-e21.
41.     Rahmati-Ahmadabad S, Azarbayjani M, Nasehi M. The effects of high-intensity interval training with supplementation of flaxseed oil on BDNF mRNA expression and pain feeling in male rats. Annals of Applied Sport Science. 2017;5(4):1-12.
42.     Bagheri A, Talei S, Hassanzadeh N, Mokhtari T, Akbari M, Malek F, et al. The neuroprotective effects of flaxseed oil supplementation on functional motor recovery in a model of ischemic brain stroke: upregulation of BDNF and GDNF. Acta Medica Iranica. 2017:785-92.
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Published
2021-02-26
How to Cite
Talei, S., Mokhtari, T., Asadi, I., Arab, L., Hassanzadeh, N., Hosseinjani, E., & Hassanzadeh, G. (2021). Flaxseed oil (Linum Usitatissimum) attenuates restraint stress-induced depressive-like behavior: Upregulation of neurotrophic factors in CA1 region of hippocampus. Journal of Contemporary Medical Sciences, 7(1), 61–65. https://doi.org/10.22317/jcms.v7i1.945
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