Trichostatin A Ameliorates Spatial Memory Deficits and Suppresses Hippocampal Pro- Inflammatory Cytokines in A Rat Model of Prenatal Stress

Document Type : Original Article

Authors

• Samireh Nemati
• Mohammad Amin Edalatmanesh

Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran

Abstract

Introduction: Maternal stress during pregnancy leads to neuroinflammation of the fetus and cognitive disorders in children. On the other side, Trichostatin A (TSA) as a histone deacetylase inhibitor has anti-inflammatory and neuroprotective effects. The aim of the present study was an evaluation of TSA effect on amelioration of spatial memory deficit and modification of pro-inflammatory cytokines in rat’s hippocampus of prenatal footshock stress model. Methods: In the present study, 24 pregnant Wistar rats were divided into 4 groups including control, PFS+Saline, PFS+TSA5, and PFS+TSA10. In order to induce prenatal footshock stress (PFS), the pregnant rats were subjected to electrical shock at 1 mA, 50 Hz for 2 seconds with 5 repetitions at 3-minute intervals from 12 to 18 days of pregnancy. Two hours before applying the shock intraperitoneal administration of TSA was performed daily. When the offsprings were one-month old, their spatial memory was assessed by the Morris water maze. Finally, the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured by ELISA method. Results: a reduction in spatial memory and an increase in the level of TNF-α, IL-1β, and IL-6 were observed in PFS+Saline group compared to the control. Besides, spatial learning showed a significant increase in TSA-treated groups compared to PFS+Saline. Conclusion: TSA with anti-inflammatory effects led to the reduction of hippocampal inflammatory cytokines and amelioration of spatial memory in offsprings who were exposed to stress in the prenatal period.

Keywords

• Prenatal Stress
• Inflammatory Cytokine
• Hippocampus
• Rat

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References

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2. Avishai- Eliner S, Brunson KL, Sandman CA, Baram TZ. Stressed-out or in (utero)?. Trends Neurosci. 2002; 25: 518- 524.
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4. Biala YN, Bogoch Y, Bejar C, Linial M, Weinstock M. Prenatal stress diminishes gender differences in behavior and in expression of hippocampal synaptic genes and proteins in rats. Hippocampus J. 2011; 21 (10): 1114- 1125.
5. Cui B, Wu M, She X, Liu H. Impulse noise exposure in rats causes cognitive deficits and changes in hippocampal neurotransmitter signaling and tau phosphorylation. Brain Res. 2011; 1427: 35- 43.
6. Chaaya N, Battle AR, Johnson LR. An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus. Neurosci Biobehav Rev. 2018; 92: 43- 54.
7. Ortiz JB, Conrad CD. The impact from the aftermath of chronic stress on hippocampal structure and function: Is there a recovery?. Front Neuroendocrinol. 2018; 49: 114- 123.
8. Gumusoglu SB, Fine RS, Murray SJ, Bittle JL, Stevens HE. The role of IL-6 in neurodevelopment after prenatal stress. Brain Behav Immun. 2017; 65: 274- 283.
9. Diz-Chaves Y, Pernía O, Carrero P, Garcia- Segura LM. Prenatal stress causes alterations in the morphology of microglia and the inflammatory response of the hippocampus of adult female mice. J Neuroinflammation. 2012; 9: 71.
10. Gómez- González B, Escobar A. Prenatal stress alters microglial development and distribution in postnatal rat brain. Acta Neuropathol. 2010; 119 (3): 303- 315.
11. Akhtar F, Rouse CA, Catano G, Montalvo M, Ullevig SL, Asmis R, et al. Acute maternal oxidant exposure causes susceptibility of the fetal brain to inflammation and oxidative stress. J Neuroinflammation. 2017; 14 (1): 195.
12. Schmauss C. The roles of class I histone deacetylases (HDACs) in memory, learning, and executive cognitive functions: A review. Neurosci Biobehav Rev. 2017; 83: 63- 71.
13. Penney J, Tsai LH. Histone deacetylases in memory and cognition. Sci Signal. 2014; 7 (355): re12.
14. Sharma S, Taliyan R, Ramagiri S. Histone deacetylase inhibitor, trichostatin A, improves learning and memory in high-fat diet-induced cognitive deficits in mice. J Mol Neurosci. 2015; 56 (1): 1- 11.
15. Akrami F, Edalatmanesh MA. Effect of sodium butyrate on working memory and serum level expression of neural growth factor in an animal model of prenatal stress. Shefaye Khatam J. 2016; 4 (3): 9- 17.
16. Rajabpour H, Edalatmanesh MA. The effect of erythropoietin on spatial memory and entorhinal cerebrocortical level of BDNF in rat model of intrauterine growth restriction. Rep Health Care. 2018; 4 (1): 1- 8.
17. Edalatmanesh MA, Yazdani M, Davoodi A, Rafiei S. Anxiolytic effect of lithium chloride in model of PTZ- induced seizure. Horizon Med Sci Univ J. 2018; 24 (2): 79- 87.
18. Zalosnik MI, Pollano A, Trujillo V, Suárez MM, Durando PE. Effect of maternal separation and chronic stress on hippocampal-dependent memory in young adult rats: evidence for the match-mismatch hypothesis. Stress J. 2014; 17 (5): 445- 450.
19. Rostamkhani F, Zardooz H, Parivar K, Hayati Roodbari M. Prenatal stress induces metabolic impairment in adolescent male Wistar rat. Adv Biores. 2013; 4 (1): 5- 11.
20. Segal M, Richter- Levin G, Maggio N. Stress- induced dynamic routing of hippocampal connectivity: A hypothesis. Hippocampus J. 2010; 20: 1332- 1338.
21. Charil A, Laplante DP, Vaillancourt C, King S. Prenatal stress and brain development. Brain Res Rev. 2010; 65 (1): 56- 79.
22. Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology (Berl). 2016; 233 (9): 1637- 1650.
23. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 48: 277- 286.
24. Wang B, Jin K. Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis. 2015; 30 (2): 355- 365.
25. Barrientos RM, Kitt MM, Watkins LR, Maier SF. Neuroinflammation in the normal aging hippocampus. Neuroscience J. 2015; 309: 84- 99.
26. Bittle J, Stevens HE. The role of glucocorticoid, interleukin-1β, and antioxidants in prenatal stress effects on embryonic microglia. J Neuroinflammation. 2018; 15 (1): 44.
27. Zhang X, Wang Q, Wang Y, Hu J, Jiang H, Cheng W, et al. Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats. J Neuroinflammation. 2012; 9: 71.
28. Diz- Chaves Y, Astiz M, Bellini MJ, Garcia- Segura LM. Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice. Brain Behav Immun. 2013; 28: 196- 206.
29. Hsing CH, Hung SK, Chen YC, Wei TS, Sun DP, Wang JJ, et al. Histone deacetylase inhibitor trichostatin a ameliorated endotoxin- induced neuroinflammation and cognitive dysfunction. Mediators Inflamm. 2015; 2015: 163140.
30. Vargas- López V, Lamprea MR, Múnera A. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment. Neurobiol Learn Mem. 2016; 134: 328- 338.
31. Zhang Q, Yang F, Li X, Wang L, Chu X, Zhang H, et al Trichostatin A inhibits inflammation in phorbol myristate acetate‑induced macrophages by regulating the acetylation of histone and/or non‑histone proteins. Mol Med Rep. 2016; 13 (1): 845- 852.
32. Zhang Q, Yang F, Li X, Wang LW, Chu XG, Zhang H, Gong ZJ. Trichostatin a protects against experimental acute- on- chronic liver failure in rats through regulating the acetylation of nuclear factor- κB. Inflammation J. 2015; 38 (3): 1364- 1373.
33. Chen HY, Li L, Fu ZJ. Histone deacetylase inhibitors trichostatin A and suberoylanilide hydroxamic acid attenuate ventilator-induced lung injury. Pharmazie J. 2014; 69 (1): 55- 59.

1.      Mclean M, Smith R. Corticotropin releasing hormone and human parturition. Reproduction J. 2001; 16 (8): 493- 501.

2.      Avishai- Eliner S, Brunson KL, Sandman CA, Baram TZ. Stressed-out or in (utero)?. Trends Neurosci. 2002; 25: 518- 524.

3.      Soares- Cunha C, Coimbra B, Borges S, Domingues AV, Silva D, Sousa N, et al. Mild prenatal stress causes emotional and brain structural modifications in rats of both sexes. Front Behav Neurosci. 2018; 12: 129.

4.      Biala YN, Bogoch Y, Bejar C, Linial M, Weinstock M. Prenatal stress diminishes gender differences in behavior and in expression of hippocampal synaptic genes and proteins in rats. Hippocampus J. 2011; 21 (10): 1114- 1125.

5.      Cui B, Wu M, She X, Liu H. Impulse noise exposure in rats causes cognitive deficits and changes in hippocampal neurotransmitter signaling and tau phosphorylation. Brain Res. 2011; 1427: 35- 43.

6.      Chaaya N, Battle AR, Johnson LR. An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus. Neurosci Biobehav Rev. 2018; 92: 43- 54.

7.      Ortiz JB, Conrad CD. The impact from the aftermath of chronic stress on hippocampal structure and function: Is there a recovery?. Front Neuroendocrinol. 2018; 49: 114- 123.

8.      Gumusoglu SB, Fine RS, Murray SJ, Bittle JL, Stevens HE. The role of IL-6 in neurodevelopment after prenatal stress. Brain Behav Immun. 2017; 65: 274- 283.

9.      Diz-Chaves Y, Pernía O, Carrero P, Garcia- Segura LM. Prenatal stress causes alterations in the morphology of microglia and the inflammatory response of the hippocampus of adult female mice. J Neuroinflammation. 2012; 9: 71.

10.  Gómez- González B, Escobar A. Prenatal stress alters microglial development and distribution in postnatal rat brain. Acta Neuropathol. 2010; 119 (3): 303- 315.

11.  Akhtar F, Rouse CA, Catano G, Montalvo M, Ullevig SL, Asmis R, et al. Acute maternal oxidant exposure causes susceptibility of the fetal brain to inflammation and oxidative stress.J Neuroinflammation. 2017; 14 (1): 195.

12.  Schmauss C. The roles of class I histone deacetylases (HDACs) in memory, learning, and executive cognitive functions: A review. Neurosci Biobehav Rev. 2017; 83: 63- 71.

13.  Penney J, Tsai LH. Histone deacetylases in memory and cognition. Sci Signal. 2014; 7 (355): re12.

14.  Sharma S, Taliyan R, Ramagiri S. Histone deacetylase inhibitor, trichostatin A, improves learning and memory in high-fat diet-induced cognitive deficits in mice. J Mol Neurosci. 2015; 56 (1): 1- 11.

15.  Akrami F, Edalatmanesh MA. Effect of sodium butyrate on working memory and serum level expression of neural growth factor in an animal model of prenatal stress. Shefaye Khatam J. 2016; 4 (3): 9- 17.

16.  Rajabpour H, Edalatmanesh MA. The effect of erythropoietin on spatial memory and entorhinal cerebrocortical level of BDNF in rat model of intrauterine growth restriction. Rep Health Care. 2018; 4 (1): 1- 8.

17.  Edalatmanesh MA, Yazdani M, Davoodi A, Rafiei S. Anxiolytic effect of lithium chloride in model of PTZ- induced seizure. Horizon Med Sci Univ J. 2018; 24 (2): 79- 87.

18.  Zalosnik MI, Pollano A, Trujillo V, Suárez MM, Durando PE. Effect of maternal separation and chronic stress on hippocampal-dependent memory in young adult rats: evidence for the match-mismatch hypothesis. Stress J. 2014; 17 (5): 445- 450.

19.  Rostamkhani F, Zardooz H, Parivar K, Hayati Roodbari M. Prenatal stress induces metabolic impairment in adolescent male Wistar rat. Adv Biores. 2013; 4 (1): 5- 11.

20.  Segal M, Richter- Levin G, Maggio N. Stress- induced dynamic routing of hippocampal connectivity: A hypothesis. Hippocampus J. 2010; 20: 1332- 1338.

21.  Charil A, Laplante DP, Vaillancourt C, King S. Prenatal stress and brain development. Brain Res Rev. 2010; 65 (1): 56- 79.

22.  Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology (Berl). 2016; 233 (9): 1637- 1650.

23.  Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 48: 277- 286.

24.  Wang B, Jin K. Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis. 2015; 30 (2): 355- 365.

25.  Barrientos RM, Kitt MM, Watkins LR, Maier SF. Neuroinflammation in the normal aging hippocampus. Neuroscience J. 2015; 309: 84- 99.

26.  Bittle J, Stevens HE. The role of glucocorticoid, interleukin-1β, and antioxidants in prenatal stress effects on embryonic microglia. J Neuroinflammation. 2018; 15 (1): 44.

27.  Zhang X, Wang Q, Wang Y, Hu J, Jiang H, Cheng W, et al. Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats. J Neuroinflammation. 2012; 9: 71.

28.  Diz- Chaves Y, Astiz M, Bellini MJ, Garcia- Segura LM. Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice. Brain Behav Immun. 2013; 28: 196- 206.

29.   Hsing CH, Hung SK, Chen YC, Wei TS, Sun DP, Wang JJ, et al. Histone deacetylase inhibitor trichostatin a ameliorated endotoxin- induced neuroinflammation and cognitive dysfunction. Mediators Inflamm. 2015; 2015: 163140.

30.   Vargas- López V, Lamprea MR, Múnera A. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment. Neurobiol Learn Mem. 2016; 134: 328- 338.

31.   Zhang Q, Yang F, Li X, Wang L, Chu X, Zhang H, et al Trichostatin A inhibits inflammation in phorbol myristate acetate‑induced macrophages by regulating the acetylation of histone and/or non‑histone proteins. Mol Med Rep. 2016; 13 (1): 845- 852.

32.  Zhang Q, Yang F, Li X, Wang LW, Chu XG, Zhang H, Gong ZJ. Trichostatin a protects against experimental acute- on- chronic liver failure in rats through regulating the acetylation of nuclear factor- κB. Inflammation J. 2015; 38 (3): 1364- 1373.

33.   Chen HY, Li L, Fu ZJ. Histone deacetylase inhibitors trichostatin A and suberoylanilide hydroxamic acid attenuate ventilator-induced lung injury. Pharmazie J. 2014; 69 (1): 55- 59.