Mehmet Deniz YENER, Tuncay ÇOLAK, Sema KURNAZ, Fatma Süreyya CEYLAN, Esra ACAR, Hale MARAL KIR

Effect of Chronic Unpredictable Mild Stress on Hippocampus and Serum Markers in Rats

Objective: Unpredictable stress is a common factor that we encounter in our daily lives. In this context, we wanted to investigate the morphological effects of a chronic unpredictable mild stress (CUMS) model on rat hippocampus and serum levels of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP). Materials and Methods: This study was carried out on 16 Wistar albino rat and divided into control and experiment groups. The CUMS model protocol was applied, and the morphological structures of the hippocampus were examined. The serum GFAP/BDNF levels were measured by ELISA method. Results: The mean BDNF level was 1.65 ± 0.17 ng/mL in the control group and 2.25 ± 0.29 ng/mL in the CUMS group. The mean GFAP level was 3.04 ± 0.45 ng/mL in the control group and 2.96 ± 0.58 ng/mL in the CUMS group. When the polymorph cell layer (PCL) in gyrus dentatus was examined; the mean number of cells in the control group was 20 ± 1.38 for the left PCL and 17 ± 1.35 for the right PCL. In the stress group; the mean number of cells in the polymorph cell layer of gyrus dentatus was 27 ± 2.08 cells for the left side and 23 ± 2.01 for the right side. Conclusions: As a result, morphological changes were observed in the gyrus dentatus region which has an important role in memory formation. The cells in the polymorph cell layer of gyrus dentatus underwent changes under stress.

Keywords:

Chronic stress, hippocampus, brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP),

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1. Selye H. Homeostasis and heterostasis. Perspect Biol Med 1973; 16(3): 441-5. google scholar
2. Davies KJA. Adaptive homeostasis. Mol Aspects Med 2016; 49: 1-7. google scholar
3. Lucassen PJ, Pruessner J, Sousa N, Almeida OFX, Van Dam AM, Rajkowska G, et al. Neuropathology of stress. Acta Neuropathol 2014; 127(1): 109-35. google scholar
4. O’Keefe J. A review of the hippocampal place cells. Prog Neurobiol 1979; 13(4): 419-39. google scholar
5. Jaroudi W, Garami J, Garrido S, Hornberger M, Keri S, Moustafa AA. Factors underlying cognitive decline in old age and Alzheimer’s disease: The role of the hippocampus. Rev Neurosci 2017; 28(7): 705-14. google scholar
6. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A 2001 ; 98(22): 12796-801. google scholar
7. Pfisterer U, Khodosevich K. Neuronal survival in the brain: neuron type-specific mechanisms. Cell Death Dis 2017; 8(3): e2643. google scholar
8. Willner P. The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiol Stress 2016;6: 78-93. google scholar
9. Kamphuis W, Mamber C, Moeton M, Kooijman L, Sluijs JA, Jansen AHP, et al. GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PLoS One 2012; 7(8): e42823. google scholar
10. Quesseveur G, David DJ, Gaillard MC, Pla P, Wu MV, Nguyen HT, et al. BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities. Transl Psychiatry 2013; 3(4): e253. google scholar
11. Kojima M, Mizui T. Chapter Two - BDNF propeptide: A novel modulator of synaptic plasticity. In: Litwack G, editor. Vitamins and Hormones. Academic Press 2017; vol. 104, p. 19-28. google scholar
12. Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl) 1987; 93(3): 358-64. google scholar
13. Qin C, Bai Y, Zeng Z, Wang L, Luo Z, Wang S, et al. The cutting and floating method for paraffin-embedded tissue for sectioning. J Vis Exp 2018; (139): 58288. google scholar
14. Vallieres L, Campbell IL, Gage FH, Sawchenko PE. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 2002; 22(2): 486-92. google scholar
15. Park H, Poo M ming. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 2013; 14(1): 7-23. google scholar
16. Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol 2011; 93(3): 421-43. google scholar
17. Qiao H, Li MX, Xu C, Chen HB, An SC, Ma XM. Dendritic spines in depression: What we learned from animal models. Neural Plast 2016; 2016: 8056370. google scholar
18. Liu D, Wang Z, Gao Z, Xie K, Zhang Q, Jiang H, et al. Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behav Brain Res 2014; 271: 116-21. google scholar
19. Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 2011; 476(7361): 458-61. google scholar
20.Kirby ED, Muroy SE, Sun WG, Covarrubias D, Leong MJ, Barchas LA, et al. Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2. Fernald R, editor. eLife. 2013; 2: e00362. google scholar
21. Toni N, Schinder AF. Maturation and functional integration of new granule cells into the adult hippocampus. Cold Spring Harb Perspect Biol 2016; 8(1): a018903. google scholar
22. Drew LJ, Fusi S, Hen R. Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus? Learn Mem 2013; 20(12): 710-29. google scholar