Sinan SARAL, Ayşegül SUMER, Ali Koray KAYA, Aykut ÖZTÜRK, Atilla TOPCU

Chronic restraint stress impairs spatial memory while decreasing hippocampal BDNF levels in rats

Aim: This study investigated the potential role of chronic restraint stress (CRS) on spatial memory, recognition memory, brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels in young adult rats. Material and Methods: In the study, 16 female rats of 12 weeks old were used. Rats were divided into two groups as control and CRS (n=8). CRS was applied 5 hours a day for 21 days. Following the end of CRS, recognition memory of rats was evaluated with new object recognition test (NORT) and spatial memory was evaluated with Morris water maze (MWM) test. At the end of the study, rats were euthanized and hippocampal tissue homogenates were obtained. Hippocampal BDNF and ACh levels were determined by ELISA method. Results: Exposure to CRS did not significantly change the exploratory behavior and discrimination index of rats (p > 0.05). In the test phase in which spatial memory was evaluated, CRS decreased the time spent in the target quadrant (p > 0.01). There was no significant difference between days in the training phase. CRS significantly decreased BDNF level in hippocampus (p > 0.05). Hippocampal ACh levels were not statistically significant (p > 0.05). Conclusions: CRS weakened cognitive functions in rats. This effect was mainly accompanied by a decrease in hippocampal BDNF levels. Our findings point to the potential role of BDNF in understanding the molecular mechanism of CRS-induced cognitive impairment.

PDF

___

1. Wang Y, Kan H, Yin Y, et al. Protective effects of ginsenoside Rg1 on chronic restraint stress induced learning and memory impairments in male mice. Pharmacol Biochem Behav 2014;120:73– 81.
2. Nagata K, Nakashima-Kamimura N, Mikami T, et al. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology 2009;34:501-8.
3. Bhagya VR, Srikumar BN, Veena J, Shankaranarayana Rao BS. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits. J Neurosci Res 2017;95:1602–10.
4. Miao Z, Wang Y, Sun Z. The relationships between stress, mental disorders, and epigenetic regulation of bdnf. Int J Mol Sci 2020;21:1375.
5. Xu H, Chen Z, He J, et al. Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus. Hippocampus 2006;16:551–9.
6. Yeh CM, Huang CC, Hsu K Sen. Prenatal stress alters hippocampal synaptic plasticity in young rat offspring through preventing the proteolytic conversion of pro-brain-derived neurotrophic factor (BDNF) to mature BDNF. J Physiol 2012;590:991–1010.
7. Eisch AJ, Petrik D. Depression and hippocampal neurogenesis: A road to remission? Science 2012;338:72–5.
8. Zhao D, Xu X, Pan L, et al. Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress. J Neuroinflammation 2017;14:1–15.
9. Hampel H, Mesulam MM, Cuello AC, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 2018;141:1917–33.
10. Paul S, Jeon WK, Bizon JL, Han JS. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment. Front Aging Neurosci 2015;7:1–11.
11. Croxson PL, Kyriazis DA, Baxter MG. Cholinergic modulation of a specific memory function of prefrontal cortex. Nat Neurosci 2011;14:1510–2.
12. Sántha P, Pákáski M, Fazekas ÖC, et al. Restraint stress in rats alters gene transcription and protein translation in the hippocampus. Neurochem Res 2012;37:958–64.
13. Saral S, Topçu A, Alkanat M, et al. Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction. Behav Brain Res 2021;408:113290.
14. Sun DS, Zhong G, Cao HX, et al. Repeated restraint stress led to cognitive dysfunction by nmda receptor-mediated hippocampal CA3 dendritic spine impairments in juvenile sprague-dawley rats. Front Mol Neurosci 2020;13:1–12.
15. Zhang Q, Wang X, Bai X, et al. Resveratrol reversed chronic restraint stress-induced impaired cognitive function in rats. Mol Med Rep 2017;16:2095–100.
16. Guedri K, Frih H, Chettoum A, Rouabhi R. Chronic restraint stress induced neurobehavioral alterations and histological changes in rat. Toxicol Environ Health Sci 2017;9:123–9.
17. Kim EJ, Pellman B, Kim JJ. Stress effects on the hippocampus: A critical review. Learn Mem 2015;22:411–6.
18. Yamada K, Nabeshima T. Current Perspective Brain-Derived Neurotrophic Factor / TrkB Signaling in Memory Processes. J Pharmocol Sci 2003;91:267–70.
19. Kowiański P, Lietzau G, Czuba E, et al. BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol 2018;38:579–93.
20. 20. Kwon DH, Kim BS, Chang H, et al. Exercise ameliorates cognition impairment due to restraint stress-induced oxidative insult and reduced BDNF level. Biochem Biophys Res Commun 2013;434:245–51.
21. Murakami S, Imbe H, Morikawa Y, et al. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 2005;53:129–39.
22. Radecki DT, Brown LM, Martinez J, Teyler TJ. BDNF protects against stress-induced impairments in spatial learning and memory and LTP. Hippocampus 2005;15:246–53. 529