TSPO ligand etifoxine enhances memory reconsolidation in novel object recognition memory
Abstract
Etifoxine is a mixed drug ligand of TSPO and GABAA. It plays an important role in the treatment of anxiety disorders by promoting the synthesis of neurosteroids. Anxiety disorders are closely related to learning and memory. Etifoxine was evaluated in novel object recognition (NOR) task mouse model by injecting etifoxine into the abdominal cavity. However, few studies have investigated the effect of etifoxine on memory reconsolidation. The behavioral results showed that etifoxine-enhanced NOR memory performance when injected into mice 0 h after reactivation rather than following a 6 h delay. Conversely, administering etifoxine 24 h after sampling without reactivation did not affect NOR memory performance. Notably, etifoxine enhances memory performance not because of its effect on nonspecific responses, such as motor activity and exploratory behavior. The transcriptomic results suggested that etifoxine could regulate learning and memory-related expression genes such as CCL5, CSF3R, CXCL1, Fos, ITIH2, LRG1 and RGS1, which enhanced learning and memory in mice. In conclusion, etifoxine can improve memory reconsolidation in mice by regulating memory-related genes in the hippocampus.
References
1. Przybyslawski J, Sara SJ. Reconsolidation of memory after its reactivation. Behav Brain Res 1997; 84 (1-2): 241-246.
2. Sharma R, Sahota P, Thakkar MM. Sleep Loss Immediately After Fear Memory Reactivation Attenuates Fear Memory Reconsolidation. Neuroscience. 2020; 428: 70-75. doi: 10.1016/j.neuroscience.2019.12.024
3. Schäble S, Huston JP, Barros M, et al. The NK3 receptor agonist senktide ameliorates scopolamine-induced deficits in memory for object, place and temporal order. Neurobiology of Learning and Memory. 2012; 97(2): 235-240. doi: 10.1016/j.nlm.2011.12.007
4. Tronson NC, Taylor JR. Molecular mechanisms of memory reconsolidation. Nature Reviews Neuroscience. 2007; 8(4): 262-275. doi: 10.1038/nrn2090
5. Haubrich J, Nader K. Memory reconsolidation. Curr Top Behav Neurosci. 2018; 37: 151-176. doi: 10.1007/7854_2016_463
6. Stein DJ. Etifoxine Versus Alprazolam for the Treatment of Adjustment Disorder with Anxiety: a Randomized Controlled Trial. Advances in Therapy. 2015; 32(1): 57-68. doi: 10.1007/s12325-015-0176-6
7. Girard C, Liu S, Cadepond F, et al. Etifoxine improves peripheral nerve regeneration and functional recovery. Proceedings of the National Academy of Sciences. 2008; 105(51): 20505-20510. doi: 10.1073/pnas.0811201106
8. Zhang H, Ma L, Guo W zhi, et al. TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice. Brain Research Bulletin. 2020; 165: 178-184. doi: 10.1016/j.brainresbull.2020.10.013
9. Gunn BG, Cunningham L, Mitchell SG, et al. GABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response. Frontiers in Neuroendocrinology. 2015; 36: 28-48. doi: 10.1016/j.yfrne.2014.06.001
10. Godinho AF, de Oliveira Souza AC, Carvalho CC, et al. Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats. Physiology & Behavior. 2016; 165: 28-34. doi: 10.1016/j.physbeh.2016.06.035
11. Katz RJ, Liebler L. GABA involvement in memory consolidation: Evidence from posttrial amino-oxyacetic acid. Psychopharmacology. 1978; 56(2): 191-193. doi: 10.1007/bf00431848
12. Toyoda H, Katagiri A, Kato T, et al. Intranasal Administration of Rotenone Reduces GABAergic Inhibition in the Mouse Insular Cortex Leading to Impairment of LTD and Conditioned Taste Aversion Memory. International Journal of Molecular Sciences. 2020; 22(1): 259. doi: 10.3390/ijms22010259
13. Lueptow LM. Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. Journal of Visualized Experiments. 2017; (126). doi: 10.3791/55718
14. Riban V, Meunier J, Buttigieg D, et al. In Vitro and In Vivo Neuroprotective Effects of Etifoxine in β-Amyloidinduced Toxicity Models. CNS & Neurological Disorders - Drug Targets. 2020; 19(3): 227-240. doi: 10.2174/1871527319666200601151007
15. Wang L, Tan Y, Wang H, et al. Urocanic acid facilitates acquisition of object recognition memory in mice. Physiology & Behavior. 2023; 266: 114201. doi: 10.1016/j.physbeh.2023.114201
16. Yu XD, Mo YX, He Z, et al. Urocanic acid enhances memory consolidation and reconsolidation in novel object recognition task. Biochemical and Biophysical Research Communications. 2021; 579: 62-68. doi: 10.1016/j.bbrc.2021.09.055
17. Bellfy L, Kwapis JL. Molecular Mechanisms of Reconsolidation-Dependent Memory Updating. International Journal of Molecular Sciences. 2020; 21(18): 6580. doi: 10.3390/ijms21186580
18. Osorio-Gómez D, Saldivar-Mares KS, Perera-López A, et al. Early memory consolidation window enables drug induced state-dependent memory. Neuropharmacology. 2019; 146: 84-94. doi: 10.1016/j.neuropharm.2018.11.033
19. Tian S, Pan S, You Y. Nicotine enhances the reconsolidation of novel object recognition memory in rats. Pharmacology Biochemistry and Behavior. 2015; 129: 14-18. doi: 10.1016/j.pbb.2014.11.019
20. Liang P, Manelis A, Liu X, et al. Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia. Neuroscience Letters. 2012; 522(2): 113-117. doi: 10.1016/j.neulet.2012.06.019
21. Thanapreedawat P, Kobayashi H, Inui N, et al. GABA Affects Novel Object Recognition Memory and Working Memory in Rats. Journal of Nutritional Science and Vitaminology. 2013; 59(2): 152-157. doi: 10.3177/jnsv.59.152
22. Alhowail A. Mechanisms Underlying Cognitive Impairment Induced by Prenatal Alcohol Exposure. Brain Sciences. 2022; 12(12): 1667. doi: 10.3390/brainsci12121667
23. Zhang J, Yetton B, Whitehurst LN, et al. The effect of zolpidem on memory consolidation over a night of sleep. Sleep. 2020; 43(11). doi: 10.1093/sleep/zsaa084
24. Auger ML, Floresco SB. Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory. International Journal of Neuropsychopharmacology. 2014; 18(2). doi: 10.1093/ijnp/pyu013
25. Nuss P, Ferreri F, Bourin M. An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action. Neuropsychiatric Disease and Treatment. 2019; 15: 1781-1795. doi: 10.2147/ndt.s200568
26. Jung ME. A Protective Role of Translocator Protein in Alzheimer’s Disease Brain. Current Alzheimer Research. 2020; 17(1): 3-15. doi: 10.2174/1567205017666200217105950
27. Shang C, Yao RM, Guo Y, et al. Translocator protein–mediated fast-onset antidepressant-like and memory-enhancing effects in chronically stressed mice. Journal of Psychopharmacology. 2020; 34(4): 441-451. doi: 10.1177/0269881119896304
28. Zhang Z, Li Y, Jiang S, et al. Targeting CCL5 signaling attenuates neuroinflammation after seizure. CNS Neuroscience & Therapeutics. 2022; 29(1): 317-330. doi: 10.1111/cns.14006
29. Ajoy R, Lo YC, Ho MH, et al. CCL5 promotion of bioenergy metabolism is crucial for hippocampal synapse complex and memory formation. Molecular Psychiatry. 2021; 26(11): 6451-6468. doi: 10.1038/s41380-021-01103-3
30. Ni RJ, et al. Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain. Zoological Research. 2023; 44(3): 543-555. doi: 10.24272/j.issn.2095-8137.2022.389
31. Pettit NL, Yap EL, Greenberg ME, et al. Fos ensembles encode and shape stable spatial maps in the hippocampus. Nature. 2022; 609(7926): 327-334. doi: 10.1038/s41586-022-05113-1
32. Yap EL, Pettit NL, Davis CP, et al. Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network. Nature. 2020; 590(7844): 115-121. doi: 10.1038/s41586-020-3031-0
33. Shuken SR, Rutledge J, Iram T, et al. Limited proteolysis–mass spectrometry reveals aging-associated changes in cerebrospinal fluid protein abundances and structures. Nature Aging. 2022; 2(5): 379-388. doi: 10.1038/s43587-022-00196-x
34. Camilli C, Hoeh AE, De Rossi G, et al. LRG1: an emerging player in disease pathogenesis. Journal of Biomedical Science. 2022; 29(1). doi: 10.1186/s12929-022-00790-6
35. Zhang Z ang, Sun Y, Yuan Z, et al. Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory. Oxidative Medicine and Cellular Longevity. 2022; 2022: 1-14. doi: 10.1155/2022/4163188
36. Leandro GS, Evangelista AF, Lobo RR, et al. Changes in Expression Profiles Revealed by Transcriptomic Analysis in Peripheral Blood Mononuclear Cells of Alzheimer’s Disease Patients. Journal of Alzheimer’s Disease. 2018; 66(4): 1483-1495. doi: 10.3233/jad-170205
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