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High-Salt Diet Differentially Affects Anxiety-Depression-Like Behaviours and Cognitive Functions in Mice: Gender Difference

Year 2024, Volume: 3 Issue: 1, 1 - 9, 23.07.2024

Abstract

Objective: Salt is a compound used for taste and flavor in the daily diet. Although the World Health Organization (WHO) recommends salt consumption below 5g/day, the average worldwide is 15.24g. A high salt diet (HSD) causes cognitive impairment by increasing oxidative stress and inflammation. This study aimed to determine the effect of HSD on anxiety-depression-like behaviors and cognitive functions in female and male mice.
Materials and Methods: Twenty-eight mice (14 females, 14 males) were divided into four groups depending on gender (n=7): Male Control, Male HSD, Female Control, and Female HSD. Mice were fed an HSD for 16 days. Open-field (OFT), tail-suspension (TST), forced swimming (FST), and novel object recognition (NORT) tests were used. In addition, biochemical and histopathological analyses were made from brain tissues.
Results: Compared to their control in females with HSD, the time spent in the center (p<0.01) and the number of rearing (p<0.01) decreased in the OFT. Also, an increase in sedentary time in the TST (p=0.027) and; a decreased memory index (p<0.01) in the NORT, were determined. There was no difference in all tests in males with HSD compared to their control group. Oxidative stress increased in both genders (male: p=0.021, female: p<0.001) but was higher in females. Inflammation was increased in both genders. The damage to the brain region was increased in both genders, and this increase was more in females.
Conclusions: HSD affects female mice more through the cumulative effect of oxidative stress and inflammation, increasing depression and anxiety, and decreasing memory index.

References

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  • 2. Patel Y, Joseph J. Sodium ıntake and heart failure. Int J Mol Sci. 2020; 21(24): 9474.
  • 3. Li Y, Lyu Y, Huang J, Huang K, Yu J. Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice. BMC Gastroenterol. 2021; 21(1): 335.
  • 4. Stern N, Buch A, Goldsmith R, Nitsan L, Margaliot M, Endevelt R, et al. The role of caloric intake in the association of high salt intake with high blood pressure. Sci Rep. 2021; 11(1): 15803.
  • 5. Wang Z, Cheng C, Yang X, Zhang C. L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4. PLoS One. 2021; 16(4): e0250126.
  • 6. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012; 380(9859): 2224-60.
  • 7. WHO global report on sodium intake reduction. Geneva: World Health Organization; 2023. Available from: https://www.who.int/publications/i/item/9789240069985. Retrieved; 13 Dec 2023
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  • 9. Wang Y, Liu X, Zhang C, Wang Z. High salt diet induces metabolic alterations in multiple biological processes of dahl salt-sensitive rats. J Nutr Biochem. 2018; 56: 133-141.
  • 10. Du X, Yu L, Ling S, Xie J, Chen W. High-salt diet ımpairs the neurons plasticity and the neurotransmitters-related biological processes. Nutrients. 2021; 13(11): 4123.
  • 11. Husain I, Akhtar M, Madaan T, Vohora D, Abdin MZ, Islamuddin M, et al. Tannins enriched fraction of emblica officinalis fruits alleviates high-salt and cholesterol diet-ınduced cognitive impairment in rats via Nrf2-ARE pathway. Front Pharmacol. 2018; 9: 23.
  • 12. Husain I, Akhtar M, Madaan T, Abdin MZ, Islamuddin M, Najmi AK. Rosuvastatin alleviates high-salt and cholesterol diet-induced cognitive impairment in rats via Nrf2-ARE pathway. Redox Rep. 2018; 23(1): 168-179.
  • 13. Santisteban MM, Iadecola C. Hypertension, dietary salt and cognitive impairment. J Cereb Blood Flow Metab. 2018; 38(12): 2112-28.
  • 14. Mogi M, Tsukuda K, Li JM, Iwanami J, Min LJ, Sakata A, et al. Inhibition of cognitive decline in mice fed a high-salt and cholesterol diet by the angiotensin receptor blocker, olmesartan. Neuropharmacology. 2007; 53(8): 899-905.
  • 15. Gilman TL, George CM, Andrade MA, Mitchell NC, Toney GM, Daws LC. High salt intake lowers behavioral inhibition. Front Behav Neurosci. 2019; 13: 271.
  • 16. Milte CM, Ball K, Crawford D, McNaughton SA. Diet quality and cognitive function in mid-aged and older men and women. BMC Geriatr 2019;19(1):361.
  • 17. Ge Q, Wang Z, Wu Y, Huo Q, Qian Z, Tian Z, et al. High salt diet impairs memory-related synaptic plasticity via increased oxidative stress and suppressed synaptic protein expression. Mol Nutr Food Res. 2017; 61(10): 1700134.
  • 18. Gohar EY, De Miguel C, Obi IE, Daugherty EM, Hyndman KA, Becker BK, et al. Acclimation to a high-salt diet is sex dependent. J Am Heart Assoc. 2022; 11(5): e020450.
  • 19. He W, Xu J, Mu R, Li Q, Lv DL, Huang Z, et al. High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation. Nat Commun. 2020; 11(1): 1732.
  • 20. Sun J, Li H, Jin Y, Yu J, Mao S, Su KP, et al. Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of parkinson's disease via gut microbiota-GLP-1 pathway. Brain Behav Immun. 2021; 91: 703-715.
  • 21. Koek W, Sandoval TL, Daws LC. Effects of the antidepressants desipramine and fluvoxamine on latency to immobility and duration of immobility in the forced swim test in adult male C57BL/6J mice. Behav Pharmacol. 2018; 29(5): 453-456.
  • 22. Dang R, Wang M, Li X, Wang H, Liu L, Wu Q, et al. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway. J Neuroinflammation. 2022; 19(1): 41.
  • 23. Cechella JL, Leite MR, Rosario AR, Sampaio TB, Zeni G. Diphenyl diselenide-supplemented diet and swimming exercise enhance novel object recognition memory in old rats. Age (Dordr). 2014; 36(4): 9666.
  • 24. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004; 37(2): 112-119.
  • 25. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38(12): 1103-1111.
  • 26. Zeren S, Bayhan Z, Kocak FE, Kocak C, Akcılar R, Bayat Z, et al. Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid-induced gastric ulcer in rats. J Surg Res. 2016; 203(2): 348-359.
  • 27. Rizvi ZA, Dalal R, Sadhu S, Kumar Y, Kumar S, Gupta SK, et al. High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity. Sci Adv. 2021; 7(37): eabg5016.
  • 28. Akcılar R, Akçer S, Şimşek H, Akcılar A, Bayat Z, Genç O. The effect of ozone on blood pressure in DOCA-salt-induced hypertensive rats. Int J Clin Exp Med 2015;8(8):12783-12791.
  • 29. Li Z, Hu L, Rong X, Luo J, Xu X, Zhao Y. Role of no table salt on hypertension and stroke based on large sample size from national health and nutrition examination survey database. BMC Public Health. 2022; 22(1): 1292.
  • 30. Arsang-Jang S, Mansourian M, Mohammadifard N, Khosravi A, Oveis-Gharan S, Nouri F, et al. Temporal trend analysis of stroke and salt intake: a 15-year population-based study. Nutr Neurosci. 2021; 24(5): 384-394.
  • 31. McKenzie, B., Santos, J. A., Trieu, K., Thout, S. R., Johnson, C., Arcand, J., ... & McLean, R. (2018). The Science of Salt: a focused review on salt‐related knowledge, attitudes and behaviors, and gender differences. The Journal of Clinical Hypertension, 20(5), 850-866.
  • 32. Hu L, Zhu S, Peng X, Li K, Peng W, Zhong Y, et al. High salt elicits brain ınflammation and cognitive dysfunction, accompanied by alternations in the gut microbiota and decreased SCFA production. J Alzheimers Dis. 2020; 77(2): 629-640.
  • 33. Nowak KL, Fried L, Jovanovich A, Ix J, Yaffe K, You Z, Chonchol M. Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices. Am J Nephrol 2018;47(1):57-65.
  • 34. Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, et al. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018; 21(2): 240-249.
  • 35. Costa AP, de Paula RC, Carvalho GF, Araújo JP, Andrade JM, de Almeida OL, de Faria EC, Freitas WM, Coelho OR, Ramires JA, Quinaglia e Silva JC, Sposito AC; Brasilia Heart Study Group. High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction. Atherosclerosis 2012;222(1):284-91.
  • 36. Kocak C, Kocak FE, Akcilar R, Isiklar OO, Kocak H, Bayat Z, Simsek H, Taser F, Altuntas I. Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life Sci 2016; 147:15-23.
  • 37. Ileriturk M, Kandemir O, Akaras N, Simsek H, Genc A, Kandemir FM. Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress. Reprod Toxicol. 2023; 118:108369.
  • 38. Liu YZ, Chen JK, Li ZP, Zhao T, Ni M, Li DJ, et al. High-salt diet enhances hippocampal oxidative stress and cognitive impairment in mice. Neurobiol Learn Mem. 2014; 114: 10-15.
  • 39. Akcılar R, Akcılar A, Şimşek H, Koçak FE, Koçak C, Yümün G, Bayat Z. Hyperbaric oxygen treatment ameliorates lung injury in paraquat intoxicated rats. Int J Clin Exp Pathol. 2015;8(10):13034-13042.
  • 40. Liu F, Mu J, Yuan Z, Wu G, Liu E, Zheng S, et al. High salt intake fails to enhance plasma adiponectin in normotensive salt-sensitive subjects. Nutrition. 2012; 28(4): 422-425.
  • 41. Şimşek H, Küçükler S, Gür C, Akaras N, Kandemir FM. Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: a multi-biomarker approach. Environ Sci Pollut Res Int 2023;30(45):101208-101222.
  • 42. Şimşek H, Akaras N, Gür C, Küçükler S, Kandemir FM. Beneficial effects of chrysin on cadmium-induced nephrotoxicity in rats: modulating the levels of Nrf2/HO-1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene. 2023; 875: 147502.
  • 43. Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol. 2020; 138: 111190.
  • 44. Simsek H, Akaras N. Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis. Int J Med Biochem. 2023; 6(2): 96-103.
  • 45. Şimşek H, Küçükler S, Gür C, İleritürk M, Aygörmez S, Kandemir F.M. Protective effects of zingerone against sodium arsenite-induced lung toxicity: A multi-biomarker approach. Iran J Basic Med Sci. 2023; 26(9): 1098-1106.
Year 2024, Volume: 3 Issue: 1, 1 - 9, 23.07.2024

Abstract

References

  • 1. Leal PEPT, da Silva AA, Rocha-Gomes A, Riul TR, Cunha RA, Reichetzeder C, et al. High-salt diet in the pre- and postweaning periods leads to amygdala oxidative stress and changes in locomotion and anxiety-like behaviors of male wistar rats. Front Behav Neurosci. 2022; 15: 779080.
  • 2. Patel Y, Joseph J. Sodium ıntake and heart failure. Int J Mol Sci. 2020; 21(24): 9474.
  • 3. Li Y, Lyu Y, Huang J, Huang K, Yu J. Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice. BMC Gastroenterol. 2021; 21(1): 335.
  • 4. Stern N, Buch A, Goldsmith R, Nitsan L, Margaliot M, Endevelt R, et al. The role of caloric intake in the association of high salt intake with high blood pressure. Sci Rep. 2021; 11(1): 15803.
  • 5. Wang Z, Cheng C, Yang X, Zhang C. L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4. PLoS One. 2021; 16(4): e0250126.
  • 6. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012; 380(9859): 2224-60.
  • 7. WHO global report on sodium intake reduction. Geneva: World Health Organization; 2023. Available from: https://www.who.int/publications/i/item/9789240069985. Retrieved; 13 Dec 2023
  • 8. Salt reduction: World Health Organization; 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/salt-reduction. Retrieved; 13 Dec 2023
  • 9. Wang Y, Liu X, Zhang C, Wang Z. High salt diet induces metabolic alterations in multiple biological processes of dahl salt-sensitive rats. J Nutr Biochem. 2018; 56: 133-141.
  • 10. Du X, Yu L, Ling S, Xie J, Chen W. High-salt diet ımpairs the neurons plasticity and the neurotransmitters-related biological processes. Nutrients. 2021; 13(11): 4123.
  • 11. Husain I, Akhtar M, Madaan T, Vohora D, Abdin MZ, Islamuddin M, et al. Tannins enriched fraction of emblica officinalis fruits alleviates high-salt and cholesterol diet-ınduced cognitive impairment in rats via Nrf2-ARE pathway. Front Pharmacol. 2018; 9: 23.
  • 12. Husain I, Akhtar M, Madaan T, Abdin MZ, Islamuddin M, Najmi AK. Rosuvastatin alleviates high-salt and cholesterol diet-induced cognitive impairment in rats via Nrf2-ARE pathway. Redox Rep. 2018; 23(1): 168-179.
  • 13. Santisteban MM, Iadecola C. Hypertension, dietary salt and cognitive impairment. J Cereb Blood Flow Metab. 2018; 38(12): 2112-28.
  • 14. Mogi M, Tsukuda K, Li JM, Iwanami J, Min LJ, Sakata A, et al. Inhibition of cognitive decline in mice fed a high-salt and cholesterol diet by the angiotensin receptor blocker, olmesartan. Neuropharmacology. 2007; 53(8): 899-905.
  • 15. Gilman TL, George CM, Andrade MA, Mitchell NC, Toney GM, Daws LC. High salt intake lowers behavioral inhibition. Front Behav Neurosci. 2019; 13: 271.
  • 16. Milte CM, Ball K, Crawford D, McNaughton SA. Diet quality and cognitive function in mid-aged and older men and women. BMC Geriatr 2019;19(1):361.
  • 17. Ge Q, Wang Z, Wu Y, Huo Q, Qian Z, Tian Z, et al. High salt diet impairs memory-related synaptic plasticity via increased oxidative stress and suppressed synaptic protein expression. Mol Nutr Food Res. 2017; 61(10): 1700134.
  • 18. Gohar EY, De Miguel C, Obi IE, Daugherty EM, Hyndman KA, Becker BK, et al. Acclimation to a high-salt diet is sex dependent. J Am Heart Assoc. 2022; 11(5): e020450.
  • 19. He W, Xu J, Mu R, Li Q, Lv DL, Huang Z, et al. High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation. Nat Commun. 2020; 11(1): 1732.
  • 20. Sun J, Li H, Jin Y, Yu J, Mao S, Su KP, et al. Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of parkinson's disease via gut microbiota-GLP-1 pathway. Brain Behav Immun. 2021; 91: 703-715.
  • 21. Koek W, Sandoval TL, Daws LC. Effects of the antidepressants desipramine and fluvoxamine on latency to immobility and duration of immobility in the forced swim test in adult male C57BL/6J mice. Behav Pharmacol. 2018; 29(5): 453-456.
  • 22. Dang R, Wang M, Li X, Wang H, Liu L, Wu Q, et al. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway. J Neuroinflammation. 2022; 19(1): 41.
  • 23. Cechella JL, Leite MR, Rosario AR, Sampaio TB, Zeni G. Diphenyl diselenide-supplemented diet and swimming exercise enhance novel object recognition memory in old rats. Age (Dordr). 2014; 36(4): 9666.
  • 24. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004; 37(2): 112-119.
  • 25. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38(12): 1103-1111.
  • 26. Zeren S, Bayhan Z, Kocak FE, Kocak C, Akcılar R, Bayat Z, et al. Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid-induced gastric ulcer in rats. J Surg Res. 2016; 203(2): 348-359.
  • 27. Rizvi ZA, Dalal R, Sadhu S, Kumar Y, Kumar S, Gupta SK, et al. High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity. Sci Adv. 2021; 7(37): eabg5016.
  • 28. Akcılar R, Akçer S, Şimşek H, Akcılar A, Bayat Z, Genç O. The effect of ozone on blood pressure in DOCA-salt-induced hypertensive rats. Int J Clin Exp Med 2015;8(8):12783-12791.
  • 29. Li Z, Hu L, Rong X, Luo J, Xu X, Zhao Y. Role of no table salt on hypertension and stroke based on large sample size from national health and nutrition examination survey database. BMC Public Health. 2022; 22(1): 1292.
  • 30. Arsang-Jang S, Mansourian M, Mohammadifard N, Khosravi A, Oveis-Gharan S, Nouri F, et al. Temporal trend analysis of stroke and salt intake: a 15-year population-based study. Nutr Neurosci. 2021; 24(5): 384-394.
  • 31. McKenzie, B., Santos, J. A., Trieu, K., Thout, S. R., Johnson, C., Arcand, J., ... & McLean, R. (2018). The Science of Salt: a focused review on salt‐related knowledge, attitudes and behaviors, and gender differences. The Journal of Clinical Hypertension, 20(5), 850-866.
  • 32. Hu L, Zhu S, Peng X, Li K, Peng W, Zhong Y, et al. High salt elicits brain ınflammation and cognitive dysfunction, accompanied by alternations in the gut microbiota and decreased SCFA production. J Alzheimers Dis. 2020; 77(2): 629-640.
  • 33. Nowak KL, Fried L, Jovanovich A, Ix J, Yaffe K, You Z, Chonchol M. Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices. Am J Nephrol 2018;47(1):57-65.
  • 34. Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, et al. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018; 21(2): 240-249.
  • 35. Costa AP, de Paula RC, Carvalho GF, Araújo JP, Andrade JM, de Almeida OL, de Faria EC, Freitas WM, Coelho OR, Ramires JA, Quinaglia e Silva JC, Sposito AC; Brasilia Heart Study Group. High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction. Atherosclerosis 2012;222(1):284-91.
  • 36. Kocak C, Kocak FE, Akcilar R, Isiklar OO, Kocak H, Bayat Z, Simsek H, Taser F, Altuntas I. Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life Sci 2016; 147:15-23.
  • 37. Ileriturk M, Kandemir O, Akaras N, Simsek H, Genc A, Kandemir FM. Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress. Reprod Toxicol. 2023; 118:108369.
  • 38. Liu YZ, Chen JK, Li ZP, Zhao T, Ni M, Li DJ, et al. High-salt diet enhances hippocampal oxidative stress and cognitive impairment in mice. Neurobiol Learn Mem. 2014; 114: 10-15.
  • 39. Akcılar R, Akcılar A, Şimşek H, Koçak FE, Koçak C, Yümün G, Bayat Z. Hyperbaric oxygen treatment ameliorates lung injury in paraquat intoxicated rats. Int J Clin Exp Pathol. 2015;8(10):13034-13042.
  • 40. Liu F, Mu J, Yuan Z, Wu G, Liu E, Zheng S, et al. High salt intake fails to enhance plasma adiponectin in normotensive salt-sensitive subjects. Nutrition. 2012; 28(4): 422-425.
  • 41. Şimşek H, Küçükler S, Gür C, Akaras N, Kandemir FM. Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: a multi-biomarker approach. Environ Sci Pollut Res Int 2023;30(45):101208-101222.
  • 42. Şimşek H, Akaras N, Gür C, Küçükler S, Kandemir FM. Beneficial effects of chrysin on cadmium-induced nephrotoxicity in rats: modulating the levels of Nrf2/HO-1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene. 2023; 875: 147502.
  • 43. Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol. 2020; 138: 111190.
  • 44. Simsek H, Akaras N. Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis. Int J Med Biochem. 2023; 6(2): 96-103.
  • 45. Şimşek H, Küçükler S, Gür C, İleritürk M, Aygörmez S, Kandemir F.M. Protective effects of zingerone against sodium arsenite-induced lung toxicity: A multi-biomarker approach. Iran J Basic Med Sci. 2023; 26(9): 1098-1106.
There are 45 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Article[En]
Authors

Hasan Şimşek 0000-0001-5573-4923

Mehmet Öz 0000-0003-4167-2623

Nurhan Akaras 0000-0002-8457-9448

Publication Date July 23, 2024
Submission Date November 27, 2023
Acceptance Date December 26, 2023
Published in Issue Year 2024 Volume: 3 Issue: 1

Cite

APA Şimşek, H., Öz, M., & Akaras, N. (2024). High-Salt Diet Differentially Affects Anxiety-Depression-Like Behaviours and Cognitive Functions in Mice: Gender Difference. Eurasian Journal of Molecular and Biochemical Sciences, 3(1), 1-9.