REBOKSETİN’İN DİYABETİK SIÇANLARDA BOZULMUŞ DAVRANIŞ PARAMETRELERİ ÜZERİNDEKİ YARARLI ETKİLERİ

Yıl 2023, , 20 - 38, 20.01.2023

Nazlı Turan Yücel , Ümmühan Kandemir , Umut İrfan Üçel , Özgür Devrim Can , Ümide Demir Özkay

https://doi.org/10.33483/jfpau.1149796

Öz

Amaç: Diyabetik hastalarda duygu-durum hastalıklarının ve kognitif bozukluk insidansının genel popülasyona oranla daha yüksek olduğu bilinmektedir. Bu çalışmada, klinikte antidepresan etkinliği için reçete edilen reboksetin’in sıçanlarda diyabet ile indüklenen davranışsal ve bilişsel değişiklikler üzerine etkinliğinin araştırılması amaçlanmıştır.

Gereç ve Yöntem: Sıçanlarda deneysel diyabet modeli 50 mg/kg tek doz streptozotosin enjeksiyonu (i.v.) ile oluşturulnuştur. Reboksetin tedavisine diyabetik komplikasyonların oluşması için 4 hafta beklendikten sonra başlanmıştır. Deney hayvanlarının depresyon ve anksiyete düzeyleri sırasıyla modifiye zorlu yüzme ve yükseltilmiş artı şekilli labirent testleri ile araştırılmış; kognitif performansları ise Morris su tankı ve pasif sakınma testleri ie değerlendirilmiştir. Hayvanlarının motor aktiviteleri de aktivite kafesi ve Rota-rod testleri ile incelenmiştir.

Sonuç ve Tartışma: Deneyler sonucunda, diyabetik sıçanların depresyon ve anksiyete düzeylerinin yükseldiği ve bilişsel performanslarının zayıfladığı belirlenmiştir. İki hafta süre ile uygulanan reboksetin tedavisi (8 ve 16 mg/kg) diyabetik sıçanların yüksek depresyon ve anksiyete düzeylerini azaltırken, zayıflamış olan bilişsel performanslarını kayda değer ölçüde güçlendirmiştir. Elde edilen bulgular reboksetin’in diyabete bağlı olarak ortaya çıkan davranışsal ve bilişsel bozuklukların tedavisinde terapötik bir potansiyele sahip olabileceğine işaret etmiştir.

Anahtar Kelimeler

Anksiyete, depresyon, Diabetes mellitus, kognisyon, reboksetin

Destekleyen Kurum

Anadolu Üniversitesi

Proje Numarası

Proje Numarası: 1809S307

Teşekkür

Bu araştırma, Anadolu Üniversitesi Bilimsel Araştırma Projeleri Komisyonu tarafından desteklenmiştir (Proje Numarası: 1809S307).

BENEFICIAL EFFECTS OF REBOXETINE ON IMPAIRED BEHAVIORAL PARAMETERS OF DIABETIC RATS

Öz

Objective: The incidence of emotional and cognitive disorders are higher in diabetic patients with respect to the general population. In this study, it was aimed to investigate the efficacy of reboxetine, a clinically prescribed drug for its antidepressant effect, on behavioral and cognitive alterations caused by diabetes in rats.

Material and Method: An experimental diabetes model in rats was induced with a single 50 mg/kg injection of streptozotocin (i.v.). Reboxetine treatment was started 4 weeks after induction of diabetes in order to observe diabetic complications. Depression and anxiety levels of experimental animals were investigated by modified forced swimming and elevated plus-maze tests, respectively; cognitive performances were evaluated by Morris water-maze and passive avoidance experiments. The motor activities of the animals were also examined with the activity cage and Rota-rod tests.

Result and Discussion: Obtained results indicated that the depression and anxiety levels of diabetic rats were increased and their cognitive performances were weakened. Reboxetine treatment (8 and 16 mg/kg) for two weeks reduced the elevated depression and anxiety levels in diabetic rats, while significantly improving their weakened cognitive performance. The findings indicated that reboxetine might possess a therapeutic potential for the cure of behavioral and cognitive impairements concomitant with diabetes.

Anahtar Kelimeler

Anxiety, cognition, depression, Diabetes mellitus, reboxetine

Proje Numarası

Proje Numarası: 1809S307

Kaynakça

• 1. American Diabetes Association (2012). Diagnosis and classification of diabetes mellitus. Diabetes Care, 35(1), 64–S71. [CrossRef]
• 2. Wolfsdorf, J., Glaser, N., Sperling, M.A. (2006). Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care, 29(5), 1150–1159. [CrossRef]
• 3. Venkatraman, R., Singhi, S.C. (2006). Hyperglycemic hyperosmolar nonketotic syndrome. Indian Journal of Pediatrics, 73(1), 55–60. [CrossRef]
• 4. Tripathi, B.K., Srivastava, A.K. (2006). Diabetes mellitus: Complications and therapeutics. International Medical Journal of Experimental and Clinical Research, 12(7), 130–147.
• 5. Forbes, J.M., Cooper, M.E. (2013). Mechanisms of diabetic complications. Physiological Reviews, 93(1), 137–188. [CrossRef]
• 6. Can, O.D., Öztürk, Y. (2009). Diabetes mellitus’un diğer yüzü: Psikiyatrik ve nörodejeneratif komplikasyonlar. Turkiye Klinikleri Journal of Medical Sciences, 29(4), 968-975.
• 7. Kovacs, M., Goldston, D., Obrosky, D.S., Bonar, L.K. (1997). Psychiatric disorders in youths with IDDM: Rates and risk factors. Diabetes Care, 20(1), 36–44. [CrossRef]
• 8. Pasquier, F., Boulogne, A., Leys, D., Fontaine, P. (2006). Diabetes mellitus and dementia. Diabetes & Metabolism, 32(5), 403–414. [CrossRef]
• 9. Yager, J.Y. (2002). Hypoglycemic injury to the immature brain. Clinics in Perinatology, 29(4), 651-674. [CrossRef]
• 10. Sima, A.A., Kamiya, H., Li, Z.G. (2004). Insulin, C-peptide, hyperglycemia, and central nervous system complications in diabetes. European Journal of Pharmacology, 490(1), 187–197. [CrossRef]
• 11. Ahmad, Q., Merali, Z. (1988). The spontaneously diabetic Wistar-BB rat manifests altered grooming and catalepsy responses: İmplications of impaired dopamine function. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 12(2), 291–298. [CrossRef]
• 12. Hilakivi-Clarke, L.A., Wozniak, K.M., Durcan, M.J., Linnoila, M. (1990). Behavior of streptozotocin-diabetic mice in tests of exploration, locomotion, anxiety, depression and aggression. Physiology & Behavior, 48(3), 429–433. [CrossRef]
• 13. Miyata, S., Hirano, S., Kamei, J. (2005). Abnormal benzodiazepine receptor function in the depressive-like behavior of diabetic mice. Pharmacology, Biochemistry, and Behavior, 82(4), 615–620. [CrossRef]
• 14. Kamal, A., Biessels, G.J., Duis, S.E., Gispen, W.H. (2000). Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: Interaction of diabetes and ageing. Diabetologia, 43(4), 500–506. [CrossRef]
• 15. Bannerman, D.M., Good, M.A., Butcher, S.P., Ramsay, M., Morris, R.G. (1995). Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature, 378(6553), 182–186. [CrossRef]
• 16. McCarthy, A.M., Lindgren, S., Mengeling, M.A., Tsalikian, E., Engvall, J.C. (2002). Effects of diabetes on learning in children. Pediatrics, 109(1), E9. [CrossRef]
• 17. Ryan, C.M., Geckle, M. (2000). Why is learning and memory dysfunction in Type 2 diabetes limited to older adults? Diabetes /Metabolism Research and Reviews, 16(5), 308–315. [CrossRef]
• 18. James, T., Kula, B., Choi, S., Khan, S.S., Bekar, L.K., Smith, N.A. (2021). Locus coeruleus in memory formation and Alzheimer's disease. The European Journal of Neuroscience, 54(8), 6948–6959. [CrossRef]
• 19. van Stegeren, A.H. (2008). The role of the noradrenergic system in emotional memory. Acta Psychologica, 127(3), 532–541. [CrossRef]
• 20. Hakamata, Y., Mizukami, S., Izawa, S., Okamura, H., Mihara, K., Marusak, H., Moriguchi, Y., Hori, H., Hanakawa, T., Inoue, Y., Tagaya, H. (2022). Implicit and explicit emotional memory recall in anxiety and depression: Role of basolateral amygdala and cortisol-norepinephrine interaction. Psychoneuroendocrinology, 136, 105598. [CrossRef]
• 21. Ferguson, J.M., Wesnes, K.A., Schwartz, G.E. (2003). Reboxetine versus paroxetine versus placebo: Effects on cognitive functioning in depressed patients. International Clinical Psychopharmacology, 18(1), 9–14. [CrossRef]
• 22. Warner, T.A., Drugan, R.C. (2012). Morris water maze performance deficit produced by intermittent swim stress is partially mediated by norepinephrine, Pharmacology, Biochemistry, and Behavior, 101, 24-34. [CrossRef]
• 23. Khanam, R., Pillai, K.K. (2005). Lack of hypo/hyperglycemic effects of reboxetine in diabetic and non-diabetic rats. Fundamental & Clinical Pharmacology, 19(6), 657–659. [CrossRef]
• 24. Turan Yücel, N., Can, Ö.D., Demir Özkay, Ü. (2020). Catecholaminergic and opioidergic system mediated effects of reboxetine on diabetic neuropathic pain. Psychopharmacology, 237(4), 1131–1145. [CrossRef]
• 25. Aydin, S., Ozkul, C., Yucel, N.T., Karaca, H. (2021). Gut microbiome alteration after Reboxetine administration in type-1 diabetic rats. Microorganisms, 9(9), 1948. [CrossRef]
• 26. Skalska, S., Kyselova, Z., Gajdosikova, A., Karasu, C., Stefek, M., Stolc, S. (2008). Protective effect of stobadine on NCV in streptozotocin-diabetic rats: Augmentation by vitamin E. General Physiology and Biophysics, 27(2), 106–114. [CrossRef]
• 27. Zaghloul, R.A., Abdelghany, A.M., Samra, Y.A. (2022). Rutin and selenium nanoparticles protected against STZ-induced diabetic nephropathy in rats through downregulating Jak-2/Stat3 pathway and upregulating Nrf-2/HO-1 pathway. European Journal of Pharmacology, 175289. [CrossRef]
• 28. Ramzani Ghara, A., Ezzati Ghadi, F., Hosseini, S.H., Piacente, S., Cerulli, A., Alizadeh, A., Mirmahmoudi, R. (2021). Antioxidant and antidiabetic effect of capparis decidua edgew (forssk.) extract on liver and pancreas of streptozotocin-induced diabetic rats. Journal of Applied Biotechnology Reports, 8(1), 76-82.
• 29. Üçel, U.İ., Can, Ö.D., Demir Özkay, Ü., Öztürk, Y. (2015). Antihyperalgesic and antiallodynic effects of mianserin on diabetic neuropathic pain: A study on mechanism of action. European Journal of Pharmacology, 756, 92–106. [CrossRef]
• 30. Scheuer, K., Rostock, A., Bartsch, R., Müller, W.E. (1999). Piracetam improves cognitive performance by restoring neurochemical deficits of the aged rat brain. Pharmacopsychiatry, 32(1), 10–16. [CrossRef]
• 31. Can, O.D., Oztürk, Y., Ozkay, U.D. (2011). Effects of insulin and St. John's Wort treatments on anxiety, locomotory activity, depression, and active learning parameters of streptozotocin-diabetic rats. Planta Medica, 77(18), 1970–1976. [CrossRef]
• 32. Spolidório, P.C., Echeverry, M.B., Iyomasa, M., Guimarães, F.S., Del Bel, E.A. (2007). Anxiolytic effects induced by inhibition of the nitric oxide-cGMP pathway in the rat dorsal hippocampus. Psychopharmacology, 195(2), 183–192. [CrossRef]
• 33. Cryan, J.F., Markou, A., Lucki, I. (2002). Assessing antidepressant activity in rodents: Recent developments and future needs. Trends in Pharmacological Sciences, 23(5), 238–245. [CrossRef]
• 34. Zanoli, P., Rivasi, M., Zavatti, M., Brusiani, F., Baraldi, M. (2005). New insight in the neuropharmacological activity of Humulus lupulus L. Journal of Ethnopharmacology, 102(1), 102–106. [CrossRef]
• 35. Can, Ö.D., Ulupınar, E., Özkay, Ü.D., Yegin, B., Öztürk, Y. (2012). The effect of simvastatin treatment on behavioral parameters, cognitive performance, and hippocampal morphology in rats fed a standard or a high-fat diet. Behavioural Pharmacology, 23(5-6), 582–592. [CrossRef]
• 36. Üçel, U.İ., Can, Ö.D., Demir Özkay, Ü., Ulupinar, E. (2020). Antiamnesic effects of tofisopam against scopolamine-induced cognitive impairments in rats. Pharmacology, Biochemistry, and Behavior, 190, 172858. [CrossRef]
• 37. Nagayach, A., Patro, N., Patro, I. (2014). Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Frontiers in Cellular Neuroscience, 8, 355. [CrossRef]
• 38. Trulson, M.E., Himmel, C.D. (1983). Decreased brain dopamine synthesis rate and increased [3H] spiroperidol binding in streptozotocin-diabetic rats. Journal of Neurochemistry, 40(5), 1456–1459. [CrossRef]
• 39. Shimizu, H., Shimomura, Y., Takahashi, M., Kobayashi, I., Kobayashi, S. (1990). Dopamine receptor in the streptozotocin-induced diabetic rats. Experimental and Clinical Endocrinology, 95(2), 263–266. [CrossRef]
• 40. Abbruzzese, G., Schenone, A., Scramuzza, G., Caponnetto, C., Gasparetto, B., Adezati, L., Abbruzzese, M., Viviani, G.L. (1993). Impairment of central motor conduction in diabetic patients. Electroencephalography and Clinical Neurophysiology, 89(5), 335–340. [CrossRef]
• 41. Porsolt, R.D., Le Pichon, M., Jalfre, M. (1977). Depression: A new animal model sensitive to antidepressant treatments. Nature, 266, 730–732. [CrossRef]
• 42. Tabatabaei, S., Ghaderi, S., Bahrami-Tapehebur, M., Farbood, Y., Rashno, M. (2017). Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin-induced diabetic rats. Biomedicine & Pharmacotherapy, 96, 279–290. [CrossRef]
• 43. Rahmani, G., Farajdokht, F., Mohaddes, G., Babri, S., Ebrahimi, V., Ebrahimi, H. (2020). Garlic (Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats. Archives of Physiology and Biochemistry, 126(2), 95–100. [CrossRef]
• 44. Bellush, L.L., Reid, S.G., North, D. (1991). The functional significance of biochemical alterations in streptozotocin-induced diabetes. Physiology & Behavior, 50(5), 973–981. [CrossRef]
• 45. Sumiyoshi, T., Ichikawa, J., Meltzer, H.Y. (1997). The effect of streptozotocin-induced diabetes on dopamine2, serotonin1A and serotonin2A receptors in the rat brain. Neuropsychopharmacology, 16(3), 183–190. [CrossRef]
• 46. Hirano, S., Miyata, S., Onodera, K., Kamei, J. (2006). Effects of histamine H(1) receptor antagonists on depressive-like behavior in diabetic mice. Pharmacology, Biochemistry, and Behavior, 83(2), 214–220. [CrossRef]
• 47. Kalueff, A., Nutt, D.J. (1996). Role of GABA in memory and anxiety. Depression and Anxiety, 4(3), 100–110. [CrossRef]
• 48. Adamec, R., Shallow, T. (2000). Effects of baseline anxiety on response to kindling of the right medial amygdala. Physiology & Behavior, 70(1-2), 67–80. [CrossRef]
• 49. Simon, P., Dupuis, R., Costentin, J. (1994). Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behavioural Brain Research, 61(1), 59–64. [CrossRef]
• 50. Gomez, R., Vargas, C.R., Wajner, M., Barros, H.M. (2003). Lower in vivo brain extracellular GABA concentration in diabetic rats during forced swimming. Brain Research, 968(2), 281–284. [CrossRef]
• 51. Figlewicz, D.P., Brot, M.D., McCall, A.L., Szot, P. (1996). Diabetes causes differential changes in CNS noradrenergic and dopaminergic neurons in the rat: A molecular study. Brain Research, 736(1-2), 54–60. [CrossRef]
• 52. Gotoh, M., Li, C., Yatoh, M., Okabayashi, N., Habu, S., Hirooka, Y. (2006). Hypothalamic monoamine metabolism is different between the diabetic GK (Goto-Kakizaki) rats and streptozotocin-induced diabetic rats. Brain Research, 1073-1074, 497–501. [CrossRef]
• 53. Gill, D.S., Thompson, C.S., Dandona, P. (1988). Increased histamine in plasma and tissues in diabetic rats. Diabetes Research, 7(1), 31–34. [CrossRef]
• 54. Chan, O., Inouye, K., Riddell, M.C., Vranic, M., Matthews, S.G. (2003). Diabetes and the hypothalamo-pituitary-adrenal (HPA) axis. Minerva Endocrinologica, 28(2), 87–102.
• 55. De Nicola, A.F., Fridman, O., Del Castillo, E.J., Foglia, V.G. (1976). The influence of streptozotocin diabetes on adrenal function in male rats. Hormone and Metabolic Research, 8(5), 388–392. [CrossRef]
• 56. Scribner, K.A., Walker, C.D., Cascio, C.S., Dallman, M.F. (1991). Chronic streptozotocin diabetes in rats facilitates the acute stress response without altering pituitary or adrenal responsiveness to secretagogues. Endocrinology, 129(1), 99–108. [CrossRef]
• 57. Lapmanee, S., Charoenphandhu, J., Charoenphandhu, N. (2013). Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors. Behavioural Brain Research, 250, 316–325. [CrossRef]
• 58. Stahl, S.M., Mendels, J., Schwartz, G.E. (2002). Effects of reboxetine on anxiety, agitation, and insomnia: Results of a pooled evaluation of randomized clinical trials. Journal of Clinical Psychopharmacology, 22(4), 388–392. [CrossRef]
• 59. Tashakori, A., Arabgol, F., Panaghi, L. (2007). Effect of reboxetine on reduction of anxiety symptoms in depressed children and adolescents. Jundıshapur Scientific Medical Journal, 6 (2), 210-218.
• 60. Gao, S., Zhang, X., Xu, H., Miao, D., Qian, J., Wu, Z., Shi, W. (2022). Promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine, a selective norepinephrine reuptake inhibitor. Behavioural Brain Research, 416, 113535. [CrossRef]
• 61. Młyniec, K., Nowak, G. (2015). Up-regulation of the GPR39 Zn2+-sensing receptor and CREB/BDNF/TrkB pathway after chronic but not acute antidepressant treatment in the frontal cortex of zinc-deficient mice. Pharmacological Reports, 67(6), 1135–1140. [CrossRef]
• 62. Gutiérrez, I.L., González-Prieto, M., Caso, J.R., García-Bueno, B., Leza, J.C., Madrigal, J. (2019). Reboxetine treatment reduces neuroinflammation and neurodegeneration in the 5xFAD mouse model of Alzheimer's disease: Role of CCL2. Molecular Neurobiology, 56(12), 8628–8642. [CrossRef]
• 63. Liu, P., Li, H., Wang, Y., Su, X., Li, Y., Yan, M., Ma, L., Che, H. (2020). Harmine ameliorates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway in STZ-induced diabetic rats. Frontiers in Pharmacology, 11, 535. [CrossRef]
• 64. Baluchnejadmojarad, T., Kiasalari, Z., Afshin-Majd, S., Ghasemi, Z., Roghani, M. (2017). S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase. European Journal of Pharmacology, 794, 69–76. [CrossRef]
• 65. Gardoni, F., Kamal, A., Bellone, C., Biessels, G.J., Ramakers, G.M., Cattabeni, F., Gispent, W.H., Di Luca, M. (2002). Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats. Journal of Neurochemistry, 80(3), 438–447. [CrossRef]
• 66. Lakhman, S.S., Kaur, G. (1994). Effect of alloxan-induced diabetes on acetylcholinesterase activity from discrete areas of rat brain. Neurochemistry International, 24(2), 159–163. [CrossRef]
• 67. Arrick, D.M., Sharpe, G.M., Sun, H., Mayhan, W.G. (2007). Diabetes-induced cerebrovascular dysfunction: Role of poly(ADP-ribose) polymerase. Microvascular Research, 73(1), 1–6. [CrossRef]
• 68. Martínez-Tellez, R., Gómez-Villalobos, M., Flores, G. (2005). Alteration in dendritic morphology of cortical neurons in rats with diabetes mellitus induced by streptozotocin. Brain Research, 1048(1-2), 108–115. [CrossRef]
• 69. Manschot, S.M., Biessels, G.J., Cameron, N.E., Cotter, M.A., Kamal, A., Kappelle, L.J., Gispen, W.H. (2003). Angiotensin converting enzyme inhibition partially prevents deficits in water maze performance, hippocampal synaptic plasticity and cerebral blood flow in streptozotocin-diabetic rats. Brain Research, 966(2), 274–282. [CrossRef]
• 70. Feltmann, K., Konradsson-Geuken, Å., De Bundel, D., Lindskog, M., Schilström, B. (2015). Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats. Behavioral Neuroscience, 129(6), 701–708. [CrossRef]
• 71. De Bundel, D., Femenía, T., DuPont, C.M., Konradsson-Geuken, Å., Feltmann, K., Schilström, B., Lindskog, M. (2013). Hippocampal and prefrontal dopamine D1/5 receptor involvement in the memory-enhancing effect of reboxetine. The International Journal of Neuropsychopharmacology, 16(9), 2041–2051. [CrossRef]
• 72. Barth, V., Need, A.B., Tzavara, E. T., Giros, B., Overshiner, C., Gleason, S.D., Wade, M., Johansson, A.M., Perry, K., Nomikos, G.G., Witkin, J.M. (2013). In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder. The Journal of Pharmacology and Experimental Therapeutics, 344(2), 501–510. [CrossRef]
• 73. Harmer, C.J., Hill, S.A., Taylor, M.J., Cowen, P.J., Goodwin, G.M. (2003). Toward a neuropsychological theory of antidepressant drug action: Increase in positive emotional bias after potentiation of norepinephrine activity. The American Journal of Psychiatry, 160(5), 990–992. [CrossRef]
• 74. Harmer, C.J., O'Sullivan, U., Favaron, E., Massey-Chase, R., Ayres, R., Reinecke, A., Goodwin, G.M., Cowen, P.J. (2009). Effect of acute antidepressant administration on negative affective bias in depressed patients. The American Journal of Psychiatry, 166(10), 1178–1184. [CrossRef]
• 75. Lee, J.H., Ji, S.H., Jung, J.Y., Lee, M.Y., Lee, C.K. (2021). High blood glucose levels affect auditory brainstem responses after acoustic overexposure in rats. Audiology & Neuro-otology, 26(4), 257–264. [CrossRef]
• 76. Wang, Y., Yang, Y., Liu, Y., Guo, A., Zhang, Y. (2022). Cognitive impairments in type 1 diabetes mellitus model mice are associated with synaptic protein disorders. Neuroscience Letters, 777, 136587. [CrossRef]
• 77. Parekh, P.K., Johnson, S.B., Liston, C. (2022). Synaptic mechanisms regulating mood state transitions in depression. Annual Review of Neuroscience, 45, 581–601. [CrossRef]
• 78. Lu, C., Wei, Z., Wang, Y., Li, S., Tong, L., Liu, X., Fan, B., Wang, F. (2022). Soy isoflavones alleviate lipopolysaccharide-induced depressive-like behavior by suppressing neuroinflammation, mediating tryptophan metabolism and promoting synaptic plasticity. Food & Function, 13(18), 9513–9522. [CrossRef]
• 79. Fan, X.X., Sun, W.Y., Li, Y., Tang, Q., Li, L.N., Yu, X., Wang, S.Y., Fan, A.R., Xu, X.Q., Chang, H.S. (2022). Honokiol improves depression-like behaviors in rats by HIF-1α- VEGF signaling pathway activation. Frontiers in Pharmacology, 13, 968124. [CrossRef]
• 80. Can, Ö.D., Üçel, U.İ., Demir Özkay, Ü., Ulupınar, E. (2018). The effect of agomelatine treatment on diabetes-induced cognitive impairments in rats: Concomitant alterations in the hippocampal neuron numbers. International Journal of Molecular Sciences, 19(8), 2461. [CrossRef]
• 81. Yuan, P., Zhang, J., Li, L., Song, Z. (2019). Fluoxetine attenuated anxiety-like behaviors in streptozotocin-induced diabetic mice by mitigating the inflammation. Mediators of Inflammation, 2019, 4315038. [CrossRef]
• 82. Beauquis, J., Roig, P., De Nicola, A.F., Saravia, F. (2009). Neuronal plasticity and antidepressants in the diabetic brain. Annals of the New York Academy of Sciences, 1153, 203–208. [CrossRef]
• 83. Herrera-Guzmán, I., Gudayol-Ferré, E., Herrera-Guzmán, D., Guàrdia-Olmos, J., Hinojosa-Calvo, E., Herrera-Abarca, J.E. (2009). Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder. Journal of Psychiatric Research, 43(9), 855–863. [CrossRef]