Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Comparing the effect of plasma therapy with estradiol valerate in motor and cognitive behavioral disorders in ovariectomized old rats: Behavioral, biochemical, and protein expression

Document Type : Original Article

Authors
1 Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2 2 Department of Medical Laboratory Science, Faculty of Medicine, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran
3 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4 Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract
Objective(s): This study investigated the effects of young plasma therapy (YPT) compared to estrogen therapy (E2T) on motor and cognitive impairments in aged ovariectomized (OVX) rats.
Materials and Methods: Sixty female Wistar rats were divided as follows: 1). 2-3 months control young group. Five 22-24 months old groups: 1) Control, 2) Sham, 3) OVX, 4) OVX.E2, and 5) OVX.YP. Young plasma (1 ml plasma, through the tail vein, 3 days weekly for 4 weeks) and E2 (30 mg/kg, SC, 5 days weekly for 4 weeks) were administrated to OVX rats. The open field, elevated plus maze, and Barne’s maze were used to assess the behaviors. Then, miR-134 and miR-124 (RT- RCR), SIRT1, CREB, and BDNF (western blot), and anti-oxidants/oxidants markers (Photometry) levels were assessed in the rat’s hippocampal tissues.
Results: OVX caused up-regulated hippocampal miR-134 and miR-124 expression levels (P<0.001) while down-regulated SIRT1, CREB, and BDNF protein expressions (P<0.001). Also, ovariectomy Increased TOS, OSI, and MDA (P<0.001) while decreasing TAC (P<0.001) compared to sham. Treatment with both E2T and YPT significantly improved all oxidative stress indexes (P<0.0.001) and increased p-CREB, BDNF, and SIRT1 protein levels (P<0.05, P<0.01) while decreasing the expression of miR-134 and miR-124 (P<0.001). 
Conclusion: YPT is a non-pharmacological therapeutic as much as or more than E-2T, which can exhibit anti-oxidative and anti-inflammatory potential in the hippocampal tissue and improve cognitive deficits in aged OVX rats without unknown side effects.
Keywords
Subjects

1. Diz-Chaves Y, Kwiatkowska-Naqvi A, Von Hülst H, Pernía O, Carrero P, Garcia-Segura LM. Behavioral effects of estradiol therapy in ovariectomized rats depend on the age when the treatment is initiated. Exp Gerontol 2012; 47:93-99.
2. Seo SY, Kang SY, Kwon OS, kyun Bang S, Kim SP, Choi K-H, et al. A mechanical acupuncture instrument mitigates the endoplasmic reticulum stress and oxidative stress of ovariectomized rats. Integr Med Res 2019; 8:187-194.
3. Renczés E, Borbélyová V, Steinhardt M, Höpfner T, Stehle T, Ostatníková D, et al. The role of estrogen in anxiety-like behavior and memory of middle-aged female rats. Front Endocrinol (Lausanne) 2020; 11:570560.
4. Luca M, Luca A, Calandra C. The role of oxidative damage in the pathogenesis and progression of Alzheimer’s disease and vascular dementia. Oxid Med Cell Longev 2015; 2015:504678.
5. Habibi P, Babri S, Ahmadiasl N, Yousefi H. Effects of genistein and swimming exercise on spatial memory and expression of microRNA 132, BDNF, and IGF-1 genes in the hippocampus of ovariectomized rats. Iran J Basic Med Sci 2017; 20:856-862.
6. Khaleghi M, Rajizadeh MA, Bashiri H, Kohlmeier KA, Mohammadi F, Khaksari M, et al. Estrogen attenuates physical and psychological stress‐induced cognitive impairments in ovariectomized rats. Brain Behav 2021; 11:e02139.
7. Marosi K, Felszeghy K, Mehra RD, Radák Z, Nyakas C. Are the neuroprotective effects of estradiol and physical exercise comparable during ageing in female rats? Biogerontology 2012; 13:413-427.
8. Cao Y, Yan Z, Zhou T, Wang G. SIRT1 regulates cognitive performance and ability of learning and memory in diabetic and nondiabetic models. J Diabetes Res 2017; 2017: 7121827.
9. Herskovits AZ, Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron 2014; 81:471-483.
10. Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Neurotrophic Factors 2014:223-250.
11. Rao YL, Ganaraja B, Murlimanju B, Joy T, Krishnamurthy A, Agrawal A. Hippocampus and its involvement in Alzheimer’s disease: A review. 3 Biotech 2022; 12:55-64.
12. Shen J, Xu L, Qu C, Sun H, Zhang J. Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro. Behav Brain Res 2018; 349:1-7.
13.Coolen M, Bally-Cuif L. MicroRNAs in brain development.  MicroRNA in Regenerative Medicine: Elsevier; 2015. p. 447-488.
14. Rashidi SK, Kalirad A, Rafie S, Behzad E, Dezfouli MA. The role of microRNAs in neurobiology and pathophysiology of the hippocampus. Front Mol Neurosci 2023; 16:1226413.
15. Eyileten C, Sharif L, Wicik Z, Jakubik D, Jarosz-Popek J, Soplinska A, et al. The relation of the brain-derived neurotrophic factor with microRNAs in neurodegenerative diseases and ischemic stroke. Molecular neurobiology 2021; 58:329-347.
16. Wang I-F, Ho P-C, Tsai K-J. MicroRNAs in learning and memory and their impact on Alzheimer’s disease. Biomedicines 2022; 10:1856.
17. Gao J, Wang W-Y, Mao Y-W, Gräff J, Guan J-S, Pan L, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 2010; 466:1105-1109.
18. Xu Y, Lai Y, Weng H, Tan L, Li Y, Chen G, et al. MiR-124 sensitizes cisplatin-induced cytotoxicity against CD133+ hepatocellular carcinoma cells by targeting SIRT1/ROS/JNK pathway. Aging (Albany NY) 2019; 11:2551.
19. Chulikhit Y, Sukhano W, Daodee S, Putalun W, Wongpradit R, Khamphukdee C, et al. Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on ovariectomy-induced cognitive impairment and oxidative stress in the mouse brain. Molecules 2021; 26:3442-3454.
20. Habibi P, Alihemmati A, Ahmadiasl N, Fateh A, Anvari E. Exercise training attenuates diabetes-induced cardiac injury through increasing miR-133a and improving pro-apoptosis/anti-apoptosis balance in ovariectomized rats. Iran J Basic Med Sci 2020; 23:79-85.
21. Eggel A, Wyss-Coray T. Parabiosis for the study of age-related chronic disease. Swiss Med Wkly 2014; 144:w13914.
22. Ashapkin VV, Kutueva LI, Vanyushin BF. The effects of parabiosis on aging and age-related diseases. Adv Exp Med Biol 2020;1260:107-122.
23. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014; 344:630-634.
24. Conese M, Carbone A, Beccia E, Angiolillo A. The fountain of youth: A tale of parabiosis, stem cells, and rejuvenation. Open Med 2017; 12:376-383.
25. Ximerakis M. Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types. Nat Aging 2023; 3: 327–345.
26. Castellano JM, Mosher KI, Abbey RJ, McBride AA, James ML, Berdnik D, et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature 2017; 544:488-492.
27. Zhao Y, Qian R, Zhang J, Liu F, Iqbal K, Dai C-L, et al. Young blood plasma reduces Alzheimer’s disease-like brain pathologies and ameliorates cognitive impairment in 3× Tg-AD mice. Alzheimers Res Ther 2020; 12:1-13.
28. Chen X, Luo Y, Zhu Q, Zhang J, Huang H, Kan Y, et al. Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism. Nat Aging 2024; 4: 814-838.
29. Habibi P, Alihemmatti A, Alipour M, Nourazar A, Yousefi H, Andalib S, et al. Effects of exercise on mir-29 and igf-1 expression and lipid profile in the heart of ovariectomized rat. Acta Endocrinol (Buchar) 2016; 12:130-136.
30. Babaei P, Mehdizadeh R, Ansar MM, Damirchi A. Effects of ovariectomy and estrogen replacement therapy on visceral adipose tissue and serum adiponectin levels in rats. Menopause int 2010; 16:100-104.
31. Liu A, Guo E, Yang J, Yang Y, Liu S, Jiang X, et al. Young plasma reverses age‐dependent alterations in hepatic function through the restoration of autophagy. Aging Cell 2018; 17:e12708.
32. Javani G, Alihemmati A, Habibi P, Yousefi H, Karimi P, Ebraheimi V, et al. The effects of genistein on renal oxidative stress and inflammation of ovariectomized rats. Jundishapur J Nat Pharm Prod 2019; 14:e57149.
33. Etaee F, Asadbegi M, Taslimi Z, Shahidi S, Sarihi A, Asl SS, et al. The effects of methamphetamine and buprenorphine, and their interaction on anxiety-like behavior and locomotion in male rats. Neurosci Lett 2017; 655:172-178.
34. Komaki A, Hashemi-Firouzi N, Shojaei S, Souri Z, Heidari S, Shahidi S. Study the effect of endocannabinoid system on rat behavior in elevated plus-maze. Basic Clin Neurosci 2015; 6:147-153.
35. Wu C, Yang L, Tucker D, Dong Y, Zhu L, Duan R, et al. Beneficial effects of exercise pretreatment in a sporadic Alzheimer’s rat model. Med Sci Sports Exerc 2018; 50:945-956.
36. Zhang J, Tucker LD, Lu Y, Yang L, Wu C, Li Y, et al. Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats. Neurochem Int 2018; 116:1-12.
37. Khajvand-Abedini M, Ziamajidi N, Nourian A, Bahmani M, Abbasalipourkabir R. Iron reduces the anti-inflammatory effect of omega-3 polyunsaturated fatty acids on the heart of STZ-and HFD-induced diabetic rats. Gene Rep 2021; 23:101079.
38. Mohammadi M, Abbasalipourkabir R, Ziamajidi N. Fish oil and chicoric acid combination protects better against palmitate-induced lipid accumulation via regulating AMPK-mediated SREBP-1/FAS and PPARα/UCP2 pathways. Arch Physiol Biochem 2023; 129:1-9.
39. Habibi P, Alihemmati A, NourAzar A, Yousefi H, Mortazavi S, Ahmadiasl N. Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats. Iran J Basic Med Sci 2016; 19:381-387.
40. Gasbarri A, Tavares MCH, Rodrigues RC, Tomaz C, Pompili A. Estrogen, cognitive functions and emotion: An overview on humans, non-human primates and rodents in reproductive years. Rev Neurosci 2012; 23:587-606.
41. Sharon JS, Deutsch GK, Tian L, Richardson K, Coburn M, Gaudioso JL, et al. Safety, tolerability, and feasibility of young plasma infusion in the plasma for Alzheimer symptom amelioration study: a randomized clinical trial. JAMA Neurol 2019; 76:35-40.
42. Berry A, Greco A, Giorgio M, Pelicci PG, De Kloet R, Alleva E, et al. Deletion of the lifespan determinant p66Shc improves performance in a spatial memory task, decreases levels of oxidative stress markers in the hippocampus and increases levels of the neurotrophin BDNF in adult mice. Exp Gerontol 2008; 43:200-208.
43. Roy RG, Mandal PK, Maroon JC. Oxidative stress occurs prior to amyloid Aβ plaque formation and tau phosphorylation in Alzheimer’s disease: Role of glutathione and metal ions. ACS Chem Neurosci 2023; 14:2944-2954.
44. Kiss T, Tarantini S, Csipo T, Balasubramanian P, Nyúl-Tóth Á, Yabluchanskiy A, et al. Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood. Geroscience 2020; 42:727-748.
45. Guo JM, Shu H, Wang L, Xu JJ, Niu XC, Zhang L. SIRT 1‐dependent AMPK pathway in the protection of estrogen against ischemic brain injury. CNS Neurosci Ther 2017; 23:360-369.
46. Wu T, Chen L, Zhou L, Xu J, Guo K. Platelets transport β-amyloid from the peripheral blood into the brain by destroying the blood-brain barrier to accelerate the process of Alzheimer’s disease in mouse models. Aging (Albany NY) 2021; 13:7644-7659.
47. Gandy S, Duff K. Post-menopausal estrogen deprivation and Alzheimer’s disease. Exp Gerontol 2000; 35:503-511.
48. McKinney BC, Lin C-W, Oh H, Tseng GC, Lewis DA, Sibille E. Hypermethylation of BDNF and SST genes in the orbital frontal cortex of older individuals: A putative mechanism for declining gene expression with age. Neuropsychopharmacology 2015; 40:2604-2613.
49. Scudellari M. Blood to blood. Nature 2015; 517:426-429.