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Metabolic Brain Disease

Erschienen in:

03.05.2023 | Original Article

Buckwheat tartary regulates the Gsk-3β/β-catenin pathway to prevent neurobehavioral impairments in a rat model of surgical menopause

verfasst von: Anil Kumar Rana, Supriya Sharma, Rajneesh Kumar, Damanpreet Singh

Erschienen in: Metabolic Brain Disease | Ausgabe 6/2023

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Abstract

Menopause is a natural aging process characterized by decreased levels of sex hormones in females. Deprivation of estrogen following menopause results in alterations of dendritic arborization of the neuron that leads to neurobehavioral complications. Hormone replacement therapy is in practice to manage postmenopausal conditions but is associated with a lot of adverse effects. In the present study, the efficacy of buckwheat tartary (Fagopyrum tataricum) whole seed extract was investigated against the neurobehavioral complication in middle-aged ovariectomized rats, which mimic the clinical postmenopausal condition. Hydroalcoholic extraction (80% ethanol) was done, and quantification of major marker compounds in the extract was performed using HPLC. Oral treatment of the extract following the critical window period rescued the reconsolidation process of spatial and recognition memory, as well as depression-like behavior. Gene expression analysis disclosed elevated oxidative stress and neuroinflammation that largely disturb the integrity of the blood-brain barrier in ovariectomized rats. Gfap and Pparγ expression also showed reactive astrogliosis in the rats subjected to ovariectomy. The extract treatment reverted the elevated oxidative stress, neuroinflammation and expression of the studied genes. Furthermore, protein expression analysis revealed that Gsk-3β was activated differentially in the brain, as suggested by β-catenin protein expression, which was normalized following the treatment with extract and rescued the altered neurobehavioral process. The results of the current study concluded that Fagopyrum tataricum seed extract is better option to overcome the neurobehavioral complications associated with the menopause.

Aggarwal A, Sharma N, Khera A, Sandhir R, Rishi V (2020) Quercetin alleviates cognitive decline in ovariectomized mice by potentially modulating histone acetylation homeostasis. J Nutr Biochem 84:108439. https://doi.org/10.1016/j.jnutbio.2020.108439CrossRefPubMed

Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 1863:585–597. https://doi.org/10.1016/j.biopha.2018.10.086CrossRefPubMed

Amer DA, Jähne M, Weigt C, Kretzschmar G, Vollmer G (2012) Effect of 17β-estradiol and flavonoids on the regulation of expression of newly identified oestrogen responsive genes in a rat raphe nuclei‐derived cell line. J Cell Physiol 227:3434–3445. https://doi.org/10.1002/jcp.24044CrossRefPubMed

Arevalo MA, Santos-Galindo M, Acaz-Fonseca E, Azcoitia I, Garcia-Segura LM (2013) Gonadal hormones and the control of reactive gliosis. Horm Behav 63:216–221. https://doi.org/10.1016/j.yhbeh.2012.02.021CrossRefPubMed

Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I, Ahmed J, Shahid M (2019) Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders. Front Aging Neurosci 11:155. https://doi.org/10.3389/fnagi.2019.00155CrossRefPubMedPubMedCentral

Bake S, Sohrabji F (2004) 17β-Estradiol differentially regulates blood-brain barrier permeability in young and aging female rats. Endocrinology 145:5471–5475. https://doi.org/10.1210/en.2004-0984CrossRefPubMed

Bakoyiannis I, Daskalopoulou A, Pergialiotis V, Perrea D (2019) Phytochemicals and cognitive health: are flavonoids doing the trick? Biomed Pharmacother 109:1488–1497. https://doi.org/10.1016/j.biopha.2018.10.086CrossRefPubMed

Barron H, Hafizi S, Andreazza AC, Mizrahi R (2017) Neuroinflammation and oxidative stress in psychosis and psychosis risk. Int J Mol Sci 18:651. https://doi.org/10.3390/ijms18030651CrossRefPubMedPubMedCentral

Beekmann K, Rubió L, de Haan LH, Actis-Goretta L, van der Burg B, van Bladeren PJ, Rietjens IM (2015) The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-γ). Food Funct 6:1098–1107. https://doi.org/10.1039/C5FO00076ACrossRefPubMed

Bjarnason NH (2005) Endometrial cancer and hormone-replacement therapy. The Lancet 366:200–201. https://doi.org/10.1016/S0140-6736(05)66901-2CrossRef

Borras C, Ferrando M, Inglés M, Gambini J, Lopez-Grueso R, Edo R, Mas-Bargues C, Pellicer A, Viña J (2021) Estrogen replacement therapy induces antioxidant and longevity-related genes in women after medically induced menopause. Oxid Med Cell Longev 2021. https://doi.org/10.1155%2F2021%2F8101615

Chekalina N, Burmak Y, Petrov Y, Borisova Z, Manusha Y, Kazakov Y, Kaidashev I (2018) Quercetin reduces the transcriptional activity of NF-kB in stable coronary artery disease. Indian Heart J 70:593–597. https://doi.org/10.1016/j.ihj.2018.04.006CrossRefPubMedPubMedCentral

Chen X, Liu Y, Zhu J, Lei S, Dong Y, Li L, Jiang B, Tan L, Wu J, Yu S, Zhao Y (2016) GSK-3β downregulates Nrf2 in cultured cortical neurons and in a rat model of cerebral ischemia-reperfusion. Sci Rep 6:1–6. https://doi.org/10.1038/srep20196CrossRef

Chen Y, Qin C, Huang J, Tang X, Liu C, Huang K, Xu J, Guo G, Tong A, Zhou L (2020) The role of astrocytes in oxidative stress of central nervous system: a mixed blessing. Cell Prolif 53:e12781. https://doi.org/10.1111/cpr.12781CrossRefPubMedPubMedCentral

Choi JY, Cho EJ, Lee HS, Lee JM, Yoon YH, Lee S (2013) Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model. Food Chem Toxicol 53:105–111. https://doi.org/10.1016/j.fct.2012.11.002CrossRefPubMed

Conde DM, Verdade RC, Valadares AL, Mella LF, Pedro AO, Costa-Paiva L (2021) Menopause and cognitive impairment: a narrative review of current knowledge. World J Psychiatry 11:412. https://doi.org/10.5498%2Fwjp.v11.i8.412CrossRefPubMedPubMedCentral

Daniel JM, Bohacek J (2010) The critical period hypothesis of estrogen effects on cognition: insights from basic research. Biochim Biophys Acta Bioenerg 1800:1068–1076. https://doi.org/10.1016/j.bbagen.2010.01.007CrossRef

de Andrade Teles RB, Diniz TC, Costa Pinto TC, de Oliveira Junior RG, Gama e Silva M, de Lavor ÉM, Fernandes AW, de Oliveira AP, de Almeida Ribeiro FP, da Silva AA, Cavalcante TC (2018) Flavonoids as therapeutic agents in Alzheimer’s and Parkinson’s diseases: A systematic review of preclinical evidences. Oxid Med Cell Longev 2018. https://doi.org/10.1155/2018/7043213

Ding F, Yao J, Zhao L, Mao Z, Chen S, Brinton RD (2013) Ovariectomy induces a shift in fuel availability and metabolism in the hippocampus of the female transgenic model of familial Alzheimer’s. PLoS ONE 8:e59825. https://doi.org/10.1371/journal.pone.0059825CrossRefPubMedPubMedCentral

Drolet J, Buchner-Duby B, Stykel MG, Coackley C, Kang JX, Ma DW, Ryan SD (2021) Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth. Mol Biol Cell 32:511–520. https://doi.org/10.1091/mbc.E20-09-0599CrossRefPubMedPubMedCentral

Ferensztajn-Rochowiak E, Tarnowski M, Samochowiec J, Michalak M, Ratajczak MZ, Rybakowski JK (2016) Increased mRNA expression of peripheral glial cell markers in bipolar disorder: the effect of long-term lithium treatment. Eur Neuropsychopharmacol 26:1516–1521. https://doi.org/10.1016/j.euroneuro.2016.07.009CrossRefPubMed

Gava G, Orsili I, Alvisi S, Mancini I, Seracchioli R, Meriggiola MC (2019) Cognition, mood and sleep in menopausal transition: the role of menopause hormone therapy. Medicina 55:668. https://doi.org/10.3390/medicina55100668CrossRefPubMedPubMedCentral

Gomes A, Fernandes E, Lima JL, Mira L, Corvo ML (2008) Molecular mechanisms of anti-inflammatory activity mediated by flavonoids. Curr Med Chem 15:1586–1605. https://doi.org/10.2174/092986708784911579CrossRefPubMed

Hara Y, Waters EM, McEwen BS, Morrison JH (2015) Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol Rev 95:785–807. https://doi.org/10.1152/physrev.00036.2014CrossRefPubMedPubMedCentral

Iglesias J, Morales L, Barreto GE (2017) Metabolic and inflammatory adaptation of reactive astrocytes: role of PPARs. Mol Neurobiol 54:2518–2538. https://doi.org/10.1007/s12035-016-9833-2CrossRefPubMed

Jin Z, Ke J, Guo P, Wang Y, Wu H (2019) Quercetin improves blood-brain barrier dysfunction in rats with cerebral ischemia reperfusion via wnt signaling pathway. Am J Transl Res 11:4683PubMedPubMedCentral

Jiwaji Z, Tiwari SS, Avilés-Reyes RX, Hooley M, Hampton D, Torvell M, Johnson DA, McQueen J, Baxter P, Sabari-Sankar K, Qiu J (2022) Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to tau and Aß pathology. Nat Commun 13:1–23. https://doi.org/10.1038/s41467-021-27702-wCrossRef

Jope RS, Cheng Y, Lowell JA, Worthen RJ, Sitbon YH, Beurel E (2017) Stressed and inflamed, can GSK3 be blamed? Trends Biochem Sci 42:180–192. https://doi.org/10.1016/j.tibs.2016.10.009CrossRefPubMed

Karimaian A, Majidinia M, Baghi HB, Yousefi B (2017) The crosstalk between Wnt/β-catenin signaling pathway with DNA damage response and oxidative stress: implications in cancer therapy. DNA Repair 51. https://doi.org/10.1016/j.dnarep.2017.01.003.:14 – 9

Kasahara E, Inoue M (2015) Cross-talk between HPA-axis-increased glucocorticoids and mitochondrial stress determines immune responses and clinical manifestations of patients with sepsis. Redox Rep 20:1–0. https://doi.org/10.1179/1351000214Y.0000000107CrossRefPubMed

Kim Y, Cho AY, Kim HC, Ryu D, Jo SA, Jung YS (2022) Effects of natural polyphenols on oxidative stress-mediated blood-brain barrier dysfunction. Antioxidants 11:197. https://doi.org/10.3390/antiox11020197CrossRefPubMedPubMedCentral

Konishi K, Cherkerzian S, Aroner S, Jacobs EG, Rentz DM, Remington A, Aizley H, Hornig M, Klibanski A, Goldstein JM (2020) Impact of BDNF and sex on maintaining intact memory function in early midlife. Neurobiol Aging 88:137–149. https://doi.org/10.1016/j.neurobiolaging.2019.12.014CrossRefPubMed

Koshkina A, Volkova O, Fedotova J (2019) Vitamin D3 modulates NF-kB/p65, 17β-Estradiol, and vitamin D receptors expression at Estrogen Deficiency. https://doi.org/10.5772/intechopen.89357. InVitamin D Deficiency. IntechOpen

Lee KH, Yoo CG (2013) Simultaneous inactivation of GSK-3β suppresses quercetin-induced apoptosis by inhibiting the JNK pathway. Am J Physiol Lung Cell Mol Physiol 304:L782–L789. https://doi.org/10.1152/ajplung.00348.2012CrossRefPubMed

Lu Y, Sareddy GR, Wang J, Zhang Q, Tang FL, Pratap UP, Tekmal RR, Vadlamudi RK, Brann DW (2020) Neuron-derived estrogen is critical for astrocyte activation and neuroprotection of the ischemic brain. J Neurosci 40:7355–7374. https://doi.org/10.1523/JNEUROSCI.0115-20.2020CrossRefPubMedPubMedCentral

Ma B, Hottiger MO (2016) Crosstalk between Wnt/β-catenin and NF-κB signaling pathway during inflammation. Front Immunol 7:378. https://doi.org/10.3389/fimmu.2016.00378CrossRefPubMedPubMedCentral

Maggioli E, McArthur S, Mauro C, Kieswich J, Kusters DH, Reutelingsperger CP, Yaqoob M, Solito E (2016) Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking. Brain Behav Immun 51:212–222. https://doi.org/10.1016/j.bbi.2015.08.020CrossRefPubMed

Maher P (2019) The potential of flavonoids for the treatment of neurodegenerative diseases. Int J Mol Sci 20:3056. https://doi.org/10.3390/ijms20123056CrossRefPubMedPubMedCentral

Mazumder AG, Patial V, Singh D (2019) Mycophenolate mofetil contributes to downregulation of the hippocampal interleukin type 2 and 1β mediated PI3K/AKT/mTOR pathway hyperactivation and attenuates neurobehavioral comorbidities in a rat model of temporal lobe epilepsy. Brain Behav Immun 75:84–93. https://doi.org/10.1016/j.bbi.2018.09.020CrossRefPubMed

Mehta J, Kling JM, Manson JE (2021) Risks, benefits, and treatment modalities of menopausal hormone therapy: current concepts. Front Endocrinol 12:564781. https://doi.org/10.3389/fendo.2021.564781CrossRef

Newhouse PA, Dumas J, Hancur-Bucci C, Naylor M, Sites CK, Benkelfat C, Young SN (2008) Estrogen administration negatively alters mood following monoaminergic depletion and psychosocial stress in postmenopausal women. Neuropsychopharmacology 33:1514–1527. https://doi.org/10.1038/sj.npp.1301530CrossRefPubMed

Pan MH, Lai CS, Ho CT (2010) Anti-inflammatory activity of natural dietary flavonoids. Food Funct 1:15–31. https://doi.org/10.1039/C0FO00103ACrossRefPubMed

Pinto-Almazan R, Calzada‐Mendoza CC, Campos‐Lara MG, Guerra‐Araiza C (2012) Effect of chronic administration of estradiol, progesterone, and tibolone on the expression and phosphorylation of glycogen synthase kinase‐3β and the microtubule‐associated protein tau in the hippocampus and cerebellum of female rat. J Neurosci Res 90:878–886. https://doi.org/10.1002/jnr.22808CrossRefPubMed

Rana AK, Singh D (2018) Targeting glycogen synthase kinase-3 for oxidative stress and neuroinflammation: Opportunities, challenges and future directions for cerebral stroke management. Neuropharmacology 139:124–136. https://doi.org/10.1016/j.neuropharm.2018.07.006CrossRefPubMed

Rana AK, Sharma S, Singh D (2020) Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat. Compr Psychoneuroendocrinology 4:100019. https://doi.org/10.1016/j.cpnec.2020.100019CrossRef

Rana AK, Rahmatkar SN, Kumar A, Singh D (2021) Glycogen synthase kinase-3: a putative target to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Cytokine Growth Factor Rev 58:92–101CrossRefPubMed

Rana AK, Sharma S, Patial V, Singh D (2022a) Lithium therapy subdues neuroinflammation to maintain pyramidal cells arborization and rescues neurobehavioural impairments in ovariectomized rats. Mol Neurobiol 11:1–8. https://doi.org/10.1007/s12035-021-02719-wCrossRef

Rana AK, Sharma S, Saini SK, Singh D (2022b) Rutin protects hemorrhagic stroke development via supressing oxidative stress and inflammatory events in a zebrafish model. Eur J Pharmacol 925:174973. https://doi.org/10.1016/j.ejphar.2022.174973CrossRefPubMed

Ren R, Shi C, Cao J, Sun Y, Zhao X, Guo Y, Wang C, Lei H, Jiang H, Ablat N, Xu J (2016) Neuroprotective effects of a standardized flavonoid extract of safflower against neurotoxin-induced cellular and animal models of Parkinson’s disease. Sci Rep 6:1–3. https://doi.org/10.3390/molecules21091107CrossRef

Rizor A, Pajarillo E, Johnson J, Aschner M, Lee E (2019) Astrocytic oxidative/nitrosative stress contributes to Parkinson’s disease pathogenesis: the dual role of reactive astrocytes. Antioxidants 8:265. https://doi.org/10.3390/antiox8080265CrossRefPubMedPubMedCentral

Selvakumar K, Prabha RL, Saranya K, Bavithra S, Krishnamoorthy G, Arunakaran J (2013) Polychlorinated biphenyls impair blood–brain barrier integrity via disruption of tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar rats: neuropotential role of quercetin. Hum Exp Toxicol 32:706–720. https://doi.org/10.1177/0960327112464798CrossRefPubMed

Sharma S, Sharma M, Rana AK, Joshi R, Swarnkar MK, Acharya V, Singh D (2021) Deciphering key regulators involved in epilepsy-induced cardiac damage through whole transcriptome and proteome analysis in a rat model. Epilepsia 62:504–516. https://doi.org/10.1111/epi.16794CrossRefPubMed

Singh A, Kukreti R, Saso L, Kukreti S (2019) Oxidative stress: a key modulator in neurodegenerative diseases. Molecules 24:1583. https://doi.org/10.3390/molecules24081583CrossRefPubMedPubMedCentral

Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H (2018) Antioxidant and oxidative stress: a mutual interplay in age-related diseases. Front Pharmacol 9:1162. https://doi.org/10.3389/fphar.2018.01162CrossRefPubMedPubMedCentral

Torrens-Mas M, Pons DG, Sastre-Serra J, Oliver J, Roca P (2020) Sexual hormones regulate the redox status and mitochondrial function in the brain. Pathological implications. Redox Biol 31:101505. https://doi.org/10.1016/j.redox.2020.101505CrossRefPubMedPubMedCentral

Tran KA, Zhang X, Predescu D, Huang X, Machado RF, Göthert JR, Malik AB, Valyi-Nagy T, Zhao YY (2016) Endothelial β-catenin signaling is required for maintaining adult blood–brain barrier integrity and central nervous system homeostasis. Circulation 133:177–186. https://doi.org/10.1161/CIRCULATIONAHA.115.015982CrossRefPubMed

Xiao H, Deng M, Yang B, Tang J, Hu Z (2017) Role of glycogen synthase kinase 3 in ischemia-induced blood–brain barrier disruption in aged female rats. J Neurochem 142:194–203. https://doi.org/10.1111/jnc.14051CrossRefPubMed

Xu SL, Bi CW, Choi RC, Zhu KY, Miernisha A, Dong TT, Tsim KW (2013) Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured rat astrocytes: a signaling response mediated by estrogen receptor. J Evid Based Complementary Altern Med 2013. https://doi.org/10.1155/2013/127075

Zhang ZL, Zhou ML, Tang Y, Li FL, Tang YX, Shao JR, Xue WT, Wu YM (2012) Bioactive compounds in functional buckwheat food. Food Res Int 49:389–395. https://doi.org/10.1016/j.foodres.2012.07.035CrossRef

Zhou M, Ren H, Han J, Wang W, Zheng Q, Wang D (2015) Protective effects of kaempferol against myocardial ischemia/reperfusion injury in isolated rat heart via antioxidant activity and inhibition of glycogen synthase kinase-3. Oxid Med Cell Longev 2015. https://doi.org/10.1155/2015/481405

Zhu F (2016) Chemical composition and health effects of Tartary buckwheat. Food Chem 203:231–245. https://doi.org/10.1016/j.foodchem.2016.02.050CrossRefPubMed

Zou L, Wu D, Ren G, Hu Y, Peng L, Zhao J, Garcia-Perez P, Carpena M, Prieto MA, Cao H, Cheng KW (2021) Bioactive compounds, health benefits, and industrial applications of Tartary buckwheat (Fagopyrum tataricum). Crit Rev Food Sci Nutr 19:1–17. https://doi.org/10.1080/10408398.2021.1952161CrossRef

Titel: Buckwheat tartary regulates the Gsk-3β/β-catenin pathway to prevent neurobehavioral impairments in a rat model of surgical menopause
verfasst von: Anil Kumar Rana
Supriya Sharma
Rajneesh Kumar
Damanpreet Singh
Publikationsdatum: 03.05.2023
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 6/2023
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-023-01213-7

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