Skip to main content

Advertisement

Log in

Ginkgo biloba Extract (GbE) Restores Serotonin and Leptin Receptor Levels and Plays an Antioxidative Role in the Hippocampus of Ovariectomized Rats

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Since Ginkgo biloba extract (GbE) was reported to improve the hypothalamic serotonergic system of ovariectomized (OVX) rats, the present study aimed to verify the GbE effects on hippocampal oxidative stress, inflammation, and levels of the serotonin transporter (5-HTT), and both the serotonin (5-HT1A, 5-HT1B) and leptin receptors of OVX rats. Two-month-old female Wistar rats had their ovaries surgically removed (OVX) or not (SHAM). After 60 days, OVX rats were gavaged daily with GbE 500 mg kg−1 (OVX+GbE), while SHAM and OVX groups received saline 0.9% (vehicle) for 14 days. Rats were then euthanized, and hippocampi were collected. Both 5-HT1A and 5-HT1B levels were significantly reduced in OVX rats compared to SHAM rats, while 5-HT1A was higher in OVX+GbE rats in comparison to OVX rats. Similarly, LepR levels were increased in OVX+GbE rats compared to OVX rats, reaching similar levels to SHAM rats. Superoxide dismutase activity increased in OVX rats in relation to SHAM rats, which was restored to SHAM levels by GbE treatment. Additionally, GbE significantly increased the glutathione peroxidase activity in comparison to the SHAM group. No differences were observed either in catalase activity or in the levels of 5-HTT, PKCα, TLR-4, NF-κBp50, ERK, and CREB. In summary, our results show a potential effect of GbE on hippocampal pathways involved in feeding behavior, and thus, they suggest that GbE activity might improve menopausal-related hippocampal disorders, offering an alternative therapeutic tool particularly for women to whom hormone replacement therapy may be contraindicated.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

All data generated or analyzed in the study will be available in the repository, as well as by the corresponding author upon request.

References

  1. Herrera AY, Mather M (2015) Actions and interactions of estradiol and glucocorticoids in cognition and the brain: Implications for aging women. Neurosci Biobehav Rev 55:36–52. https://doi.org/10.1016/j.neubiorev.2015.04.005

    Article  CAS  PubMed Central  Google Scholar 

  2. Xu Y, López M (2018) Central regulation of energy metabolism by estrogens. Mol Metab 15:104–115. https://doi.org/10.1016/j.molmet.2018.05.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McEwen BS (2001) Invited review: estrogens effects on the brain: multiple sites and molecular mechanisms. J Appl Physiol 91:2785–2801. https://doi.org/10.1152/jappl.2001.91.6.2785

    Article  CAS  PubMed  Google Scholar 

  4. Luine VN (2014) Estradiol and cognitive function: past, present and future. Horm Behav 66:602–618. https://doi.org/10.1016/j.yhbeh.2014.08.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Al Abed AS, Sellami A, Brayda-Bruno L et al (2016) Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice. Psychoneuroendocrinology 69:77–89. https://doi.org/10.1016/j.psyneuen.2016.03.014

    Article  CAS  PubMed  Google Scholar 

  6. Brinton RD, Chen S, Montoya M, Hsieh D, Minaya J (2000) The estrogen replacement therapy of the Women’s Health Initiative promotes the cellular mechanisms of memory and neuronal survival in neurons vulnerable to Alzheimer’s disease. Maturitas 34:S35–S52. https://doi.org/10.1016/S0378-5122(00)00107-9

    Article  CAS  PubMed  Google Scholar 

  7. Au A, Feher A, McPhee L, Jessa A, Oh S, Einstein G (2016) Estrogens, inflammation and cognition. Front Neuroendocrinol 40:87–100. https://doi.org/10.1016/j.yfrne.2016.01.002

    Article  CAS  PubMed  Google Scholar 

  8. Inagaki T, Gautreaux C, Luine V (2010) Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm Behav 58:415–426. https://doi.org/10.1161/CIRCULATIONAHA.110.956839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Christensen A, Pike CJ (2015) Menopause, obesity and inflammation: interactive risk factors for Alzheimer’s disease. Front Aging Neurosci 7:1–14. https://doi.org/10.3389/fnagi.2015.00130

    Article  Google Scholar 

  10. Doshi SB (2013) Agarwal A. The role of oxidative stress in menopause 4:140–146. https://doi.org/10.4103/0976-7800.118990

    Article  Google Scholar 

  11. Sorpreso ICE, Soares Júnior JM, da Fonseca AM, Baracat EC (2015) Female aging. Rev Assoc Med Bras 61:553–556. https://doi.org/10.1590/1806-9282.61.06.553

    Article  PubMed  Google Scholar 

  12. Li LH, Wang ZC, Yu J, Zhang YQ (2014) Ovariectomy results in variable changes in nociception, mood and depression in adult female rats. PLoS One 9:1–11. https://doi.org/10.1371/journal.pone.0094312

    Article  CAS  Google Scholar 

  13. Del Río JP, Alliende MI, Molina N et al (2018) Steroid hormones and their action in women’s brains: the importance of hormonal balance. Front Public Heal 6:1–15. https://doi.org/10.3389/fpubh.2018.00141

    Article  Google Scholar 

  14. Dornellas APS, Boldarine VT, Pedroso AP, Carvalho LOT, de Andrade IS, Vulcani-Freitas TM, dos Santos CCC, do Nascimento CMPO et al (2018) High-fat feeding improves anxiety-type behavior induced by ovariectomy in rats. Front Neurosci 12:1–13. https://doi.org/10.3389/fnins.2018.00557

  15. Banin RM, Machado MMF, Telles MM (2017) A bi-directional relation between menopause and obesity: focus on the main causes and associated metabolic diseases. Curr res diabetes Obes J 3:59–61. https://doi.org/10.19080/CRDOJ.2017.3.555609 curre

  16. Kanoski SE, Grill HJ (2017) Review hippocampus contributions to food intake control: mnemonic, neuroanatomical, and endocrine mechanisms. Biol Psychiatry 81:748–756. https://doi.org/10.1016/j.biopsych.2015.09.011

    Article  PubMed  Google Scholar 

  17. Kanoski SE, Hayes MR, Greenwald HS, Fortin SM, Gianessi CA, Gilbert JR, Grill HJ (2011) Hippocampal Leptin signaling reduces food intake and modulates food-related memory processing. Neuropsychopharmacology 36:1859–1870. https://doi.org/10.1038/npp.2011.70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Epperson CN, Amin Z, Rupaurel K et al (2012) NIH public access. Psychoneuroendocrinology 37:372–382. https://doi.org/10.1016/j.psyneuen.2011.07.007.Interactive

    Article  CAS  PubMed  Google Scholar 

  19. Compton J, Van Amelsvoort T, Murphy D (2001) HRT and its effect on normal ageing of the brain and dementia. Br J Clin Pharmacol 52:647–653. https://doi.org/10.1046/j.0306-5251.2001.01492.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Seumeren IV (2000) Weight gain and hormone replacement therapy: are women’s fears justified? Maturitas 34:3–8. https://doi.org/10.1016/S0378-5122(99)00073-0

    Article  Google Scholar 

  21. Hirata BKS, Banin RM, Dornellas APS, de Andrade IS, Zemdegs JCS, Caperuto LC, Oyama LM, Ribeiro EB et al (2015) Ginkgo biloba extract improves insulin signaling and attenuates inflammation in retroperitoneal adipose tissue depot of obese rats. Mediat Inflamm 2015:1–9. https://doi.org/10.1155/2015/419106

  22. Hirata BKS, Pedroso AP, Machado MMF, Neto NIP, Perestrelo BO, de Sá RDCC, Alonso-Vale MIC, Nogueira FN et al (2019) Ginkgo biloba extract modulates the retroperitoneal fat depot proteome and reduces oxidative stress in diet-induced obese rats. Front Pharmacol 10:1–11. https://doi.org/10.3389/fphar.2019.00686

  23. Kennedy D, Wightman E (2011) British pharmacopeia. Adv Nutr 2:32–50. https://doi.org/10.3945/an.110.000117.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Heinonen T, Gaus W (2015) Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract. Toxicology 327:95–115. https://doi.org/10.1016/j.tox.2014.10.013

    Article  CAS  PubMed  Google Scholar 

  25. Banin RM, Hirata BKS, Andrade IS, Zemdegs JCS, Clemente APG, Dornellas APS, Boldarine VT, Estadella D et al (2014) Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats. Brazilian J Med Biol Res 47:780–788. https://doi.org/10.1590/1414-431X20142983

  26. Hirata BKS, Cruz MM, De Sá RDCC et al (2019) Potential anti-obesogenic effects of Ginkgo biloba observed in epididymal white adipose tissue of obese rats. Front Endocrinol (Lausanne) 10:1–11. https://doi.org/10.3389/fendo.2019.00284

    Article  Google Scholar 

  27. Ding S, Dudley E, Plummer S, Tang J, Newton RP, Brenton AG (2006) Quantitative determination of major active components in Ginkgo biloba dietary supplements by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom 20:2753–2760. https://doi.org/10.1002/rcm.2646

    Article  CAS  PubMed  Google Scholar 

  28. Banin RM, de Andrade IS, Cerutti SM, Oyama LM, Telles MM, Ribeiro EB (2017) Ginkgo biloba extract (GbE) stimulates the hypothalamic serotonergic system and attenuates obesity in ovariectomized rats. Front Pharmacol 8:1–11. https://doi.org/10.3389/fphar.2017.00605

    Article  CAS  Google Scholar 

  29. Spijker S (2011) Neuroproteomics: dissection of rodent brain regions. Neuromethods 57:13–27. https://doi.org/10.1007/978-1-61779-111-6

    Article  CAS  Google Scholar 

  30. Aebi H (1984) [13] Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    Article  CAS  PubMed  Google Scholar 

  31. Lovejoy JC, Champagne CM, De Jonge L et al (2008) Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes 32:949–958. https://doi.org/10.1038/ijo.2008.25

    Article  CAS  Google Scholar 

  32. Al-Safi ZA, Polotsky AJ (2015) Obesity and menopause. Best Pract Res Clin Obstet Gynaecol 29:548–553. https://doi.org/10.1016/j.bpobgyn.2014.12.002

    Article  PubMed  Google Scholar 

  33. Boldarine VT, Pedroso AP, Neto NIP, Dornellas APS, Nascimento CMO, Oyama LM, Ribeiro EB (2019) High-fat diet intake induces depressive-like behavior in ovariectomized rats. Sci Rep 9:1–9. https://doi.org/10.1038/s41598-019-47152-1

    Article  CAS  Google Scholar 

  34. Hirata BKS, Cruz MM, De Sá RDCC et al (2019) Potential anti-obesogenic effects of Ginkgo biloba observed in epididymal white adipose tissue of obese rats. Front Endocrinol (Lausanne) 10:10. https://doi.org/10.3389/fendo.2019.00284

    Article  Google Scholar 

  35. Oliveira DR, Sanada PF, Filho ACS, Conceição GMS, Cerutti JM, Cerutti SM (2013) Long-term treatment with standardized extract of Ginkgo biloba L. enhances the conditioned suppression of licking in rats by the modulation of neuronal and glial cell function in the dorsal hippocampus and central amygdala. Neuroscience 235:70–86. https://doi.org/10.1016/j.neuroscience.2013.01.009

    Article  CAS  PubMed  Google Scholar 

  36. Ribeiro ML, Moreira LM, Arçari DP, dos Santos LF, Marques AC, Pedrazzoli J Jr, Cerutti SM (2016) Protective effects of chronic treatment with a standardized extract of Ginkgo biloba L. in the prefrontal cortex and dorsal hippocampus of middle-aged rats. Behav Brain Res 313:144–150. https://doi.org/10.1016/j.bbr.2016.06.029

    Article  CAS  PubMed  Google Scholar 

  37. Gaiardo RB, Abreu TF, Tashima AK, Telles MM, Cerutti SM (2019) Target proteins in the dorsal hippocampal formation sustain the memory-enhancing and neuroprotective effects of Ginkgo biloba. Front Pharmacol 9:1–14. https://doi.org/10.3389/fphar.2018.01533

    Article  CAS  Google Scholar 

  38. Zamberlam CR, Tilger MAS, Moraes L, Cerutti JM, Cerutti SM (2019) Ginkgo biloba treatments reverse the impairment of conditioned suppression acquisition induced by GluN2B-NMDA and 5-HT1A receptor blockade: modulatory effects of the circuitry of the dorsal hippocampal formation. Physiol Behav 209:1–20. https://doi.org/10.1016/j.physbeh.2019.04.023

    Article  CAS  Google Scholar 

  39. Voigt JP, Fink H (2015) Serotonin controlling feeding and satiety. Behav Brain Res 277:14–31. https://doi.org/10.1016/j.bbr.2014.08.065

    Article  CAS  PubMed  Google Scholar 

  40. Butt I, Hong A, Di J et al (2014) The effects of serotonin1A receptor on female mice body weight and food intake are associated with the differential expression of hypothalamic neuropeptides and the GABAA receptor. Neuropeptides 48:313–318. https://doi.org/10.1016/j.npep.2014.07.003

    Article  CAS  PubMed  Google Scholar 

  41. Van Doorn C, Macht VA, Grillo CA, Reagan LP (2017) Leptin resistance and hippocampal behavioral deficits. Physiol Behav 176:207–213. https://doi.org/10.1016/j.physbeh.2017.03.002

    Article  CAS  PubMed  Google Scholar 

  42. Donovan MH, Tecott LH (2013) Serotonin and the regulation of mammalian energy balance. Front Neurosci 7:1–15. https://doi.org/10.3389/fnins.2013.00036

    Article  CAS  Google Scholar 

  43. Telles MM, Guimarães RB, Ribeiro EB (2003) Effect of leptin on the acute feeding-induced hypothalamic serotonergic stimulation in normal rats. Regul Pept 115:11–18. https://doi.org/10.1016/S0167-0115(03)00129-0

    Article  CAS  PubMed  Google Scholar 

  44. Rozin P, Dow S, Moscovitch M, Rajaram S (1998) What causes humans to begin and end a meal? A role for memory for what has been eaten, as evidenced by a study of multiple meal eating in amnesic patients. Psychol Sci 9:392–396. https://doi.org/10.1111/1467-9280.00073

    Article  Google Scholar 

  45. Stevenson RJ, Francis HM (2017) The hippocampus and the regulation of human food intake. Psychol Bull 143:1011–1032. https://doi.org/10.1037/bul0000109

    Article  PubMed  Google Scholar 

  46. Banin RM, Machado MMF, de Andrade IS, et al (2021) Ginkgo biloba extract (GbE) attenuates obesity and anxiety/depressive-like behaviours induced by ovariectomy. Sci Rep 11: 1-14. https://doi.org/10.1038/s41598-020-78528-3

  47. Oliveira DR, Sanada PF, Saragossa FAC, Innocenti LR, Oler G, Cerutti JM, Cerutti SM (2009) Neuromodulatory property of standardized extract Ginkgo biloba L. (EGb 761) on memory: behavioral and molecular evidence. Brain Res 1269:68–89. https://doi.org/10.1016/j.brainres.2008.11.105

    Article  CAS  PubMed  Google Scholar 

  48. Frick KM, Tuscher JJ, Koss WA, Kim J, Taxier LR (2018) Estrogenic regulation of memory consolidation: a look beyond the hippocampus, ovaries, and females. Physiol Behav 187:57–66. https://doi.org/10.1016/j.physbeh.2017.07.028

    Article  CAS  PubMed  Google Scholar 

  49. Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 5:1–15. https://doi.org/10.1017/jns.2016.41

    Article  CAS  Google Scholar 

  50. Feng Z, Sun Q, Chen W, Bai Y, Hu D, Xie X (2019) The neuroprotective mechanisms of ginkgolides and bilobalide in cerebral ischemic injury: a literature review. Mol Med 25:1–8. https://doi.org/10.1186/s10020-019-0125-y

    Article  CAS  Google Scholar 

  51. Mu L, Kou J, Zhu D, Yu B (2007) Comparison of neuroprotective effects of flavonoids, terpenoids, and their combinations from Ginkgo biloba on ischemia-reperfusion - injured mice. Pharm Biol 45:728–733. https://doi.org/10.1080/13880200701575486

    Article  CAS  Google Scholar 

  52. Sagredo A, del Campo L, Martorell A, Navarro R, Martín MC, Blanco-Rivero J, Ferrer M (2013) Ovariectomy increases the participation of hyperpolarizing mechanisms in the relaxation of rat aorta. PLoS One 8:1–11. https://doi.org/10.1371/journal.pone.0073474

  53. Behr GA, Schnorr CE, Simoes-Pires A et al (2012) Increased cerebral oxidative damage and decreased antioxidant defenses in ovariectomized and sham-operated rats supplemented with vitamin a. Cell Biol Toxicol 28:317–330. https://doi.org/10.1007/s10565-012-9226-x

    Article  CAS  PubMed  Google Scholar 

  54. Monthakantirat O, Sukano W, Umehara K, Noguchi H, Chulikhit Y, Matsumoto K (2014) Effect of miroestrol on ovariectomy-induced cognitive impairment and lipid peroxidation in mouse brain. Phytomedicine 21:1249–1255. https://doi.org/10.1016/j.phymed.2014.06.012

    Article  CAS  PubMed  Google Scholar 

  55. Kohen R, Beit-Yannai E, Berry EM, Tirosh O (1999) Overall low molecular weight antioxidant activity of biological fluids and tissues by cyclic voltammetry. Methods Enzymol 300:285–296. https://doi.org/10.1016/S0076-6879(99)00135-4

    Article  CAS  PubMed  Google Scholar 

  56. Griendling KK, Sorescu D, Lassègue B, Ushio-Fukai M (2000) Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20:2175–2183. https://doi.org/10.1161/01.ATV.20.10.2175

    Article  CAS  PubMed  Google Scholar 

  57. Saso L, Firuzi O (2014) Pharmacological applications of antioxidants: lights and shadows. Curr Drug Targets 15:1177–1199. https://doi.org/10.2174/1389450115666141024113925

    Article  CAS  PubMed  Google Scholar 

  58. Huang YH, Zhang QH (2010) Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress. Br J Nutr 104:1297–1303. https://doi.org/10.1017/S0007114510002291

    Article  CAS  PubMed  Google Scholar 

  59. Eckert A (2012) Mitochondrial effects of Ginkgo biloba extract. Int Psychogeriatrics 24:18–20. https://doi.org/10.1017/S1041610212000531

    Article  Google Scholar 

  60. Sadowska-Krępa E, Kłapcińska B, Pokora I, Domaszewski P, Kempa K, Podgórski T (2017) Effects of six-week Ginkgo biloba supplementation on aerobic performance, blood pro/antioxidant balance, and serum brain-derived neurotrophic factor in physically active men. Nutrients 9:1–11. https://doi.org/10.3390/nu9080803

    Article  CAS  Google Scholar 

  61. Rimbach G, Gohil K, Matsugo S, Moini H, Saliou C, Virgili F, Weber SU, Packer L (2001) Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761). BioFactors 15:39–52. https://doi.org/10.1002/biof.5520150104

    Article  CAS  PubMed  Google Scholar 

  62. Shi C, Fang L, Yew DT, Yao Z, Xu J (2010) Ginkgo biloba extract EGb761 protects against mitochondrial dysfunction in platelets and hippocampi in ovariectomized rats. Platelets 21:53–59. https://doi.org/10.3109/09537100903395180

    Article  CAS  PubMed  Google Scholar 

  63. Kaur S, Chhabra R, Nehru B (2013) Ginkgo biloba extract attenuates hippocampal neuronal loss and cognitive dysfunction resulting from trimethyltin in mice. Phytomedicine 20:178–186. https://doi.org/10.1016/j.phymed.2012.10.003

    Article  CAS  PubMed  Google Scholar 

  64. Gaucher C, Boudier A, Bonetti J, Clarot I, Leroy P, Parent M (2018) Glutathione: antioxidant properties dedicated to nanotechnologies. Antioxidants 7:1–21. https://doi.org/10.3390/antiox7050062

    Article  CAS  Google Scholar 

  65. Cai W, Xue C, Sakaguchi M, Konishi M, Shirazian A, Ferris HA, Li ME, Yu R et al (2018) Insulin regulates astrocyte gliotransmission and modulates behavior. J Clin Invest 128:2914–2926. https://doi.org/10.1172/JCI99366

  66. Carter AB, Hunninghake GW (2000) A constitutive active MEK → ERK pathway negatively regulates NF-κB-dependent gene expression by modulating TATA-binding protein phosphorylation. J Biol Chem 275:27858–27864. https://doi.org/10.1074/jbc.M003599200

    Article  CAS  PubMed  Google Scholar 

  67. Klinger MB, Sacks S, Cervero F (2011) A role for extracellular signal-regulated kinases 1 and 2 in the maintenance of persistent mechanical hyperalgesia in ovariectomized mice. Neuroscience 172:483–493. https://doi.org/10.1016/j.neuroscience.2010.10.043

    Article  CAS  PubMed  Google Scholar 

  68. Kim D Il, Choi MS, Pak SC, et al (2012) The effects of Sutaehwan-Gami on menopausal symptoms induced by ovariectomy in rats. BMC Complement Altern Med 12:1–8. https://doi.org/10.1186/1472-6882-12-227

  69. Pereira RTS, Porto CS, Abdalla FMF (2014) Ovariectomy and 17β-estradiol replacement play a role on the expression of endonuclease-G and phosphorylated cyclic AMP response element-binding (CREB) protein in hippocampus. Mol Cell Endocrinol 382:227–233. https://doi.org/10.1016/j.mce.2013.09.037

    Article  CAS  Google Scholar 

  70. Tchantchou F, Xu Y, Wu Y, Christen Y, Luo Y (2007) EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease. FASEB J 21:2400–2408. https://doi.org/10.1096/fj.06-7649com

    Article  CAS  PubMed  Google Scholar 

  71. Zhang W, Song JK, Yan R, Li L, Xiao ZY, Zhou WX, Wang ZZ, Xiao W et al (2018) Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling. Acta Pharmacol Sin 39:1259–1272. https://doi.org/10.1038/aps.2017.149

Download references

Acknowledgments

The authors gratefully acknowledge the support given by Suzete Maria Cerutti, Esther Milani Ático, Nelson Inácio Pinto Neto, Paloma Korehisa Maza, and Carol Anne Dannenhoffer.

Funding

This research was supported by grants from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) [2014/18929-9] and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) [finance code 001].

Author information

Authors and Affiliations

Authors

Contributions

Meira Maria Forcelini Machado—conceptualization, validation, formal analysis, investigation, and data curation

Renata Mancini Banin—conceptualization, methodology, visualization, and supervision

Fernanda Malanconi Thomazconceptualization, methodology, and investigation

Iracema Senna de Andradeconceptualization, methodology, and investigation

Valter Tadeu Boldarineconceptualization, methodology, and investigation

Jéssica de Souza Figueiredoconceptualization, methodology, and investigation

Bruna Kelly Sousa Hirata—conceptualization, methodology, and data curation

Lila Missae Oyama—conceptualization, visualization, and funding acquisition

João Henrique Ghilardi Lago—conceptualization, visualization, methodology, formal analysis, resources, and writing—review and editing

Eliane Beraldi Ribeiro—conceptualization, visualization, and funding acquisition

Mônica Marques Telles—conceptualization, methodology, formal analysis, resources, writing—review and editing, visualization, supervision, project administration, and funding acquisition

Corresponding author

Correspondence to Mônica Marques Telles.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(JPG 171 kb)

ESM 2

(PDF 665 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Machado, M.M.F., Banin, R.M., Thomaz, F.M. et al. Ginkgo biloba Extract (GbE) Restores Serotonin and Leptin Receptor Levels and Plays an Antioxidative Role in the Hippocampus of Ovariectomized Rats. Mol Neurobiol 58, 2692–2703 (2021). https://doi.org/10.1007/s12035-021-02281-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-021-02281-5

Keywords

Navigation