Skip to main content

Advertisement

SpringerLink
Log in

Neuroprotective Effects of Probiotic Lactobacillus reuteri GMNL-263 in the Hippocampus of Streptozotocin-Induced Diabetic Rats

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

Diabetes-related brain complications have been reported in clinical patients and experimental models. The objective of the present study was to investigate the neuroprotective mechanisms of Lactobacillus reuteri GMNL-263 in streptozotocin (STZ)-induced diabetic rats. In this study, three different groups, namely control group, STZ-induced (55 mg/kg streptozotocin intraperitoneally) diabetic rats (DM), and DM rats treated with Lactobacillus reuteri GMNL-263 (1 × 109 CFU/rat/day), were utilized to study the protective effect of GMNL-263 in the hippocampus of STZ-induced diabetic rats. The results demonstrated that GMNL-263 attenuated diabetes-induced hippocampal damage by enhancing the cell survival pathways and repressing both inflammatory and apoptotic pathways. Histopathological analysis revealed that GMNL-263 prevented structural changes in the hippocampus in the DM group and decreased the level of inflammation and apoptosis in the hippocampus of DM rats. The IGF1R cell survival signaling pathway also improved after GMNL-263 treatment. These results indicate that probiotic GMNL-263 exerts beneficial effects in the brain of diabetic rats and has potential ability for clinical application.

Graphical abstract

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Availability of Data and Material

The raw data used and/or analyzed during the current study are available from the corresponding author on reasonable request. The authors confirm that the data supporting the findings of this study are available within the article.

Abbreviations

AMPKα:

AMP-activated protein kinase α

COX-2:

Cyclooxygenase-2

DM:

Diabetes mellitus

GLUT:

Glucose transporter protein

HE:

Hematoxylin and eosin

iNOS:

Inducible nitric oxide synthase

IGF1:

Insulin-like growth factor 1

IGF1R:

Insulin-like growth factor 1 receptor

STZ:

Streptozotocin

TNF-α:

Tumor necrosis factor alpha

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

References

  1. Tabish SA (2007) Is diabetes becoming the biggest epidemic of the twenty-first century? Int J Health Sci (Qassim). 1(2):V–VIII

    PubMed  PubMed Central  Google Scholar 

  2. Shad FS, Haghighi MJ (2018) Study of the effect of the essential oil (extract) of rhubarb stem (shoot) on glycosylated hemoglobin and fasting blood glucose levels in patients with type II diabetes. Biomedicine (Taipei). https://doi.org/10.1051/bmdcn/2018080424

    Article  Google Scholar 

  3. Sima AA, Zhang W, Kreipke CW, Rafols JA, Hoffman WH (2009) Inflammation in diabetic encephalopathy is prevented by C-peptide. Rev Diabet Stud 6(1):37. https://doi.org/10.1900/RDS.2009.6.37

    Article  PubMed  PubMed Central  Google Scholar 

  4. Thakur AK, Tyagi S, Shekhar N (2019) Comorbid brain disorders associated with diabetes: therapeutic potentials of prebiotics, probiotics and herbal drugs. Transl Med Commun 4(1):1–13. https://doi.org/10.1186/s41231-019-0043-6

    Article  Google Scholar 

  5. Li ZG, Zhang W, Grunberger G, Sima AA (2002) Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 946(2):221–231. https://doi.org/10.1016/S0006-8993(02)02887-1

    Article  CAS  PubMed  Google Scholar 

  6. Toth C, Schmidt AM, Tuor UI, Francis G, Foniok T, Brussee V, Kaur J, Yan SF, Martinez JA, Barber PA, Buchan A, Zochodne DW (2006) Diabetes, leukoencephalopathy and rage. Neurobiol Dis 23(2):445–461. https://doi.org/10.1016/j.nbd.2006.03.015

    Article  CAS  PubMed  Google Scholar 

  7. Sima AA, Zhang W, Muzik O, Kreipke CW, Rafols JA, Hoffman WH (2009) Sequential abnormalities in type 1 diabetic encephalopathy and the effects of C-peptide. Rev Diabet Stud 6(3):211–222. https://doi.org/10.1900/RDS.2009.6.211

    Article  PubMed  PubMed Central  Google Scholar 

  8. Munhoz CD, Garcia-Bueno B, Madrigal JL, Lepsch LB, Scavone C, Leza JC (2008) Stress-induced neuroinflammation: mechanisms and new pharmacological targets. Braz J Med Biol Res 41(12):1037–1046. https://doi.org/10.1590/S0100-879X2008001200001

    Article  CAS  PubMed  Google Scholar 

  9. Culmsee C, Landshamer S (2006) Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res 3(4):269–283. https://doi.org/10.2174/156720506778249461

    Article  CAS  PubMed  Google Scholar 

  10. Huang CY, Kuo WW, Wang HF, Lin CJ, Lin YM, Chen JL, Kuo CH, Chen PK, Lin JY (2014) GABA tea ameliorates cerebral cortex apoptosis and autophagy in streptozotocin-induced rats. J Funct Foods 6:534–544. https://doi.org/10.1016/j.jff.2013.11.020

    Article  Google Scholar 

  11. Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA, McGoldrick DJ, Bandi SR, Calabrese CR, Vande Walle L, Lamkanfi M, Kanneganti TD (2014) Dietary modulation of the microbiome affects autoinflammatory disease. Nature 516(7530):246–249. https://doi.org/10.1038/nature13788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kaur IP, Chopra K, Saini A (2002) Probiotics: potential pharmaceutical applications. Eur J Pharm Sci 15(1):1–9. https://doi.org/10.1016/S0928-0987(01)00209-3

    Article  CAS  PubMed  Google Scholar 

  13. Brady LJ, Gallaher DD, Busta FF (2000) The role of probiotic cultures in the prevention of colon cancer. J Nutr 130(2S Suppl):410S-414S. https://doi.org/10.1093/jn/130.2.410S

    Article  CAS  PubMed  Google Scholar 

  14. Liang TW, Wu YY, Huang TY, Wang CY, Yen YH, Liu CP, Chen YC, Wang SL (2010) Conversion of squid pen by a novel strain Lactobacillus paracasei subsp. paracasei TKU010, and its application in antimicrobial and antioxidants activity. J Gen Appl Microbiol 56(6):481–489. https://doi.org/10.2323/jgam.56.481

    Article  CAS  PubMed  Google Scholar 

  15. Lu YC, Yin LT, Chang WT, Huang JS (2010) Effect of Lactobacillus reuteri GMNL-263 treatment on renal fibrosis in diabetic rats. J Biosci Bioeng 110(6):709–715. https://doi.org/10.1016/j.jbiosc.2010.07.006

    Article  CAS  PubMed  Google Scholar 

  16. Koay KP, Tsai BCK, Kuo CH, Kuo WW, Luk HN, Day CH, Chen RJ, Chen MYC, Padma VV, Huang CY (2021) Hyperglycemia-induced cardiac damage is alleviated by heat-inactivated lactobacillus reuteri GMNL-263 via activation of the IGF1R survival pathway. Probiotics Antimicrob Proteins 13(4):1044–1053. https://doi.org/10.1007/s12602-021-09745-z

    Article  CAS  PubMed  Google Scholar 

  17. Chiang CJ, Tsai BCK, Lu TL, Chao YP, Day CH, Ho TJ, Wang PN, Lin SC, Padma VV, Kuo WW (2021) Diabetes-induced cardiomyopathy is ameliorated by heat-killed Lactobacillus reuteri GMNL-263 in diabetic rats via the repression of the Toll-like receptor 4 pathway. Eur J Nutr 60(6):3211–3223. https://doi.org/10.1007/s00394-020-02474-z

    Article  CAS  PubMed  Google Scholar 

  18. Mohammadi G, Dargahi L, Naserpour T, Mirzanejad Y, Alizadeh SA, Peymani A, Nassiri-Asl M (2019) Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats. Int Microbiol 22(3):317–323. https://doi.org/10.1007/s10123-018-00051-3

    Article  CAS  PubMed  Google Scholar 

  19. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108(38):16050–16055. https://doi.org/10.1073/pnas.1102999108

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, Malinowski P, Jackson W, Blennerhassett P, Neufeld KA, Lu J, Khan WI, Corthesy-Theulaz I, Cherbut C, Bergonzelli GE, Collins SM (2010) Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139(6):2102-2112.e1. https://doi.org/10.1073/pnas.1102999108

    Article  PubMed  Google Scholar 

  21. Davari S, Talaei SA, Alaei H, Salami M (2013) Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience 240:287–296. https://doi.org/10.1016/j.neuroscience.2013.02.055

    Article  CAS  PubMed  Google Scholar 

  22. Ting WJ, Kuo WW, Kuo CH, Yeh YL, Shen CY, Chen YH, Ho TJ, Viswanadha VP, Chen YH, Huang CY (2015) Supplementary heat-killed Lactobacillus reuteri GMNL-263 ameliorates hyperlipidaemic and cardiac apoptosis in high-fat diet-fed hamsters to maintain cardiovascular function. Br J Nutr 114(5):706–712. https://doi.org/10.1017/S0007114515002469

    Article  CAS  PubMed  Google Scholar 

  23. Albus U (2012) Guide for the care and use of laboratory animals, 8th edn. London, England, SAGE Publications Sage UK

    Google Scholar 

  24. Chiu WC, Yang HH, Chiang SC, Chou YX, Yang HT (2014) Auricularia polytricha aqueous extract supplementation decreases hepatic lipid accumulation and improves antioxidative status in animal model of nonalcoholic fatty liver. Biomedicine (Taipei) 4(2):1–10. https://doi.org/10.7603/s40681-014-0012-3

    Article  Google Scholar 

  25. Yeh YL, Lu MC, Tsai BCK, Tzang BS, Cheng SM, Zhang X, Yang LY, Mahalakshmi B, Kuo WW, Xiang P, Huang CY (2021) Heat-killed Lactobacillus reuteri GMNL-263 inhibits systemic lupus erythematosus–induced cardiomyopathy in NZB/W F1 mice. Probiotics Antimicro Prot 13(1):51–59. https://doi.org/10.1007/s12602-020-09668-1

    Article  CAS  Google Scholar 

  26. Achudhan D, Chang SL-Y, Liu S-C, Lin Y-Y, Huang W-C, Wu Y-C, Huang C-C, Tsai C-H, Ko C-Y, Kuo Y-H (2022) Antcin K inhibits VCAM-1-dependent monocyte adhesion in human rheumatoid arthritis synovial fibroblasts. Food Nutr Res 66. https://doi.org/10.29219/fnr.v66.8645

  27. Liu S-P, Shibu MA, Tsai F-J, Hsu Y-M, Tsai C-H, Chung J-G, Yang J-S, Tang C-H, Wang S, Li Q, Huang C-Y (2020) Tetramethylpyrazine reverses high-glucose induced hypoxic effects by negatively regulating HIF-1α induced BNIP3 expression to ameliorate H9c2 cardiomyoblast apoptosis. Nutr Metab (Lond) 17(1):1–9. https://doi.org/10.1186/s12986-020-0432-x

    Article  CAS  PubMed  Google Scholar 

  28. Lin WY, Tsai BCK, Day CH, Chiu PL, Chen RJ, Chen MYC, Padma VV, Luk HN, Lee HC, Huang CY (2021) Arecoline induces heart injure via Fas/Fas ligand apoptotic pathway in heart of Sprague-Dawley rat. Environ Toxicol 36(8):1567–1575. https://doi.org/10.1002/tox.23153

    Article  CAS  PubMed  Google Scholar 

  29. Chang WS, Tsai CW, Yang JS, Hsu YM, Shih LC, Chiu HY, Bau DT, Tsai FJ (2021) Resveratrol inhibited the metastatic behaviors of cisplatin-resistant human oral cancer cells via phosphorylation of ERK/p-38 and suppression of MMP-2/9. J Food Biochem 45(6):e13666. https://doi.org/10.1111/jfbc.13666

    Article  CAS  PubMed  Google Scholar 

  30. Ho TJ, Tsai BC, Kuo CH, Luk HN, Day CH, Hsieh DJ, Chen RJ, Kuo WW, Kumar VB, Yao CH, Huang CY (2022) Arecoline induces cardiotoxicity by upregulating and activating cardiac hypertrophy-related pathways in Sprague-Dawley rats. Chem Biol Interact 354:109810. https://doi.org/10.1016/j.cbi.2022.109810

    Article  CAS  PubMed  Google Scholar 

  31. Lin CH, Lin CC, Shibu MA, Liu CS, Kuo CH, Tsai FJ, Tsai CH, Hsieh CH, Chen YH, Huang CY (2014) Oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced diabetes mellitus. Br J Nutr 111(4):598–605. https://doi.org/10.1017/S0007114513002791

    Article  CAS  PubMed  Google Scholar 

  32. Luo J, Wang T, Liang S, Hu X, Li W, Jin F (2014) Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Sci China Life Sci 57(3):327–335. https://doi.org/10.1017/S0007114513002791

    Article  CAS  PubMed  Google Scholar 

  33. Cerdó T, Ruíz A, Suárez A, Campoy C (2017) Probiotic, prebiotic, and brain development. Nutrients 9(11):1247. https://doi.org/10.3390/nu9111247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hsieh FC, Lee CL, Chai CY, Chen WT, Lu YC, Wu CS (2013) Oral administration of Lactobacillus reuteri GMNL-263 improves insulin resistance and ameliorates hepatic steatosis in high fructose-fed rats. Nutr Metab (Lond) 10(1):1–14. https://doi.org/10.1186/1743-7075-10-35

    Article  CAS  Google Scholar 

  35. Zhang D, Jiang S, Meng H (2015) Role of the insulin-like growth factor type 1 receptor in the pathogenesis of diabetic encephalopathy. Int J Endocrinol 2015:626019. https://doi.org/10.1155/2015/626019

    Article  PubMed  PubMed Central  Google Scholar 

  36. Russo VC, Kobayashi K, Najdovska S, Baker NL, Werther GA (2004) Neuronal protection from glucose deprivation via modulation of glucose transport and inhibition of apoptosis: a role for the insulin-like growth factor system. Brain Res 1009(1–2):40–53. https://doi.org/10.1016/j.brainres.2004.02.042

    Article  CAS  PubMed  Google Scholar 

  37. Genis L, Dávila D, Fernandez S, Pozo-Rodrigálvarez A, Martínez-Murillo R, Torres-Aleman I (2014) Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury. F1000Research 3:28. https://doi.org/10.12688/f1000research.3-28.v2

  38. Chen W, He B, Tong W, Zeng J, Zheng P (2019) Astrocytic insulin-like growth factor-1 protects neurons against excitotoxicity. Front Cell Neurosci 13:298. https://doi.org/10.3389/fncel.2019.00298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Aksu I, Ates M, Baykara B, Kiray M, Sisman AR, Buyuk E, Baykara B, Cetinkaya C, Gumus H, Uysal N (2012) Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in streptozotocin induced diabetes. Neurosci Lett 531(2):176–181. https://doi.org/10.1016/j.neulet.2012.10.045

    Article  CAS  PubMed  Google Scholar 

  40. Lay S, Kuo WW, Shibu MA, Ho TJ, Cheng SM, Day CH, Ban B, Wang S, Li Q, Huang CY (2021) Exercise training restores IGFIR survival signaling in d-galactose induced-aging rats to suppress cardiac apoptosis. J Adv Res 28:35–41. https://doi.org/10.1016/j.jare.2020.06.015

    Article  CAS  PubMed  Google Scholar 

  41. Lin JY, Ho TJ, Tsai BCK, Chiang CY, Kao HC, Kuo WW, Chen RJ, Viswanadha VP, Huang CW, Huang CY (2021) Exercise renovates H2S and Nrf2-related antioxidant pathways to suppress apoptosis in the natural ageing process of male rat cortex. Biogerontology 22(5):495–506. https://doi.org/10.1007/s10522-021-09929-8

    Article  CAS  PubMed  Google Scholar 

  42. Tsai BCK, Hsieh DJY, Lin WT, Tamilselvi S, Day CH, Ho TJ, Chang RL, Viswanadha VP, Kuo CH, Huang CY (2020) Functional potato bioactive peptide intensifies Nrf2-dependent antioxidant defense against renal damage in hypertensive rats. Food Res Int 129:108862. https://doi.org/10.1016/j.foodres.2019.108862

    Article  CAS  PubMed  Google Scholar 

  43. Szablewski L (2021) Brain glucose transporters: role in pathogenesis and potential targets for the treatment of Alzheimer’s disease. Int J Mol Sci 22(15):8142. https://doi.org/10.3390/ijms22158142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shah K, Desilva S, Abbruscato T (2012) The role of glucose transporters in brain disease: diabetes and Alzheimer’s disease. Int J Mol Sci 13(10):12629–12655. https://doi.org/10.3390/ijms131012629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Teppala S, Shankar A (2010) Association between serum IGF-1 and diabetes among U.S. adults. Diabetes Care 33(10):2257–2259. https://doi.org/10.2337/dc10-0770

    Article  PubMed  PubMed Central  Google Scholar 

  46. Yu J, Li J, Zhang S, Xu X, Zheng M, Jiang G, Li F (2012) IGF-1 induces hypoxia-inducible factor 1α-mediated GLUT3 expression through PI3K/Akt/mTOR dependent pathways in PC12 cells. Brain Res 1430:18–24. https://doi.org/10.1016/j.brainres.2011.10.046

    Article  CAS  PubMed  Google Scholar 

  47. Delafontaine P, Song YH, Li Y (2004) Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler Thromb Vasc Biol 24(3):435–444. https://doi.org/10.1161/01.ATV.0000105902.89459.09

    Article  CAS  PubMed  Google Scholar 

  48. Aghanoori MR, Smith DR, Shariati-Ievari S, Ajisebutu A, Nguyen A, Desmond F, Jesus CH, Zhou X, Calcutt NA, Aliani M (2019) Insulin-like growth factor-1 activates AMPK to augment mitochondrial function and correct neuronal metabolism in sensory neurons in type 1 diabetes. Mol Metab 20:149–165. https://doi.org/10.1016/j.molmet.2018.11.008

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the China Medical University Hospital, China Medical University, Asia University (DMR-106–176 and CMU107-ASIA-07), and by the Hualien Tzu Chi Hospital (Buddhist Tzu Chi Medical Foundation) (IMAR-110–01-13).

Author information

Author notes

  1. Wei-Wen Kuo and Chih-Yang Huang contributed equally to this paper.

Authors and Affiliations

  1. Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan

    Jing-Ying Lin

  2. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Bruce Chi-Kang Tsai, Chien-Yi Chiang & Chih-Yang Huang

  3. Department of Public Health, Tzu Chi University, Hualien, Taiwan

    Hui-Chuan Kao

  4. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan

    Yun-An Chen & Wei-Wen Kuo

  5. Department of Psychiatry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    William Shao-Tsu Chen

  6. School of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    William Shao-Tsu Chen

  7. Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  8. Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  9. School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  10. Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan

    Chun-Hsu Yao

  11. School of Chinese Medicine, China Medical University, Taichung, Taiwan

    Chun-Hsu Yao

  12. Biomaterials Translational Research Center, China Medical University Hospital, Taichung, Taiwan

    Chun-Hsu Yao

  13. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan

    Chun-Hsu Yao

  14. Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  15. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

  16. Center of General Education, Tzu Chi University of Science and Technology, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Chih-Yang Huang

  17. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

  18. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

Authors
  1. Jing-Ying Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruce Chi-Kang Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hui-Chuan Kao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chien-Yi Chiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun-An Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. William Shao-Tsu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tsung-Jung Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chun-Hsu Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei-Wen Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chih-Yang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Jing-Ying Lin and Chih-Yang Huang conceptualized and designed the study. Bruce Chi-Kang Tsai, Chien-Yi Chiang, and Yun-An Chen collected and assembled the data. Jing-Ying Lin, Chun-Hsu Yao, and Hui-Chuan Kao provided materials for the study. Yun-An Chen, William Shao-Tsu Chen and Tsung-Jung Ho analyzed and interpreted the data. Bruce Chi-Kang Tsai and Chien-Yi Chiang wrote the draft of the manuscript. Tsung-Jung Ho, Wei-Wen Kuo and Chih-Yang Huang reviewed and gave the final approval of the manuscript. Jing-Ying Lin, Tsung-Jung Ho, and Wei-Wen Kuo provided the administrative support. Chun-Hsu Yao, Wei-Wen Kuo and Chih-Yang Huang provided financial support.

Corresponding author

Correspondence to Chih-Yang Huang.

Ethics declarations

Ethics Approval and Consent to Participate

All experimental protocols were approved by the Institutional Animal Care and Use Committee of China Medical University, Taichung, Taiwan.

Consent for Publication

The authors agree the publication.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Highlights

• GMNL-263 suppresses diabetes-induced damage in the hippocampus.

• GMNL-263 reduces inflammation and apoptosis in the diabetic hippocampus. 

• GMNL-263 improves IGF1R/AMPK/GLUT3 to prevent damage in diabetic hippocampus. 

• GMNL-263 can potentially be used to prevent diabetic-induced hippocampus injury. 

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1791 kb)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, JY., Tsai, B.CK., Kao, HC. et al. Neuroprotective Effects of Probiotic Lactobacillus reuteri GMNL-263 in the Hippocampus of Streptozotocin-Induced Diabetic Rats. Probiotics & Antimicro. Prot. 15, 1287–1297 (2023). https://doi.org/10.1007/s12602-022-09982-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-022-09982-w

Keywords

Search

Navigation