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Goat milk attenuates mimetic aging related memory impairment via suppressing brain oxidative stress, neurodegeneration and modulating neurotrophic factors in d-galactose-induced aging model

  • Afifa Safdar
  • Rahimah Zakaria
  • Che Badariah Ab Aziz
  • Usman Rashid
  • Khairunnuur Fairuz AzmanEmail author
Research Article
  • 17 Downloads

Abstract

One of the most significant hallmarks of aging is cognitive decline. d-galactose administration may impair memory and mimic the effects of natural aging. In this study, the efficiency of goat milk to protect against memory decline was tested. Fifty-two male Sprague–Dawley rats were randomly divided into four groups: (i) control group, (ii) goat milk treated group, (iii) d-galactose treated group, and (iv) goat milk plus d-galactose treated group. Subcutaneous injections of d-galactose at 120 mg/kg and oral administrations of goat milk at 1 g/kg were chosen for the study. Goat milk and d-galactose were administered concomitantly for 6 weeks, while the control group received saline. After 6 weeks, novel object recognition and T-maze tests were performed to evaluate memory of rats. Following behavioral tests, the animals were sacrificed, and right brain homogenates were analyzed for levels of lipid peroxidation, antioxidant enzymes and neurotrophic factors. The left brain hemisphere was used for histological study of prefrontal cortex and hippocampus. There was a significant memory impairment, an increase in oxidative stress and neurodegeneration and a reduction in antioxidant enzymes and neurotrophic factors levels in the brain of d-galactose treated rats compared to controls. Goat milk treatment attenuated memory impairment induced by d-galactose via suppressing oxidative stress and neuronal damage and increasing neurotrophic factors levels, thereby suggesting its potential role as a geroprotective food.

Keywords

Dairy Aging Cognitive Neurodegenerative Oxidative stress Brain-derived neurotrophic factor Mimetic aging d-galactose 

Abbreviations

ROS

Reactive oxygen species

MDA

Malondialdehyde

NGF

Nerve-growth factor

BDNF

Brain-derived neurotrophic factor

SOD

Cu–Zn-superoxide dismutase

GPx

Glutathione peroxidase

CAT

Catalase

DG

Dentate gyrus

CA

Cornus ammonis

mPFC

Medial prefrontal cortex

Notes

Acknowledgements

The authors would like to acknowledge School of Medical Sciences, Universiti Sains Malaysia and short-term research grant of Universiti Sains Malaysia (304/PPSP/6315093) for the financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

References

  1. Ahmed AS, El-Bassiony T, Elmalt LM, Ibrahim HR (2015) Identification of potent antioxidant bioactive peptides from goat milk proteins. Food Res Int 74:80–88PubMedCrossRefPubMedCentralGoogle Scholar
  2. Alférez M, Barrionuevo M, Aliaga IL, Sanz-Sampelayo M, Lisbona F, Robles J, Campos M (2001) Digestive utilization of goat and cow milk fat in malabsorption syndrome. J Dairy Res 68:451–461PubMedCrossRefPubMedCentralGoogle Scholar
  3. Anand KV, Mohamed Jaabir MS, Thomas PA, Geraldine P (2012) Protective role of chrysin against oxidative stress in d-galactose-induced aging in an experimental rat model. Geriatr Gerontol Int 12:741–750PubMedCrossRefPubMedCentralGoogle Scholar
  4. Ano Y, Ozawa M, Kutsukake T, Sugiyama S, Uchida K, Yoshida A, Nakayama H (2015) Preventive effects of a fermented dairy product against Alzheimer’s disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity. PLoS ONE 10:e0118512PubMedPubMedCentralCrossRefGoogle Scholar
  5. Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13:93–110PubMedCrossRefPubMedCentralGoogle Scholar
  6. Azman KF, Zakaria R (2019) d-galactose-induced accelerated aging model: an overview. Biogerontology 20:763–782PubMedCrossRefPubMedCentralGoogle Scholar
  7. Bancroft J, Gamble M (2008) Theory and practice of histology techniques. Churchill Livingstone, London, pp 83–134Google Scholar
  8. Barbosa MQ et al (2018) Effect of diets with goat milk fat supplemented with exercise on anxiety and oxidative stress in the brains of adult rats. Food Funct 9:2891–2901PubMedCrossRefPubMedCentralGoogle Scholar
  9. Bekinschtein P, Cammarota M, Igaz LM, Bevilaqua LR, Izquierdo I, Medina JH (2007) Persistence of long-term memory storage requires a late protein synthesis-and BDNF-dependent phase in the hippocampus. Neuron 53:261–277PubMedCrossRefPubMedCentralGoogle Scholar
  10. Cebe T et al (2014) Oxidation scrutiny in persuaded aging and chronological aging at systemic redox homeostasis level. Exp Gerontol 57:132–140PubMedCrossRefPubMedCentralGoogle Scholar
  11. Chen X, Li Y, Chen W, Nong Z, Huang J, Chen C (2016) Protective effect of hyperbaric oxygen on cognitive impairment induced by d-galactose in mice. Neurochem Res 41:3032–3041PubMedCrossRefPubMedCentralGoogle Scholar
  12. Conner JM et al (2009) NGF is essential for hippocampal plasticity and learning. J Neurosci 29:10883–10889PubMedPubMedCentralCrossRefGoogle Scholar
  13. Cui X et al (2006) Chronic systemic d-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-α-lipoic acid. J Neurosci Res 84:647–654PubMedCrossRefPubMedCentralGoogle Scholar
  14. de Assis POA et al (2016) Intestinal anti-inflammatory activity of goat milk and goat yoghurt in the acetic acid model of rat colitis. Int Dairy J 56:45–54CrossRefGoogle Scholar
  15. Deacon RM, Rawlins JNP (2006) T-maze alternation in the rodent. Nat Protoc 1:7PubMedCrossRefPubMedCentralGoogle Scholar
  16. Díaz-Castro J et al (2012) Influence of cow or goat milk consumption on antioxidant defence and lipid peroxidation during chronic iron repletion. Br J Nutr 108:1–8PubMedCrossRefPubMedCentralGoogle Scholar
  17. Díaz-Castro J et al (2014) Goat milk supplemented with folic acid protects cell biomolecules from oxidative stress-mediated damage after anaemia recovery in comparison with cow milk. Eur J Nutr 53:1165–1175PubMedCrossRefPubMedCentralGoogle Scholar
  18. Erdoğan ME et al (2017) The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer’s disease model. Metab Brain Dis 32:1017–1031PubMedCrossRefPubMedCentralGoogle Scholar
  19. Erraji-Benchekroun L et al (2005) Molecular aging in human prefrontal cortex is selective and continuous throughout adult life. Biol Psychiatry 57:549–558PubMedCrossRefPubMedCentralGoogle Scholar
  20. Fairuz AA, Hashida N, Noor MM (2011) Effect of nicotine and goat milk co-administration on rat testis and sperm parameters. Aust J Basic Appl Sci 5:2738–2741Google Scholar
  21. Gao J et al (2015) Salidroside ameliorates cognitive impairment in a d-galactose-induced rat model of Alzheimer’s disease. Behav Brain Res 293:27–33PubMedCrossRefPubMedCentralGoogle Scholar
  22. Haenlein G (2004) Goat milk in human nutrition. Small Rumin Res 51:155–163CrossRefGoogle Scholar
  23. Haider S et al (2015) A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process. Life Sci 124:110–119PubMedCrossRefPubMedCentralGoogle Scholar
  24. Kanato Y, Kitajima K, Sato C (2008) Direct binding of polysialic acid to a brain-derived neurotrophic factor depends on the degree of polymerization. Glycobiology 18:1044–1053PubMedCrossRefPubMedCentralGoogle Scholar
  25. Kim HY et al (2014) Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer’s disease. Sci Rep 4:7467PubMedPubMedCentralCrossRefGoogle Scholar
  26. Kullisaar T, Songisepp E, Mikelsaar M, Zilmer K, Vihalemm T, Zilmer M (2003) Antioxidative probiotic fermented goats’ milk decreases oxidative stress-mediated atherogenicity in human subjects. Br J Nutr 90:449–456PubMedCrossRefPubMedCentralGoogle Scholar
  27. Lawless F, Murphy J, Harrington D, Devery R, Stanton C (1998) Elevation of conjugated cis-9, trans-11-octadecadienoic acid in bovine milk because of dietary supplementation. J Dairy Sci 81:3259–3267PubMedCrossRefPubMedCentralGoogle Scholar
  28. Limón ID et al (2011) Alteration of the sialylation pattern and memory deficits by injection of Aβ (25–35) into the hippocampus of rats. Neurosci Lett 495:11–16PubMedCrossRefPubMedCentralGoogle Scholar
  29. Majdi A, Sadigh-Eteghad S, Talebi M, Farajdokht F, Erfani M, Mahmoudi J, Gjedde A (2018) Nicotine modulates cognitive function in d-galactose-induced senescence in mice. Front Aging Neurosci.  https://doi.org/10.3389/fnagi.2018.00194 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631PubMedPubMedCentralCrossRefGoogle Scholar
  31. McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–122PubMedCrossRefPubMedCentralGoogle Scholar
  32. Medeiros LD, Vitor-de-Lima SM, Lira Benevides RD, do Egypto Queiroga RD, Araújo Guedes RC (2018) Neonatal administration of goat whey modulates memory and cortical spreading depression in rats previously suckled under different litter sizes: possible role of sialic acid. Nutr Neurosci 21:108–115PubMedCrossRefPubMedCentralGoogle Scholar
  33. Miglani S, Patyar RR, Patyar S, Reshi MR (2016) Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats. J Food Drug Anal 24:716–721PubMedCrossRefGoogle Scholar
  34. Nurliyani EH, Soesatyo M (2012) The effect of goat milk fractions supplementation on serum IgE response and leukocytes count in dinitrochlorobenzene sensitized rat. In: Paper presented at the Proceedings of World Academy of Science, Engineering and TechnologyGoogle Scholar
  35. Pal M et al (2017) Goat milk products and their significance. Beverage Food World 44:21–25Google Scholar
  36. Palombo JD, Ganguly A, Bistrian BR, Menard MP (2002) The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells. Cancer Lett 177:163–172PubMedCrossRefGoogle Scholar
  37. Park YW (2017) Goat milk—chemistry and nutrition. In: Park YW, Haenlein GFW, Wendorff WL (eds) Handbook of milk of non-bovine mammals. Wiley, Hoboken, pp 42–83CrossRefGoogle Scholar
  38. Park Y, Juárez M, Ramos M, Haenlein G (2007) Physico-chemical characteristics of goat and sheep milk. Small Rumin Res 68:88–113CrossRefGoogle Scholar
  39. Perovic M, Tesic V, Djordjevic AM, Smiljanic K, Loncarevic-Vasiljkovic N, Ruzdijic S, Kanazir S (2013) BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. Age 35:2057–2070PubMedCrossRefGoogle Scholar
  40. Qu Z, Zhang J, Yang H, Huo L, Gao J, Chen H, Gao W (2016) Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat. Physiol Behav 154:114–125PubMedCrossRefGoogle Scholar
  41. Rage F, Silhol M, Binamé F, Arancibia S, Tapia-Arancibia L (2007) Effect of aging on the expression of BDNF and TrkB isoforms in rat pituitary. Neurobiol Aging 28:1088–1098PubMedCrossRefPubMedCentralGoogle Scholar
  42. Rehman SU, Shah SA, Ali T, Chung JI, Kim MO (2017) Anthocyanins reversed d-galactose-induced oxidative stress and neuroinflammation mediated cognitive impairment in adult rats. Mol Neurobiol 54:255–271PubMedCrossRefPubMedCentralGoogle Scholar
  43. Rinaldi P et al (2003) Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 24:915–919PubMedCrossRefPubMedCentralGoogle Scholar
  44. Shen YX, Xu SY, Wei W, Sun XX, Yang J, Liu LH, Dong C (2002) Melatonin reduces memory changes and neural oxidative damage in mice treated with d-galactose. J Pineal Res 32:173–178PubMedCrossRefPubMedCentralGoogle Scholar
  45. Silanikove N, Leitner G, Merin U, Prosser C (2010) Recent advances in exploiting goat’s milk: quality, safety and production aspects. Small Rumin Res 89:110–124CrossRefGoogle Scholar
  46. Simos Y et al (2011) Antioxidant and anti-platelet properties of milk from goat, donkey and cow: an in vitro, ex vivo and in vivo study. Int Dairy J 21:901–906CrossRefGoogle Scholar
  47. Skaper SD (2012) The neurotrophin family of neurotrophic factors: an overview. In: Lewin G, Carter BD (eds) neurotrophic factors. Springer, Berlin, pp 1–12CrossRefGoogle Scholar
  48. Soares JK et al (2012) Conjugated linoleic acid in the maternal diet differentially enhances growth and cortical spreading depression in the rat progeny. Biochim Biophys Acta (BBA)-Gen Subj 1820:1490–1495CrossRefGoogle Scholar
  49. Torres LL et al (2011) Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 26:59–68PubMedCrossRefPubMedCentralGoogle Scholar
  50. Tu D-G, Chang Y-L, Chou C-H, Lin Y-L, Chiang C-C, Chang Y-Y, Chen Y-C (2018) Preventive effects of taurine against d-galactose-induced cognitive dysfunction and brain damage. Food Funct 9:124–133PubMedCrossRefPubMedCentralGoogle Scholar
  51. Wang B (2012) Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Adv Nutr 3:465S–472SPubMedPubMedCentralCrossRefGoogle Scholar
  52. Wang B et al (2007) Dietary sialic acid supplementation improves learning and memory in piglets. Am J Clin Nutr 85:561–569PubMedCrossRefPubMedCentralGoogle Scholar
  53. Wei H, Li L, Song Q, Ai H, Chu J, Li W (2005) Behavioural study of the D-galactose induced aging model in C57BL/6J mice. Behav Brain Res 157:245–251PubMedCrossRefPubMedCentralGoogle Scholar
  54. Woo J-Y, Gu W, Kim K-A, Jang S-E, Han MJ, Kim D-H (2014) Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a d-galactose-induced accelerated aging mouse model. Anaerobe 27:22–26PubMedCrossRefPubMedCentralGoogle Scholar
  55. Xian Y-F et al (2014) Isorhynchophylline improves learning and memory impairments induced by d-galactose in mice. Neurochem Int 76:42–49PubMedCrossRefPubMedCentralGoogle Scholar
  56. Xu M, Wei L, Dai Z, Zhang Y, Li Y, Wang J (2015) Effects of goat milk–based formula on development in weaned rats. Food Nutr Res 59:28610PubMedCrossRefPubMedCentralGoogle Scholar
  57. Yanar K et al (2011) Protein and DNA oxidation in different anatomic regions of rat brain in a mimetic ageing model. Basic Clin Physiol Pharmacol 109:423–433CrossRefGoogle Scholar
  58. Yoo DY et al (2012) Combination effects of sodium butyrate and pyridoxine treatment on cell proliferation and neuroblast differentiation in the dentate gyrus of d-galactose-induced aging model mice. Neurochem Res 37:223–231PubMedCrossRefPubMedCentralGoogle Scholar
  59. Zhang Q, Huang Y, Li X, Cui X, Zuo P, Li J (2005) GM1 ganglioside prevented the decline of hippocampal neurogenesis associated with d-galactose. Neuroreport 16:1297–1301PubMedCrossRefPubMedCentralGoogle Scholar
  60. Zhu J et al (2014) Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of d-galactose-induced aging. PLoS ONE 9:e101291PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Physiology, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia
  2. 2.School of Dental SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

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