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16.07.2020 | Original Article

A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats

verfasst von: Titikorn Chunchai, Puntarik Keawtep, Apiwan Arinno, Napatsorn Saiyasit, Dillon Prus, Nattayaporn Apaijai, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C. Chattipakorn

Erschienen in: Metabolic Brain Disease | Ausgabe 8/2020

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Abstract

Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a prebiotic and n-acetyl cysteine (NAC) improved cognitive dysfunction in obese rats and castrated-male rats. However, the effects of NAC, a prebiotic (inulin), and a combination of the two on cognition in castrated-obese rats has never been investigated. The hypothesis was that NAC and inulin attenuated cognitive decline in castrated-obese rats by improving gut dysbiosis, and decreasing oxidative stress, glial activation and apoptosis. Male Wistar rats (n = 36) were fed with either a normal diet (ND: n = 6) or a high-fat diet (HFD: n = 30) for twenty-eight weeks. The resultant obese rats had a bilateral orchiectomy (ORX) and were randomly divided into five subgroups (n = 6/ subgroup). Each subgroup was treated with one of five therapies: a vehicle; testosterone replacement (2 mg/kg/day); NAC (100 mg/kg); inulin (10%, w/w), or a combination of the NAC and inulin for four weeks. The results demonstrated that castrated-obese rats developed gut dysbiosis, metabolic disturbance, brain pathologies, and cognitive decline. All of the pathological conditions in the brain were ameliorated to an equal extent by testosterone replacement, NAC, and inulin supplementation. Interestingly, a combination of NAC and inulin had the greatest beneficial effect on cognitive function by synergistically reducing hippocampal inflammation and ameliorating glial dysmorphology. These findings suggest that a combination of NAC and inulin may confer the greatest benefits in improving cognitive function in castrated-obese male rats.

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Anastasovska J, Arora T, Sanchez Canon GJ, Parkinson JR, Touhy K, Gibson GR, Nadkarni NA, So PW, Goldstone AP, Thomas EL, Hankir MK, Van Loo J, Modi N, Bell JD, Frost G (2012) Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment. Obesity (Silver Spring) 20(5):1016–1023

Apaiajai N, Chunchai T, Jaiwongkam T, Kerdphoo S, Chattipakorn SC, Chattipakorn N (2018) Testosterone deprivation aggravates left-ventricular dysfunction in male obese insulin-resistant rats via impairing cardiac mitochondrial function and dynamics proteins. Gerontology 64(4):333–343PubMed

Arora T, Loo RL, Anastasovska J, Gibson GR, Tuohy KM, Sharma RK, Swann JR, Deaville ER, Sleeth ML, Thomas EL, Holmes E, Bell JD, Frost G (2012) Differential effects of two fermentable carbohydrates on central appetite regulation and body composition. PLoS One 7(8):e43263PubMedPubMedCentral

Atallah A, Mhaouty-Kodja S, Grange-Messent V (2017) Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice. J Cereb Blood Flow Metab 37(9):3161–3175PubMed

Bassil N, Morley JE (2010) Late-life onset hypogonadism: a review. Clin Geriatr Med 26(2):197–222PubMed

Bianchi VE (2019) The anti-inflammatory effects of testosterone. J Endocr Soc 3(1):91–107PubMed

Bobjer J, Katrinaki M, Tsatsanis C, Lundberg Giwercman Y, Giwercman A (2013) Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One 8(4):e61466PubMedPubMedCentral

Bocarsly ME, Fasolino M, Kane GA, LaMarca EA, Kirschen GW, Karatsoreos IN, McEwen BS, Gould E (2015) Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function. Proc Natl Acad Sci USA 112(51):15731–15736PubMedPubMedCentral

Bosland MC (2014) Testosterone treatment is a potent tumor promoter for the rat prostate. Endocrinology 155(12):4629–4633PubMedPubMedCentral

Buigues C, Fernandez-Garrido J, Pruimboom L, Hoogland AJ, Navarro-Martinez R, Martinez-Martinez M, Verdejo Y, Mascaros MC, Peris C, Cauli O (2016) Effect of a prebiotic formulation on frailty syndrome: a randomized, double-blind clinical trial. Int J Mol Sci 17(6)

Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772PubMed

Chunchai, T., Apaijai, N., Keawtep, P., Mantor, D., Arinno, A., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. C. (2018a). Testosterone deprivation intensifies cognitive decline in obese male rats via glial hyperactivity, increased oxidative stress, and apoptosis in both Hippocampus and cortex. Acta Physiol (Oxf): e13229

Chunchai T, Keawtep P, Arinno A, Saiyasit N, Prus D, Apaijai N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2019) N-acetyl cysteine, inulin and the two as a combined therapy ameliorate cognitive decline in testosterone-deprived rats. Aging (Albany NY) 11(11):3445–3462

Chunchai T, Samniang B, Sripetchwandee J, Pintana H, Pongkan W, Kumfu S, Shinlapawittayatorn K, KenKnight BH, Chattipakorn N, Chattipakorn SC (2016) Vagus nerve stimulation exerts the Neuroprotective effects in obese-insulin resistant rats, leading to the improvement of cognitive function. Sci Rep 6:26866PubMedPubMedCentral

Chunchai T, Thunapong W, Yasom S, Wanchai K, Eaimworawuthikul S, Metzler G, Lungkaphin A, Pongchaidecha A, Sirilun S, Chaiyasut C, Pratchayasakul W, Thiennimitr P, Chattipakorn N, Chattipakorn SC (2018b) Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. J Neuroinflammation 15(1):11PubMedPubMedCentral

Colldén H, Landin A, Wallenius V, Elebring E, Fändriks L, Nilsson ME, Ryberg H, Poutanen M, Sjögren K, Vandenput L, Ohlsson C (2019) The gut microbiota is a major regulator of androgen metabolism in intestinal contents. Am J Physiol Endocrinol Metab 317:E1182–E1192. https://doi.org/10.1152/ajpendo.00338.02019CrossRefPubMedPubMedCentral

Costa M, Bernardi J, Fiuza T, Costa L, Brandao R, Pereira ME (2016) N-acetylcysteine protects memory decline induced by streptozotocin in mice. Chem Biol Interact 253:10–17PubMed

Cryan JF, Dinan TG (2015) Gut microbiota: microbiota and neuroimmune signalling—Metchnikoff to microglia. Nat Rev Gastroenterol Hepatol 12(9):494–496PubMed

Dhindsa S, Ghanim H, Batra M, Kuhadiya ND, Abuaysheh S, Sandhu S, Green K, Makdissi A, Hejna J, Chaudhuri A, Punyanitya M, Dandona P (2016) Insulin resistance and inflammation in Hypogonadotropic Hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. Diabetes Care 39(1):82–91PubMed

Diniz YS, Rocha KK, Souza GA, Galhardi CM, Ebaid GM, Rodrigues HG, Novelli Filho JL, Cicogna AC, Novelli EL (2006) Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats. Eur J Pharmacol 543(1–3):151–157PubMed

Duan Y, An Y, Li N, Liu B, Wang Y, Tang H (2013) Multiple univariate data analysis reveals the inulin effects on the high-fat-diet induced metabolic alterations in rat myocardium and testicles in the preobesity state. J Proteome Res 12(7):3480–3495PubMed

Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V, Utermöhlen O, Chun E, Garrett WS, McCoy KD, Diefenbach A, Staeheli P, Stecher B, Amit I, Prinz M (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18(7):965–977PubMedPubMedCentral

Florowska A, Krygier K, Florowski T, Dluzewska E (2016) Prebiotics as functional food ingredients preventing diet-related diseases. Food Funct 7(5):2147–2155PubMed

Freeman LR, Haley-Zitlin V, Rosenberger DS, Granholm AC (2014) Damaging effects of a high-fat diet to the brain and cognition: a review of proposed mechanisms. Nutr Neurosci 17(6):241–251PubMed

Garcia-Ovejero D, Veiga S, Garcia-Segura LM, Doncarlos LL (2002) Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol 450(3):256–271PubMed

Gunther M, Davidsson J, Plantman S, Norgren S, Mathiesen T, Risling M (2015) Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats. J Clin Neurosci 22(9):1477–1483PubMed

Haring R, Baumeister SE, Volzke H, Dorr M, Kocher T, Nauck M, Wallaschofski H (2012) Prospective inverse associations of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress. J Androl 33(5):944–950PubMed

Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A, Matsumoto M, Kato D, Ono R, Kiyama H, Moorhouse AJ, Nabekura J, Wake H (2019) Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun 10(1):5816

Hatanaka Y, Hojo Y, Mukai H, Murakami G, Komatsuzaki Y, Kim J, Ikeda M, Hiragushi A, Kimoto T, Kawato S (2015) Rapid increase of spines by dihydrotestosterone and testosterone in hippocampal neurons: dependence on synaptic androgen receptor and kinase networks. Brain Res 1621:121–132PubMed

Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, Merry KM, Shi Q, Rosenthal A, Barres BA, Lemere CA, Selkoe DJ, Stevens B (2016) Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352(6286):712–716PubMedPubMedCentral

Hurley MM, Resch JM, Maunze B, Frenkel MM, Baker DA, Choi S (2016) N-acetylcysteine decreases binge eating in a rodent model. Int J Obes 40(7):1183–1186

Ji J, Maren S (2008) Differential roles for hippocampal areas CA1 and CA3 in the contextual encoding and retrieval of extinguished fear. Learn Mem 15(4):244–251

Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F (2010) Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol 73(5):602–612

Karalija A, Novikova LN, Kingham PJ, Wiberg M, Novikov LN (2014) The effects of N-acetyl-cysteine and acetyl-L-carnitine on neural survival, neuroinflammation and regeneration following spinal cord injury. Neuroscience 269:143–151PubMed

Keawtep P, Pratchayasakul W, Arinno A, Apaijai N, Chunchai T, Kerdphoo S, Jaiwongkum T, Chattipakorn N, Chattipakorn SC (2019) Combined dipeptidyl peptidase-4 inhibitor with low-dose testosterone exerts greater efficacy than monotherapy on improving brain function in orchiectomized obese rats. Exp Gerontol 123:45–56PubMed

Kettenmann H, Kirchhoff F, Verkhratsky A (2013) Microglia: new roles for the synaptic stripper. Neuron 77(1):10–18PubMed

Lee KY, Chung K, Chung JM (2010) Involvement of reactive oxygen species in long-term potentiation in the spinal cord dorsal horn. J Neurophysiol 103(1):382–391PubMed

Leranth C, Petnehazy O, MacLusky NJ (2003) Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. J Neurosci 23(5):1588–1592PubMedPubMedCentral

Li M, Masugi-Tokita M, Takanami K, Yamada S, Kawata M (2012) Testosterone has sublayer-specific effects on dendritic spine maturation mediated by BDNF and PSD-95 in pyramidal neurons in the hippocampus CA1 area. Brain Res 1484:76–84PubMed

Liu TW, Cephas KD, Holscher HD, Kerr KR, Mangian HF, Tappenden KA, Swanson KS (2016) Nondigestible Fructans Alter gastrointestinal barrier function, gene expression, Histomorphology, and the microbiota profiles of diet-induced obese C57BL/6J mice. J Nutr 146(5):949–956PubMed

Ma Y, Gao M, Liu D (2016) N-acetylcysteine protects mice from high fat diet-induced metabolic disorders. Pharm Res 33(8):2033–2042PubMedPubMedCentral

MacLusky NJ, Hajszan T, Prange-Kiel J, Leranth C (2006) Androgen modulation of hippocampal synaptic plasticity. Neuroscience 138(3):957–965PubMed

Massaad CA, Klann E (2011) Reactive oxygen species in the regulation of synaptic plasticity and memory. Antioxid Redox Signal 14(10):2013–2054PubMedPubMedCentral

Messaoudi M, Rozan P, Nejdi A, Hidalgo S, Desor D (2007) Behavioural and cognitive effects of oligofructose-enriched inulin in rats. Br J Nutr 93(S1):S27

Muraleedharan V, Jones TH (2010) Testosterone and the metabolic syndrome. Ther Adv Endocrinol Metab 1(5):207–223PubMedPubMedCentral

Parnell JA, Reimer RA (2012) Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats. Br J Nutr 107(4):601–613PubMed

Pintana H, Pongkan W, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2015) Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress. Age (Dordr) 37(5):84

Pintana H, Pratchayasakul W, Sa-Nguanmoo P, Pongkan W, Tawinvisan R, Chattipakorn N, Chattipakorn SC (2016a) Testosterone deprivation has neither additive nor synergistic effects with obesity on the cognitive impairment in orchiectomized and/or obese male rats. Metabolism 65(2):54–67PubMed

Pintana H, Pratchayasakul W, Sa-nguanmoo P, Pongkan W, Tawinvisan R, Chattipakorn N, Chattipakorn SC (2016b) Testosterone deprivation has neither additive nor synergistic effects with obesity on the cognitive impairment in orchiectomized and/or obese male rats. Metabolism 65(2):54–67PubMed

Pongkan W, Pintana H, Sivasinprasan S, Jaiwongkam T, Chattipakorn S, Chattipakorn N (2016) Testosterone deprivation accelerates cardiac dysfunction in obese male rats. J Endocrinol (in press) 229:209–220PubMed

Prakash A, Kalra JK, Kumar A (2015) Neuroprotective effect of N-acetyl cysteine against streptozotocin-induced memory dysfunction and oxidative damage in rats. J Basic Clin Physiol Pharmacol 26(1):13–23PubMed

Pratchayasakul W, Kerdphoo S, Petsophonsakul P, Pongchaidecha A, Chattipakorn N, Chattipakorn SC (2011) Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone. Life Sci 88(13–14):619–627PubMed

Pratchayasakul W, Sa-Nguanmoo P, Sivasinprasasn S, Pintana H, Tawinvisan R, Sripetchwandee J, Kumfu S, Chattipakorn N, Chattipakorn SC (2015) Obesity accelerates cognitive decline by aggravating mitochondrial dysfunction, insulin resistance and synaptic dysfunction under estrogen-deprived conditions. Horm Behav 72:68–77PubMed

Reimer RA, Russell JC (2008) Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet. Obesity (Silver Spring) 16(1):40–46

Romeo RD, Staub D, Jasnow AM, Karatsoreos IN, Thornton JE, McEwen BS (2005) Dihydrotestosterone increases hippocampal N-methyl-D-aspartate binding but does not affect choline acetyltransferase cell number in the forebrain or choline transporter levels in the CA1 region of adult male rats. Endocrinology 146(4):2091–2097PubMed

Ruiz-Ruiz, S., Sanchez-Carrillo, S., Ciordia, S., Mena, M. C., Méndez-García, C., Rojo, D., Bargiela, R., Zubeldia-Varela, E., Martínez-Martínez, M., Barbas, C., Ferrer, M., & Moya, A. (2019). Functional microbiome deficits associated with ageing: chronological age threshold. Aging cell: e13063-e13063

Sa-Nguanmoo P, Tanajak P, Kerdphoo S, Satjaritanun P, Wang X, Liang G, Li X, Jiang C, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2016) FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats. Horm Behav 85:86–95PubMed

Shin J-H, Park Y-H, Sim M, Kim S-A, Joung H, Shin D-M (2019) Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res Microbiol 170(4–5):192–201PubMed

Skvarc DR, Dean OM, Byrne LK, Gray L, Lane S, Lewis M, Fernandes BS, Berk M, Marriott A (2017) The effect of N-acetylcysteine (NAC) on human cognition - a systematic review. Neurosci Biobehav Rev 78:44–56PubMed

Smith AP, Sutherland D, Hewlett P (2015) An investigation of the acute effects of Oligofructose-enriched inulin on subjective wellbeing, mood and cognitive performance. Nutrients 7(11):8887–8896PubMedPubMedCentral

Soisson V, Brailly-Tabard S, Helmer C, Rouaud O, Ancelin ML, Zerhouni C, Guiochon-Mantel A, Scarabin PY (2013) A J-shaped association between plasma testosterone and risk of ischemic arterial event in elderly men: the French 3C cohort study. Maturitas 75(3):282–288PubMed

Thiennimitr P, Yasom S, Tunapong W, Chunchai T, Wanchai K, Pongchaidecha A, Lungkaphin A, Sirilun S, Chaiyasut C, Chattipakorn N, Chattipakorn SC (2018) Lactobacillus paracasei HII01, xylooligosaccharides, and synbiotics reduce gut disturbance in obese rats. Nutrition 54:40–47PubMed

Traish AM, Morgentaler A, Khera M (2015) RE: testosterone treatment is a potent tumor promoter for the rat prostate. Endocrinology 156(1):L1–L2PubMed

Tsai GY, Cui JZ, Syed H, Xia Z, Ozerdem U, McNeill JH, Matsubara JA (2009) Effect of N-acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats. Clin Exp Ophthalmol 37(2):223–231PubMedPubMedCentral

Tunapong, W., Apaijai, N., Yasom, S., Tanajak, P., Wanchai, K., Chunchai, T., Kerdphoo, S., Eaimworawuthikul, S., Thiennimitr, P., Pongchaidecha, A., Lungkaphin, A., Pratchayasakul, W., Chattipakorn, S. C., & Chattipakorn, N. (2017). Chronic treatment with prebiotics, probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats. Eur J Nutr

Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858PubMedPubMedCentral

Winter SE, Thiennimitr P, Winter MG, Butler BP, Huseby DL, Crawford RW, Russell JM, Bevins CL, Adams LG, Tsolis RM, Roth JR, Baumler AJ (2010) Gut inflammation provides a respiratory electron acceptor for salmonella. Nature 467(7314):426–429PubMedPubMedCentral

Titel: A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats
verfasst von: Titikorn Chunchai
Puntarik Keawtep
Apiwan Arinno
Napatsorn Saiyasit
Dillon Prus
Nattayaporn Apaijai
Wasana Pratchayasakul
Nipon Chattipakorn
Siriporn C. Chattipakorn
Publikationsdatum: 16.07.2020
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 8/2020
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-020-00603-5

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A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats

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