Skip to main content Accessibility help
×
Home

Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring’s brain

  • Daniela P. Stocher (a1), Caroline P. Klein (a2), André B. Saccomori (a1), Pauline M. August (a2), Nicolli C. Martins (a1), Pablo R. G. Couto (a1), Martine E. K. Hagen (a3) and Cristiane Matté (a1) (a2)...

Abstract

Excessive salt intake is a common feature of Western dietary patterns, and has been associated with important metabolic changes including cerebral redox state imbalance. Considering that little is known about the effect on progeny of excessive salt intake during pregnancy, the present study investigated the effect of a high-salt diet during pregnancy and lactation on mitochondrial parameters and the redox state of the brains of resulting offspring. Adult female Wistar rats were divided into two dietary groups (n 20 rats/group): control standard chow (0·675 % NaCl) or high-salt chow (7·2 % NaCl), received throughout pregnancy and for 7 d after delivery. On postnatal day 7, the pups were euthanised and their cerebellum, hypothalamus, hippocampus, prefrontal and parietal cortices were dissected. Maternal high-salt diet reduced cerebellar mitochondrial mass and membrane potential, promoted an increase in reactive oxygen species allied to superoxide dismutase activation and decreased offspring cerebellar nitric oxide levels. A significant increase in hypothalamic nitric oxide levels and mitochondrial superoxide in the hippocampus and prefrontal cortex was observed in the maternal high-salt group. Antioxidant enzymes were differentially modulated by oxidant increases in each brain area studied. Taken together, our results suggest that a maternal high-salt diet during pregnancy and lactation programmes the brain metabolism of offspring, favouring impaired mitochondrial function and promoting an oxidative environment; this highlights the adverse effect of high-salt intake in the health state of the offspring.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring’s brain
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring’s brain
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring’s brain
      Available formats
      ×

Copyright

Corresponding author

* Corresponding author: C. Matté, fax +55 51 3308 5535, email matte@ufrgs.br

Footnotes

Hide All

These authors contributed equally to this work.

Footnotes

References

Hide All
1. Elliott, P & Brown, I (2006) Sodium Intakes Around the World. Background Document Prepared for the Forum and Technical Meeting on Reducing Salt Intake in Populations. Paris: France.
2. Powles, J, Fahimi, S, Micha, R, et al. (2013) Global, regional and national sodium intakes in 1990 and 2010: a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide. BMJ Open 3, e003733.
3. Intersalt (1988) Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ 297, 319328.
4. Mohan, S & Campbell, NR (2009) Salt and high blood pressure. Clin Sci (Lond) 117, 111.
5. Ito, T, Takeda, M, Hamano, T, et al. (2016) Effect of salt intake on blood pressure in patients receiving antihypertensive therapy: Shimane CoHRE Study. Eur J Intern Med 28, 7073.
6. Tuomilehto, J, Jousilahti, P, Rastenyte, D, et al. (2001) Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet 357, 848851.
7. Umesawa, M, Iso, H, Date, C, et al. (2008) Relations between dietary sodium and potassium intakes and mortality from cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of Cancer Risks. Am J Clin Nutr 88, 195202.
8. O’Donnell, MJ, Yusuf, S, Mente, A, et al. (2011) Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA 306, 22292238.
9. Tientcheu, D, Ayers, C, Das, SR, et al. (2015) Target organ complications and cardiovascular events associated with masked hypertension and white-coat hypertension: analysis from the Dallas Heart Study. J Am Coll Cardiol 66, 21592169.
10. Kisser, JE, Allen, AJ, Katzel, LI, et al. (2016) Relations of blood pressure and head injury to regional cerebral blood flow. J Neurol Sci 365, 914.
11. Meschia, JF, Bushnell, C, Boden-Albala, B, et al. (2014) Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45, 37543832.
12. Launer, LJ, Hughes, T, Yu, B, et al. (2010) Lowering midlife levels of systolic blood pressure as a public health strategy to reduce late-life dementia: perspective from the Honolulu Heart Program/Honolulu Asia Aging Study. Hypertension 55, 13521359.
13. Skoog, I & Gustafson, D (2006) Update on hypertension and Alzheimer’s disease. Neurol Res 28, 605611.
14. Paglieri, C, Bisbocci, D, Caserta, M, et al. (2008) Hypertension and cognitive function. Clin Exp Hypertens 30, 701710.
15. Korf, ES, White, LR, Scheltens, P, et al. (2004) Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia Aging Study. Hypertension 44, 2934.
16. Blaustein, MP, Zhang, J, Chen, L, et al. (2006) How does salt retention raise blood pressure? Am J Physiol Regul Integr Comp Physiol 290, R514R523.
17. DuPont, JJ, Greaney, JL, Wenner, MM, et al. (2013) High dietary sodium intake impairs endothelium-dependent dilation in healthy salt-resistant humans. J Hypertens 31, 530536.
18. Stocker, SD, Monahan, KD & Browning, KN (2013) Neurogenic and sympathoexcitatory actions of NaCl in hypertension. Curr Hypertens Rep 15, 538546.
19. O’Donnell, CJ & Elosua, R (2008) [Cardiovascular risk factors. Insights from Framingham Heart Study]. Rev Esp Cardiol 61, 299310.
20. Heijmans, BT, Tobi, EW, Stein, AD, et al. (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105, 1704617049.
21. Amaral, LM, Wallace, K, Owens, M, et al. (2017) Pathophysiology and current clinical management of preeclampsia. Curr Hypertens Rep 19, 61.
22. Staley, JR, Bradley, J, Silverwood, RJ, et al. (2015) Associations of blood pressure in pregnancy with offspring blood pressure trajectories during childhood and adolescence: findings from a prospective study. J Am Heart Assoc 4, e001422.
23. Miliku, K, Bergen, NE, Bakker, H, et al. (2016) Associations of maternal and paternal blood pressure patterns and hypertensive disorders during pregnancy with childhood blood pressure. J Am Heart Assoc 5, e003884.
24. Warshafsky, C, Pudwell, J, Walker, M, et al. (2016) Prospective assessment of neurodevelopment in children following a pregnancy complicated by severe pre-eclampsia. BMJ Open 6, e010884.
25. Zhang, S, Wang, L, Leng, J, et al. (2017) Hypertensive disorders of pregnancy in women with gestational diabetes mellitus on overweight status of their children. J Hum Hypertens 31, 731736.
26. Hales, CN & Barker, DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60, 520.
27. Morton, JS, Cooke, CL & Davidge, ST (2016) In utero origins of hypertension: mechanisms and targets for therapy. Physiol Rev 96, 549603.
28. Mathias, PC, Elmhiri, G, de Oliveira, JC, et al. (2014) Maternal diet, bioactive molecules, and exercising as reprogramming tools of metabolic programming. Eur J Nutr 53, 711722.
29. Bale, TL (2015) Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 16, 332344.
30. Canani, RB, Costanzo, MD, Leone, L, et al. (2011) Epigenetic mechanisms elicited by nutrition in early life. Nutr Res Rev 24, 198205.
31. Drenjančević-Perić, I, Jelaković, B, Lombard, JH, et al. (2011) High-salt diet and hypertension: focus on the renin-angiotensin system. Kidney Blood Press Res 34, 111.
32. Wu, H, Liang, Y, Zheng, Y, et al. (2014) Up-regulation of intrarenal renin-agiotensin system contributes to renal damage in high-salt induced hypertension rats. Kidney Blood Press Res 39, 526535.
33. Hayakawa, Y, Aoyama, T, Yokoyama, C, et al. (2015) High salt intake damages the heart through activation of cardiac (pro) renin receptors even at an early stage of hypertension. PLOS ONE 10, e0120453.
34. Liu, YZ, Chen, JK, Li, ZP, et al. (2014) High-salt diet enhances hippocampal oxidative stress and cognitive impairment in mice. Neurobiol Learn Mem 114, 1015.
35. Mayyas, F, Alzoubi, KH & Al-Taleb, Z (2017) Impact of high fat/high salt diet on myocardial oxidative stress. Clin Exp Hypertens 39, 126132.
36. Basgut, B, Whidden, MA, Kirichenko, N, et al. (2017) Effect of high-salt diet on age-related high blood pressure and hypothalamic redox signaling. Pharmacology 100, 105114.
37. Togliatto, G, Lombardo, G & Brizzi, MF (2017) The future challenge of reactive oxygen species (ROS) in hypertension: from bench to bed side. Int J Mol Sci 18, 19882004.
38. Ge, Q, Wang, Z, Wu, Y, et al. (2017) High salt diet impairs memory-related synaptic plasticity via increased oxidative stress and suppressed synaptic protein expression. Mol Nutr Food Res 61, 1700134.
39. Svitok, P, Molcan, L, Vesela, A, et al. (2015) Increased salt intake during early ontogenesis lead to development of arterial hypertension in salt-resistant Wistar rats. Clin Exp Hypertens 37, 142147.
40. Maruyama, K, Kagota, S, Van Vliet, BN, et al. (2015) A maternal high salt diet disturbs cardiac and vascular function of offspring. Life Sci 136, 4251.
41. Crnkovic, S, Riederer, M, Lechleitner, M, et al. (2012) Docosahexaenoic acid-induced unfolded protein response, cell cycle arrest, and apoptosis in vascular smooth muscle cells are triggered by Ca(2)(+)-dependent induction of oxidative stress. Free Radic Biol Med 52, 17861795.
42. Boveris, A (1984) Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. Methods Enzymol 105, 429435.
43. Aebi, H (1984) Catalase in vitro . Methods Enzymol 105, 121126.
44. Wendel, A (1981) Glutathione peroxidase. Methods Enzymol 77, 325333.
45. Browne, RW & Armstrong, D (1998) Reduced glutathione and glutathione disulfide. Methods Mol Biol 108, 347352.
46. Lowry, OH, Rosebrough, NJ, Farr, AL, et al. (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265275.
47. Tal, MC, Sasai, M, Lee, HK, et al. (2009) Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci U S A 106, 27702775.
48. Kalyanaraman, B, Darley-Usmar, V, Davies, KJ, et al. (2012) Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic Biol Med 52, 16.
49. World Health Organization (2007) World Health Organization Forum on Reducing Salt Intake in Populations: A Report of a WHO Forum and Technical Meeting . Paris: WHO.
50. Vishram, JK (2014) Prognostic interactions between cardiovascular risk factors. Dan Med J 61, B4892.
51. Cao, W, Li, A, Wang, L, et al. (2015) A salt-induced reno-cerebral reflex activates renin-Angiotensin systems and promotes CKD progression. J Am Soc Nephrol 26, 16191633.
52. Kalani, A, Pushpakumar, SB, Vacek, JC, et al. (2016) Inhibition of MMP-9 attenuates hypertensive cerebrovascular dysfunction in Dahl salt-sensitive rats. Mol Cell Biochem 413, 2535.
53. Fujita, M, Ando, K, Kawarazaki, H, et al. (2012) Sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in salt-induced chronic kidney disease. Hypertension 59, 105112.
54. Su, Q, Liu, JJ, Cui, W, et al. (2016) Alpha lipoic acid supplementation attenuates reactive oxygen species in hypothalamic paraventricular nucleus and sympathoexcitation in high salt-induced hypertension. Toxicol Lett 241, 152158.
55. Seravalli, P, de Oliveira, IB, Zago, BC, et al. (2016) High and low salt intake during pregnancy: impact on cardiac and renal structure in newborns. PLOS ONE 11, e0161598.
56. Ding, Y, Lv, J, Mao, C, et al. (2010) High-salt diet during pregnancy and angiotensin-related cardiac changes. J Hypertens 28, 12901297.
57. Reynolds, CM, Vickers, MH, Harrison, CJ, et al. (2014) High fat and/or high salt intake during pregnancy alters maternal meta-inflammation and offspring growth and metabolic profiles. Physiol Rep 2, e12110.
58. Gray, C, Al-Dujaili, EA, Sparrow, AJ, et al. (2013) Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling. PLOS ONE 8, e72682.
59. Piecha, G, Koleganova, N, Ritz, E, et al. (2012) High salt intake causes adverse fetal programming – vascular effects beyond blood pressure. Nephrol Dial Transplant 27, 34643476.
60. Da Silva, RC, de Souza, P & da Silva-Santos, JE (2016) Increased diuresis, renal vascular reactivity, and blood pressure levels in young rats fed high sodium, moderately high fructose, or their association: a comparative evaluation. Appl Physiol Nutr Metab 41, 12331239.
61. Pitynski-Miller, D, Ross, M, Schmill, M, et al. (2017) A high salt diet inhibits obesity and delays puberty in the female rat. Int J Obes (Lond) 41, 16851692.
62. Porter, JP, King, SH & Honeycutt, AD (2007) Prenatal high-salt diet in the Sprague-Dawley rat programs blood pressure and heart rate hyperresponsiveness to stress in adult female offspring. Am J Physiol Regul Integr Comp Physiol 293, R334R342.
63. Reynolds, CM, Vickers, MH, Harrison, CJ, et al. (2015) Maternal high fat and/or salt consumption induces sex-specific inflammatory and nutrient transport in the rat placenta. Physiol Rep 3, e12399.
64. Montezano, AC & Touyz, RM (2012) Molecular mechanisms of hypertension – reactive oxygen species and antioxidants: a basic science update for the clinician. Can J Cardiol 28, 288295.
65. Vassalle, C, Bianchi, S, Battaglia, D, et al. (2012) Elevated levels of oxidative stress as a prognostic predictor of major adverse cardiovascular events in patients with coronary artery disease. J Atheroscler Thromb 19, 712717.
66. Johnson, SA, Figueroa, A, Navaei, N, et al. (2015) Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial. J Acad Nutr Diet 115, 369377.
67. Montezano, AC, Dulak-Lis, M, Tsiropoulou, S, et al. (2015) Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol 31, 631641.
68. Rubattu, S, Pagliaro, B, Pierelli, G, et al. (2015) Pathogenesis of target organ damage in hypertension: role of mitochondrial oxidative stress. Int J Mol Sci 16, 823839.
69. Iadecola, C, Yaffe, K, Biller, J, et al. (2016) Impact of hypertension on cognitive function: a scientific statement from the American Heart Association. Hypertension 68, e67e94.
70. Qi, J, Yu, XJ, Shi, XL, et al. (2016) NF-kappaB blockade in hypothalamic paraventricular nucleus inhibits high-salt-induced hypertension through NLRP3 and caspase-1. Cardiovasc Toxicol 16, 345354.
71. Li, W, Lv, J, Wu, J, et al. (2016) Maternal high-salt diet altered PKC/MLC20 pathway and increased ANG II receptor-mediated vasoconstriction in adult male rat offspring. Mol Nutr Food Res 60, 16841694.
72. Mao, C, Liu, R, Bo, L, et al. (2013) High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system. J Endocrinol 218, 6173.
73. Marcelino, TB, Longoni, A, Kudo, KY, et al. (2013) Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats. Neuroscience 246, 2839.
74. Cheng, A, Hou, Y & Mattson, MP (2010) Mitochondria and neuroplasticity. ASN Neuro 2, e00045.
75. Uittenbogaard, M, Baxter, KK & Chiaramello, A (2010) The neurogenic basic helix-loop-helix transcription factor NeuroD6 confers tolerance to oxidative stress by triggering an antioxidant response and sustaining the mitochondrial biomass. ASN Neuro 2, e00034.
76. Wilkins, HM, Harris, JL, Carl, SM, et al. (2014) Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet 23, 65286541.
77. Michiels, C, Raes, M, Toussaint, O, et al. (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17, 235248.
78. Halliwell, B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35, 11471150.
79. Ribeiro, SMR, Queiroz, JH, Pelúzo, MCG, et al. (2005) A formação e os efeitos das espécies reativas de oxigênio no meio biológico (Formation and effects of reactive oxygen species in biological media). Biosci J 21, 133149.
80. Barreiros, ALBS & David, JM (2006) Estresse oxidativo: relação entre geração de espécies reativas e defesa do organismo (Oxidative stress: relations between the formation of reactive species and the organism’s defence). Quim Nova 29, 113123.
81. Rosselli, M, Keller, PJ & Dubey, RK (1998) Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 4, 324.
82. Chalimoniuk, M, Jagsz, S, Sadowska-Krepa, E, et al. (2015) Diversity of endurance training effects on antioxidant defenses and oxidative damage in different brain regions of adolescent male rats. J Physiol Pharmacol 66, 539547.
83. Katusic, ZS & Austin, SA (2016) Neurovascular protective function of endothelial nitric oxide- recent advances. Circ J 80, 14991503.
84. Roostaei, T, Nazeri, A, Sahraian, MA, et al. (2014) The human cerebellum: a review of physiologic neuroanatomy. Neurol Clin 32, 859869.
85. Koga, Y, Hirooka, Y, Araki, S, et al. (2008) High salt intake enhances blood pressure increase during development of hypertension via oxidative stress in rostral ventrolateral medulla of spontaneously hypertensive rats. Hypertens Res 31, 20752083.
86. Pacurari, M, Kafoury, R, Tchounwou, PB, et al. (2014) The renin-angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam 2014, 689360.
87. Wright, JW & Harding, JW (1994) Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. Neurosci Biobehav Rev 18, 2153.
88. Irigoyen, MC, Consolim-Colombo, FM & Krieger, EM (2001) Controle cardiovascular: regulação reflexa e papel do sistema nervoso simpático (Cardiovascular control: reflex regulation and role of the sympathetic nervous system). Rev Bras Hiperten 8, 5562.
89. Biancardi, VC, Son, SJ, Ahmadi, S, et al. (2014) Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier. Hypertension 63, 572579.
90. Mohammadi, MT & Dehghani, GA (2014) Acute hypertension induces brain injury and blood-brain barrier disruption through reduction of claudins mRNA expression in rat. Pathol Res Pract 210, 985990.
91. Zhang, T, Fang, S, Wan, C, et al. (2015) Excess salt exacerbates blood-brain barrier disruption via a p38/MAPK/SGK1-dependent pathway in permanent cerebral ischemia. Sci Rep 5, 16548.

Keywords

Type Description Title
PDF
Supplementary materials

Stocher et al. supplementary material
Figure S1

 PDF (16 KB)
16 KB
PDF
Supplementary materials

Stocher et al. supplementary material
Figure S2

 PDF (15 KB)
15 KB
PDF
Supplementary materials

Stocher et al. supplementary material
Figure S3

 PDF (21 KB)
21 KB
PDF
Supplementary materials

Stocher et al. supplementary material
Figure S4

 PDF (21 KB)
21 KB

Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring’s brain

  • Daniela P. Stocher (a1), Caroline P. Klein (a2), André B. Saccomori (a1), Pauline M. August (a2), Nicolli C. Martins (a1), Pablo R. G. Couto (a1), Martine E. K. Hagen (a3) and Cristiane Matté (a1) (a2)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.