Maternal Dietary Deficiency in Choline Reduced Levels of MMP-2 Levels in Blood and Brain Tissue of Male Offspring Mice

Overview

Journal bioRxiv

Date 2024 Jul 29

PMID 39071273

Authors

Mitra Esfandiarei

Shawn G U Strash

Amanda Covaleski

Sharadyn Ille

Weidang Li

Nafisa M Jadavji

Affiliations

Soon will be listed here.

Abstract

Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. It's well known that maternal diet during pregnancy and lactation is vital for the early neurodevelopment of offspring. One-carbon (1C) metabolism, including folic acid and choline, plays a vital role in closure of the neural tube . However, the impact of maternal dietary deficiencies in 1C on offspring neurological function following ischemic stroke later in life remains undefined. The aim of this study was to investigate inflammation in blood and brain tissue of offspring from mothers deficient in dietary folic acid or choline. Female mice were maintained on either a control or deficient diets prior to and during pregnancy and lactation. When offspring were 3-months of age, ischemic stroke was induced. One and half months later blood and brain tissue were collected. We measured levels of matrix-metalloproteases (MMP)-2 and 9 in both plasma and brain tissue, and report reduced levels of MMP-2 in both, with no changes observed in MMP-9. This observation supports our working hypothesis that maternal dietary deficiencies in folic acid or choline during early neurodevelopment impact the levels of inflammation in offspring after ischemic stroke.

References

Campbell B, Khatri P . Stroke. Lancet. 2020; 396(10244):129-142. DOI: 10.1016/S0140-6736(20)31179-X. View

Mills K, Stefanescu A, He J . The global epidemiology of hypertension. Nat Rev Nephrol. 2020; 16(4):223-237. PMC: 7998524. DOI: 10.1038/s41581-019-0244-2. View

Georgieff M, Ramel S, Cusick S . Nutritional influences on brain development. Acta Paediatr. 2018; 107(8):1310-1321. PMC: 6045434. DOI: 10.1111/apa.14287. View

Jadavji N, Farr T, Lips J, Khalil A, Boehm-Sturm P, Foddis M . Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. Behav Brain Res. 2015; 283:215-26. DOI: 10.1016/j.bbr.2015.01.040. View

Hankey G . B vitamins for stroke prevention. Stroke Vasc Neurol. 2018; 3(2):51-58. PMC: 6047336. DOI: 10.1136/svn-2018-000156. View

Yahn G, Abato J, Jadavji N . Role of vitamin B12 deficiency in ischemic stroke risk and outcome. Neural Regen Res. 2020; 16(3):470-474. PMC: 7996019. DOI: 10.4103/1673-5374.291381. View

Clare C, Brassington A, Kwong W, Sinclair K . One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development. Annu Rev Anim Biosci. 2018; 7:263-287. DOI: 10.1146/annurev-animal-020518-115206. View

Barker D, Gluckman P, Godfrey K, Harding J, Owens J, Robinson J . Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341(8850):938-41. DOI: 10.1016/0140-6736(93)91224-a. View

Georgieff M . Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr. 2007; 85(2):614S-620S. DOI: 10.1093/ajcn/85.2.614S. View

10.

Tejima E, Guo S, Murata Y, Arai K, Lok J, van Leyen K . Neuroprotective effects of overexpressing tissue inhibitor of metalloproteinase TIMP-1. J Neurotrauma. 2009; 26(11):1935-41. PMC: 2822804. DOI: 10.1089/neu.2009.0959. View

11.

Jadavji N, Emmerson J, MacFarlane A, Willmore W, Smith P . B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiol Dis. 2017; 103:89-100. DOI: 10.1016/j.nbd.2017.04.001. View

12.

Mbs G, Wasek B, Bottiglieri T, Malysheva O, Caudill M, Jadavji N . Dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke in middle-aged male and female mice. Nutr Neurosci. 2023; 27(4):300-309. DOI: 10.1080/1028415X.2023.2188639. View

13.

Loffek S, Schilling O, Franzke C . Series "matrix metalloproteinases in lung health and disease": Biological role of matrix metalloproteinases: a critical balance. Eur Respir J. 2010; 38(1):191-208. DOI: 10.1183/09031936.00146510. View

14.

Owolabi U, Amraotkar A, Coulter A, Singam N, Aladili B, Singh A . Change in matrix metalloproteinase 2, 3, and 9 levels at the time of and after acute atherothrombotic myocardial infarction. J Thromb Thrombolysis. 2019; 49(2):235-244. PMC: 9012982. DOI: 10.1007/s11239-019-02004-7. View

15.

Aslam A, Misbah S, Talbot K, Chapel H . Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Clin Immunol. 2004; 112(1):24-9. DOI: 10.1016/j.clim.2004.02.001. View

16.

Prust M, Forman R, Ovbiagele B . Addressing disparities in the global epidemiology of stroke. Nat Rev Neurol. 2024; 20(4):207-221. DOI: 10.1038/s41582-023-00921-z. View

17.

Zeisel S . Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr. 2006; 26:229-50. PMC: 2441939. DOI: 10.1146/annurev.nutr.26.061505.111156. View

18.

Reeves P, Nielsen F, Fahey Jr G . AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993; 123(11):1939-51. DOI: 10.1093/jn/123.11.1939. View

19.

Barker D . Intrauterine programming of coronary heart disease and stroke. Acta Paediatr Suppl. 1997; 423:178-82; discussion 183. DOI: 10.1111/j.1651-2227.1997.tb18408.x. View

20.

Nyaradi A, Li J, Hickling S, Foster J, Oddy W . The role of nutrition in children's neurocognitive development, from pregnancy through childhood. Front Hum Neurosci. 2013; 7:97. PMC: 3607807. DOI: 10.3389/fnhum.2013.00097. View