Maternal Obesity and Developmental Programming of Neuropsychiatric Disorders: An Inflammatory Hypothesis

Overview

Journal Brain Neurosci Adv

Publisher Sage Publications

Specialty Neurology

Date 2021 Apr 23

PMID 33889757

Citations 15

Authors

Jonathan Davis

Erik Mire

Affiliations

Soon will be listed here.

Abstract

Maternal obesity is associated with the development of a variety of neuropsychiatric disorders; however, the mechanisms behind this association are not fully understood. Comparison between maternal immune activation and maternal obesity reveals similarities in associated impairments and maternal cytokine profile. Here, we present a summary of recent evidence describing how inflammatory processes contribute towards the development of neuropsychiatric disorders in the offspring of obese mothers. This includes discussion on how maternal cytokine levels, fatty acids and placental inflammation may interact with foetal neurodevelopment through changes to microglial behaviour and epigenetic modification. We also propose an exosome-mediated mechanism for the disruption of brain development under maternal obesity and discuss potential intervention strategies.

Citing Articles

Maternal Obesity and Neurodevelopment of the Offspring.

Eleftheriades A, Koulouraki S, Belegrinos A, Eleftheriades M, Pervanidou P Nutrients. 2025; 17(5).

PMID: 40077761 PMC: 11901708. DOI: 10.3390/nu17050891.

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity.

Batorsky R, Ceasrine A, Shook L, Kislal S, Bordt E, Devlin B Cell Rep. 2024; 43(6):114326.

PMID: 38848212 PMC: 11808824. DOI: 10.1016/j.celrep.2024.114326.

When autophagy meets placenta development and pregnancy complications.

Zhou P, Wang J, Wang J, Liu X Front Cell Dev Biol. 2024; 12:1327167.

PMID: 38371923 PMC: 10869551. DOI: 10.3389/fcell.2024.1327167.

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity.

Batorsky R, Ceasrine A, Shook L, Kislal S, Bordt E, Devlin B bioRxiv. 2024; .

PMID: 38187648 PMC: 10769274. DOI: 10.1101/2023.12.16.571680.

Maternal Thyroid Dysfunction During Pregnancy as an Etiologic Factor in Autism Spectrum Disorder: Challenges and Opportunities for Research.

Kaplan Z, Pearce E, Lee S, Shin H, Schmidt R Thyroid. 2023; 34(2):144-157.

PMID: 38149625 PMC: 10884547. DOI: 10.1089/thy.2023.0391.

References

Luo S, Timbang L, Kim J, Shang Y, Sandoval K, Tang A . TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning. Cell Rep. 2016; 17(12):3233-3245. PMC: 5312261. DOI: 10.1016/j.celrep.2016.11.068. View

Holder B, Jones T, Sancho Shimizu V, Rice T, Donaldson B, Bouqueau M . Macrophage Exosomes Induce Placental Inflammatory Cytokines: A Novel Mode of Maternal-Placental Messaging. Traffic. 2015; 17(2):168-78. PMC: 4738478. DOI: 10.1111/tra.12352. View

Benaim C, Freitas-Vilela A, Pinto T, Lepsch J, Farias D, Vaz J . Early pregnancy body mass index modifies the association of pre-pregnancy dietary patterns with serum polyunsaturated fatty acid concentrations throughout pregnancy in Brazilian women. Matern Child Nutr. 2017; 14(1). PMC: 6866055. DOI: 10.1111/mcn.12480. View

Abuaish S, Spinieli R, McGowan P . Perinatal high fat diet induces early activation of endocrine stress responsivity and anxiety-like behavior in neonates. Psychoneuroendocrinology. 2018; 98:11-21. DOI: 10.1016/j.psyneuen.2018.08.003. View

Sheller-Miller S, Choi K, Choi C, Menon R . Cyclic-recombinase-reporter mouse model to determine exosome communication and function during pregnancy. Am J Obstet Gynecol. 2019; 221(5):502.e1-502.e12. DOI: 10.1016/j.ajog.2019.06.010. View

Zhou W, Woodson M, Sherman M, Neelakanta G, Sultana H . Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons. Emerg Microbes Infect. 2019; 8(1):307-326. PMC: 6455149. DOI: 10.1080/22221751.2019.1578188. View

Buffington S, Di Prisco G, Auchtung T, Ajami N, Petrosino J, Costa-Mattioli M . Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016; 165(7):1762-1775. PMC: 5102250. DOI: 10.1016/j.cell.2016.06.001. View

Yockey L, Iwasaki A . Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development. Immunity. 2018; 49(3):397-412. PMC: 6152841. DOI: 10.1016/j.immuni.2018.07.017. View

Yang X, Haghiac M, Glazebrook P, Minium J, Catalano P, Hauguel-De Mouzon S . Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts. Hum Reprod. 2015; 30(9):2152-9. PMC: 4635648. DOI: 10.1093/humrep/dev173. View

10.

Sharma P, Schiapparelli L, Cline H . Exosomes function in cell-cell communication during brain circuit development. Curr Opin Neurobiol. 2013; 23(6):997-1004. PMC: 3830597. DOI: 10.1016/j.conb.2013.08.005. View

11.

Iraci N, Leonardi T, Gessler F, Vega B, Pluchino S . Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles. Int J Mol Sci. 2016; 17(2):171. PMC: 4783905. DOI: 10.3390/ijms17020171. View

12.

Thomou T, Mori M, Dreyfuss J, Konishi M, Sakaguchi M, Wolfrum C . Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017; 542(7642):450-455. PMC: 5330251. DOI: 10.1038/nature21365. View

13.

Zhang Z, Li Z, Yuan S . The Role of Secretory Autophagy in Zika Virus Transfer through the Placental Barrier. Front Cell Infect Microbiol. 2017; 6:206. PMC: 5220013. DOI: 10.3389/fcimb.2016.00206. View

14.

Maldonado-Ruiz R, Garza-Ocanas L, Camacho A . Inflammatory domains modulate autism spectrum disorder susceptibility during maternal nutritional programming. Neurochem Int. 2019; 126:109-117. DOI: 10.1016/j.neuint.2019.03.009. View

15.

Glass R, Norton S, Fox N, Kusnecov A . Maternal immune activation with staphylococcal enterotoxin A produces unique behavioral changes in C57BL/6 mouse offspring. Brain Behav Immun. 2018; 75:12-25. DOI: 10.1016/j.bbi.2018.05.005. View

16.

Yao Q, Liu J, Xiao L, Wang N . Sonic hedgehog signaling instigates high-fat diet-induced insulin resistance by targeting PPARγ stability. J Biol Chem. 2018; 294(9):3284-3293. PMC: 6398147. DOI: 10.1074/jbc.RA118.004411. View

17.

Mitsuya K, Parker A, Liu L, Ruan J, Vissers M, Myatt L . Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation. PLoS One. 2017; 12(10):e0186115. PMC: 5646778. DOI: 10.1371/journal.pone.0186115. View

18.

Frydecka D, Misiak B, Beszlej J, Karabon L, Pawlak-Adamska E, Tomkiewicz A . Genetic variants in transforming growth factor-β gene (TGFB1) affect susceptibility to schizophrenia. Mol Biol Rep. 2013; 40(10):5607-14. PMC: 3824289. DOI: 10.1007/s11033-013-2662-8. View

19.

Vento-Tormo R, Efremova M, Botting R, Turco M, Vento-Tormo M, Meyer K . Single-cell reconstruction of the early maternal-fetal interface in humans. Nature. 2018; 563(7731):347-353. PMC: 7612850. DOI: 10.1038/s41586-018-0698-6. View

20.

Amoli M, Khatami F, Arzaghi S, Enayati S, Nejatisafa A . Over-expression of TGF-β1 gene in medication free Schizophrenia. Psychoneuroendocrinology. 2018; 99:265-270. DOI: 10.1016/j.psyneuen.2018.10.009. View