CoChat
Sign Up
Cited by 85Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersBirth, Development, and Health

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Open access
Bordeleau, Maude, Lacabanne, Chloé, Fernández de Cossío, Lourdes, Vernoux, Nathalie, Savage, Julie C., González-Ibáñez, Fernando, Tremblay, Marie-Ève·2020·Journal of Neuroinflammation
DOI 10.1186/s12974-020-01914-1PMC PMC7487673

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Maternal nutrition is critical for proper fetal development. While increased nutrient intake is essential during pregnancy, an excessive consumption of certain nutrients, like fat, can lead to long-lasting detrimental consequences on the offspring. Animal work investigating the consequences of maternal high-fat diet (mHFD) revealed in the offspring a maternal immune activation (MIA) phenotype associated with increased inflammatory signals. This inflammation was proposed as one of the mechanisms causing neuronal circuit dysfunction, notably in the hippocampus, by altering the brain-resident macrophages—microglia. However, the understanding of mechanisms linking inflammation and microglial activities to pathological brain development remains limited. We hypothesized that mHFD-induced inflammation could prime microglia by altering their specific gene expression signature, population density, and/or functions. Methods: We used an integrative approach combining molecular (i.e., multiplex-ELISA, rt-qPCR) and cellular (i.e., histochemistry, electron microscopy) techniques to investigate the effects of mHFD (saturated and unsaturated fats) vs control diet on inflammatory priming, as well as microglial transcriptomic signature, density, distribution, morphology, and ultrastructure in mice. These analyses were performed on the mothers and/or their adolescent offspring at postnatal day 30. Results: Our study revealed that mHFD results in MIA defined by increased circulating levels of interleukin (IL)-6 in the mothers. This phenotype was associated with an exacerbated inflammatory response to peripheral lipopolysaccharide in mHFD-exposed offspring of both sexes. Microglial morphology was also altered, and there were increased microglial interactions with astrocytes in the hippocampus CA1 of mHFD-exposed male offspring, as well as decreased microglia-associated extracellular space pockets in the same region of mHFD-exposed offspring of the two sexes. A decreased mRNA expression of the inflammatory-regulating cytokine Tgfb1 and microglial receptors Tmem119 , Trem2 , and Cx3cr1 was additionally measured in the hippocampus of mHFD-exposed offspring, especially in males . Conclusions: Here, we described how dietary habits during pregnancy and nurturing, particularly the consumption of an enriched fat diet, can influence peripheral immune priming in the offspring. We also found that microglia are affected in terms of gene expression signature, morphology, and interactions with the hippocampal parenchyma, in a partially sexually dimorphic manner, which may contribute to the adverse neurodevelopmental outcomes on the offspring.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12974-020-01914-1

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Microglia are highly affected by sex hormones.

    “Microglia, which are the resident innate immune cells of the CNS, are highly affected by sex hormones [14, 16–20].”

    From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [16]

    The Discussion (page unavailable) says neuroendocrine receptors can modulate microglial functions and that microglia express these receptors differently between sexes. That supports hormonal regulation and sex-related differences, but it does not establish that sex hormones specifically have a strong effect on microglia. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Few other studies have shown sex-specific differences in microglia between regions and layers of the hippocampus.

    “Few other studies have shown sex-specific differences in microglia between regions and layers of the hippocampus [16, 56–58]”

    From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [16]

    The Results section on microglial interactions reports a sex difference in neuronal contacts in the CA1 stratum lacunosum-moleculare and a male-specific response to maternal high-fat diet in two CA1 layers. The study examined those layers within CA1; it does not establish sex-specific differences between distinct hippocampal regions. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 99

  1. [1]Bolton JL Bilbo SD Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms Dialogues Clin Neurosci 2014 16 307 320 25364282 PMC4214174
  2. [2]Sullivan EL Riper KM Lockard R Valleau JC Maternal high-fat diet programming of the neuroendocrine system and behavior Horm Behav 2015 76 153 161 25913366 PMC4619177
  3. [3]Mina TH Lahti M Drake AJ Räikkönen K Minnis H Denison FC Prenatal exposure to very severe maternal obesity is associated with adverse neuropsychiatric outcomes in children Psychol Med 2017 47 353 362 27776561
  4. [4]Chen C Xu X Yan Y Estimated global overweight and obesity burden in pregnant women based on panel data model PLoS One 2018 13 e0202183 30092099 PMC6084991
  5. [6]Hariri N Thibault L High-fat diet-induced obesity in animal models Nutr Res Rev 2010 23 270 299 20977819
  6. [7]Sauerwald TU Demmelmair H Koletzko B Polyunsaturated fatty acid supply with human milk Lipids. 2001 36 991 996 11724472
  7. [8]Bilbo SD Tsang V Enduring consequences of maternal obesity for brain inflammation and behavior of offspring FASEB J 2010 24 2104 2115 20124437
  8. [9]Thompson JR Gustafsson HC DeCapo M Takahashi DL Bagley JL Dean TA Maternal diet, metabolic state, and inflammatory response exert unique and long-lasting influences on offspring behavior in non-human primates Front Endocrinol 2018 9 161 PMC5924963 29740395
  9. [10]Winther G Elfving B Müller HK Lund S Wegener G Maternal high-fat diet programs offspring emotional behavior in adulthood Neuroscience. 2018 388 87 101 30025860
  10. [11]Sullivan EL Grayson B Takahashi D Robertson N Maier A Bethea CL Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring J Neurosci 2010 30 3826 3830 20220017 PMC2846411
  11. [13]Sasaki A de Vega WC St-Cyr S Pan P McGowan PO Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood Neuroscience. 2013 240 1 12 23454542
  12. [14]Graf AE Lallier SW Waidyaratne G Thompson MD Tipple TE Hester ME Maternal high fat diet exposure is associated with increased hepcidin levels, decreased myelination, and neurobehavioral changes in male offspring Brain Behav Immun 2016 58 369 378 27519153 PMC5611850
  13. [15]Cordner ZA Khambadkone SG Boersma GJ Song L Summers TN Moran TH Maternal high-fat diet results in cognitive impairment and hippocampal gene expression changes in rat offspring Exp Neurol 2019 318 92 31051155 PMC6588424
  14. [16]Tozuka Y Kumon M Wada E Onodera M Mochizuki H Wada K Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring Neurochem Int 2010 57 235 247 20538025
  15. [17]Grissom NM Herdt CT Desilets J Lidsky-Everson J Reyes TM Dissociable deficits of executive function caused by gestational adversity are linked to specific transcriptional changes in the prefrontal cortex Neuropsychopharmacology. 2015 40 1353 1363 25418810 PMC4397392
  16. [18]Smith BL Laaker CJ Lloyd KR Hiltz AR Reyes TM Adolescent microglia play a role in executive function in male mice exposed to perinatal high fat diet Brain Behav Immun 2019 84 80 89 31765789 PMC8634520
  17. [19]Meyer U Feldon J Fatemi SH In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders Neurosci Biobehav Rev 2009 33 1061 1079 19442688
  18. [21]Brucato M Ladd-Acosta C Li M Caruso D Hong X Kaczaniuk J Prenatal exposure to fever is associated with autism spectrum disorder in the Boston birth cohort Autism Res Off J Int Soc Autism Res 2017 10 1878 1890 PMC5685874 28799289
  19. [22]Bilbo SD Block CL Bolton JL Hanamsagar R Tran PK Beyond infection - maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders Exp Neurol 2018 299 241 251 28698032 PMC5723548
  20. [23]Feigenson KA Kusnecov AW Silverstein SM Inflammation and the two-hit hypothesis of schizophrenia Neurosci Biobehav Rev 2014 38 72 93 24247023 PMC3896922
  21. [24]Delpech J-C Wei L Hao J Yu X Madore C Butovsky O Early life stress perturbs the maturation of microglia in the developing hippocampus Brain Behav Immun 2016 57 79 93 27301858 PMC5010940
  22. [25]Rincel M, Lépinay AL, Janthakhin Y, Soudain G, Yvon S, Silva SD, et al. Maternal high-fat diet and early life stress differentially modulate spine density and dendritic morphology in the medial prefrontal cortex of juvenile and adult rats. Brain Struct Funct. 2017:1–13. 29022091
  23. [27]Proietti E Röösli M Frey U Latzin P Air pollution during pregnancy and neonatal outcome: a review J Aerosol Med Pulm Drug Deliv 2012 26 9 23 22856675
  24. [28]Bolton JL Auten RL Bilbo SD Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring Brain Behav Immun 2014 37 30 44 24184474
  25. [29]Knuesel I Chicha L Britschgi M Schobel SA Bodmer M Hellings JA Maternal immune activation and abnormal brain development across CNS disorders Nat Rev Neurol 2014 10 643 660 25311587
  26. [31]van Kesteren CFMG Gremmels H de Witte LD Hol EM Van Gool AR Falkai PG Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies Transl Psychiatry 2017 7 e1075 28350400 PMC5404615
  27. [32]Sasaki A de Vega W Sivanathan S St-Cyr S McGowan PO Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring Neuroscience. 2014 272 92 101 24791714
  28. [33]Schwarz JM Bilbo SD Sex, glia, and development: interactions in health and disease Horm Behav 2012 62 243 253 22387107 PMC3374064
  29. [34]Hanamsagar R Bilbo SD Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development J Steroid Biochem Mol Biol 2016 160 127 133 26435451 PMC4829467
  30. [35]Bordeleau M Carrier M Luheshi GN Tremblay M-È Microglia along sex lines: from brain colonization, maturation and function, to implication in neurodevelopmental disorders Semin Cell Dev Biol 2019 94 152 163 31201858
  31. [37]Domingues HS Portugal CC Socodato R Relvas JB Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair Front Cell Dev Biol 2016 4 71 27551677 PMC4923166
  32. [38]Kaur C Rathnasamy G Ling E-A Biology of microglia in the developing brain J Neuropathol Exp Neurol 2017 76 736 753 28859332
  33. [39]Paolicelli RC Ferretti MT Function and dysfunction of microglia during brain development: consequences for synapses and neural circuits Front Synaptic Neurosci 2017 9 9 28539882 PMC5423952
  34. [40]Hatanaka Y Wada K Kabuta T Maternal high-fat diet leads to persistent synaptic instability in mouse offspring via oxidative stress during lactation Neurochem Int 2016 97 99 108 26970392
  35. [41]Paradis J Boureau P Moyon T Nicklaus S Parnet P Paillé V Perinatal Western diet consumption leads to profound plasticity and GABAergic phenotype changes within hypothalamus and reward pathway from birth to sexual maturity in rat Front Endocrinol 2017 8 216 PMC5581815 28900415
  36. [42]Janthakhin Y Rincel M Costa A-M Darnaudéry M Ferreira G Maternal high-fat diet leads to hippocampal and amygdala dendritic remodeling in adult male offspring Psychoneuroendocrinology. 2017 83 49 57 28595087
  37. [45]Maldonado-Ruiz R Cárdenas-Tueme M Montalvo-Martínez L Vidaltamayo R Garza-Ocañas L Reséndez-Perez D Priming of hypothalamic ghrelin signaling and microglia activation exacerbate feeding in rats’ offspring following maternal overnutrition Nutrients. 2019 11 1241 PMC6627862 31159189
  38. [46]Yoon T Okada J Jung MW Kim JJ Prefrontal cortex and hippocampus subserve different components of working memory in rats Learn Mem 2008 15 97 105 18285468 PMC2275661
  39. [47]Lee A-R Kim J-H Cho E Kim M Park M Dorsal and ventral hippocampus differentiate in functional pathways and differentially associate with neurological disease-related genes during postnatal development Front Mol Neurosci 2017 10 331 29085281 PMC5650623
  40. [48]McHugh SB Campbell TG Taylor AM Rawlins JNP Bannerman DM A role for dorsal and ventral hippocampus in inter-temporal choice cost-benefit decision making Behav Neurosci 2008 122 1 8 18298243 PMC2671844
  41. [49]Spear LP The adolescent brain and age-related behavioral manifestations Neurosci Biobehav Rev 2000 24 417 463 10817843
  42. [50]Utsuyama M Hirokawa K Differential expression of various cytokine receptors in the brain after stimulation with LPS in young and old mice Exp Gerontol 2002 37 411 420 11772528
  43. [51]Skelly DT Hennessy E Dansereau M-A Cunningham C A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1Β, TNF-α and IL-6 challenges in C57BL/6 mice PLoS One 2013 8 e69123 23840908 PMC3698075
  44. [52]Gálvez-Peralta M Wang Z Bao S Knoell DL Nebert DW Tissue-specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to, inflammatory signals: Int J Toxicol. SAGE PublicationsSage CA: Los Angeles CA 2014 33 246 258 PMC4193950 24728862
  45. [53]Everhardt Queen A Moerdyk-Schauwecker M McKee LM Leamy LJ Huet YM Differential expression of inflammatory cytokines and stress genes in male and female mice in response to a lipopolysaccharide challenge PLoS One 2016 11 e0152289 27120355 PMC4847773
  46. [54]Hui CW St-Pierre A El Hajj H Remy Y Hébert SS Luheshi GN Prenatal immune challenge in mice leads to partly sex-dependent behavioral, microglial, and molecular abnormalities associated with schizophrenia Front Mol Neurosci 2018 11 13 29472840 PMC5809492
  47. [55]Bennett ML Bennett FC Liddelow SA Ajami B Zamanian JL Fernhoff NB New tools for studying microglia in the mouse and human CNS Proc Natl Acad Sci U S A 2016 113 E1738 E1746 26884166 PMC4812770
  48. [57]Paxinos G Franklin KBJ Paxinos and Franklin’s the mouse brain in stereotaxic coordinates 2013 4 Amsterdam Elsevier/Academic Press
  49. [59]Young K, Morrison H. Quantifying microglia morphology from photomicrographs of immunohistochemistry prepared tissue using ImageJ. J Vis Exp. 2018. 10.3791/57648. PMC6103256 29939190 · DOI
  50. [60]St-Pierre M-K Bordeleau M Tremblay M-È Visualizing dark microglia. Microglia 2019 New York, NY Humana 97 110 31392680
  51. [62]Chavez-Valdez R Flock DL Martin LJ Northington FJ Endoplasmic reticulum pathology and stress response in neurons precede programmed necrosis after neonatal hypoxia-ischemia Int J Dev Neurosci Off J Int Soc Dev Neurosci 2016 48 58 PMC4718855 26643212
  52. [63]De Duve C The lysosome Sci Am 1963 208 64 72 14025755
  53. [64]Holtzman E Novikoff AB Villaverde H Lysosomes and Gerl in normal and chromatolytic of the rat ganglion nodosum J Cell Biol 1967 33 419 435 4292314 PMC2108357
  54. [65]Nandy K Properties of neuronal lipofuscin pigment in mice Acta Neuropathol (Berl) 1971 19 25 32 4107379
  55. [66]Peters A, Palay SL, Webster H deF. The fine structure of the nervous system. Neurons and their Supporting Cells. 3rd edition. J Neuropathol Exp Neurol. 1991;50:282–282.
  56. [67]Maxfield FR Barbosa-Lorenzi VC Singh RK Digestive exophagy: phagocyte digestion of objects too large for phagocytosis Traffic. 2020 21 6 12 31664749 PMC7050189
  57. [68]Haka AS Barbosa-Lorenzi VC Lee HJ Falcone DJ Hudis CA Dannenberg AJ Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation J Lipid Res 2016 57 980 992 27044658 PMC4878183
  58. [70]Zhang J Reedy MC Hannun YA Obeid LM Inhibition of caspases inhibits the release of apoptotic bodies: Bcl-2 inhibits the initiation of formation of apoptotic bodies in chemotherapeutic agent-induced apoptosis J Cell Biol 1999 145 99 108 10189371 PMC2148221
  59. [72]Ohta T Toriniwa Y Ryumon N Inaba N Hirao T Yamanaka S Maternal high-fat diet promotes onset of diabetes in rat offspring Anim Sci J 2017 88 149 155 27145882
  60. [73]Hohos NM Skaznik-Wikiel ME High-fat diet and female fertility Endocrinology. 2017 158 2407 2419 28586412 PMC6283234
  61. [74]Castanon N Luheshi G Layé S Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity Front Neurosci 2015 9 229 26190966 PMC4490252
  62. [75]Kretschmer T Schulze-Edinghausen M Turnwald E-M Janoschek R Bae-Gartz I Zentis P Effect of maternal obesity in mice on IL-6 levels and placental endothelial cell homeostasis Nutrients. 2020 12 296 PMC7071123 31979004
  63. [76]Luo Y Zheng SG Hall of fame among pro-inflammatory cytokines: interleukin-6 gene and its transcriptional regulation mechanisms. Front Immunol Frontiers 2016 7 604 PMC5165036 28066415
  64. [80]Kishikawa S Sato S Kaneto S Uchino S Kohsaka S Nakamura S Allograft inflammatory factor 1 is a regulator of transcytosis in M cells Nat Commun 2017 8 1 10 28224999 PMC5322540
  65. [81]Zheng H Jia L Liu C-C Rong Z Zhong L Yang L TREM2 promotes microglial survival by activating Wnt/β-catenin pathway J Neurosci 2017 37 1772 1784 28077724 PMC5320608
  66. [82]Filipello F Morini R Corradini I Zerbi V Canzi A Michalski B The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity Immunity 2018 48 979 991.e8 29752066
  67. [83]Zhan Y Paolicelli RC Sforazzini F Weinhard L Bolasco G Pagani F Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior Nat Neurosci 2014 17 400 406 24487234
  68. [85]Kawabori M Kacimi R Kauppinen T Calosing C Kim JY Hsieh CL Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency attenuates phagocytic activities of microglia and exacerbates ischemic damage in experimental stroke J Neurosci 2015 35 3384 3396 25716838 PMC4339351
  69. [86]Chertoff M Shrivastava K Gonzalez B Acarin L Giménez-Llort L Differential modulation of TREM2 protein during postnatal brain development in mice PLoS One 2013 8 e72083 23977213 PMC3747061
  70. [87]Thrash JC Torbett BE Carson MJ Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease Neurochem Res 2009 34 38 45 18404378 PMC2655126
  71. [88]Schaefers ATU Grafen K Teuchert-Noodt G Winter Y Synaptic remodeling in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex of mice: effects of deprived rearing and voluntary running Neural Plast 2010 2010 870573 20508828 PMC2876250
  72. [89]Barrand S Crowley TM Wood-Bradley RJ Jong KAD Armitage JA Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats PLoS One 2017 12 e0189492 29240779 PMC5730210
  73. [90]MacPherson REK Castelli LM Miotto PM Frendo-Cumbo S Milburn A Roy BD A maternal high fat diet has long-lasting effects on skeletal muscle lipid and PLIN protein content in rat offspring at young adulthood Lipids. 2015 50 205 217 25552350
  74. [91]Lanham SA Roberts C Hollingworth T Sreekumar R Elahi MM Cagampang FR Maternal high-fat diet: effects on offspring bone structure Osteoporos Int 2010 21 1703 1714 19936867
  75. [92]Chen J-R Lazarenko OP Zhao H Alund AW Shankar K Maternal obesity impairs skeletal development in adult offspring J Endocrinol 2018 239 33 47 30307152 PMC6145139
  76. [93]Cardenas-Perez RE Fuentes-Mera L de la Garza AL Torre-Villalvazo I Reyes-Castro LA Rodriguez-Rocha H Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring Nutr Metab 2018 15 38 PMC5987395 29991958
  77. [94]Dahlgren J Samuelsson A-M Jansson T Holmäng A Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation Pediatr Res 2006 60 147 151 16864694
  78. [95]Wijenayake S Rahman MF Lum CMW De Vega WC Sasaki A McGowan PO Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring J Neuroinflammation 2020 17 116 32293490 PMC7158103
  79. [97]Chantong B Kratschmar DV Nashev LG Balazs Z Odermatt A Mineralocorticoid and glucocorticoid receptors differentially regulate NF-kappaB activity and pro-inflammatory cytokine production in murine BV-2 microglial cells J Neuroinflammation 2012 9 260 23190711 PMC3526453
  80. [98]Carrillo-de Sauvage MÁ Maatouk L Arnoux I Pasco M Sanz Diez A Delahaye M Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation Cell Death Differ 2013 20 1546 1557 24013726 PMC3792430
  81. [99]van Olst L Bielefeld P Fitzsimons CP de Vries HE Schouten M Glucocorticoid-mediated modulation of morphological changes associated with aging in microglia Aging Cell 2018 17 e12790 29882317 PMC6052476
  82. [100]Villa A Gelosa P Castiglioni L Cimino M Rizzi N Pepe G Sex-specific features of microglia from adult mice Cell Rep 2018 23 3501 3511 29924994 PMC6024879
  83. [101]Taylor SE, Morganti-Kossmann C, Lifshitz J, Ziebell JM. Rod microglia: a morphological definition. PLOS ONE. Public Libr Sci; 2014;9:e97096. PMC4022629 24830807
  84. [102]Ji P Schachtschneider KM Schook LB Walker FR Johnson RW Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets Brain Behav Immun 2016 54 243 251 26872419 PMC4828316
  85. [103]del Mar Fernández-Arjona M, Grondona JM, Fernández-Llebrez P, López-Ávalos MD. Microglial morphometric parameters correlate with the expression level of IL-1β, and allow identifying different activated morphotypes. Front Cell Neurosci. 2019;13:472. PMC6824358 31708746
  86. [104]Zanier ER Fumagalli S Perego C Pischiutta F De Simoni M-G Shape descriptors of the “never resting” microglia in three different acute brain injury models in mice Intensive Care Med Exp 2015 3 7 PMC4513020 26215806
  87. [105]Tay TL Béchade C D’Andrea I St-Pierre M-K Henry MS Roumier A Microglia gone rogue: impacts on psychiatric disorders across the lifespan Front Mol Neurosci 2018 10 421 29354029 PMC5758507
  88. [106]O’Loughlin E Pakan JMP Yilmazer-Hanke D McDermott KW Acute in utero exposure to lipopolysaccharide induces inflammation in the pre- and postnatal brain and alters the glial cytoarchitecture in the developing amygdala J Neuroinflammation 2017 14 212 29096641 PMC5667487
  89. [107]Hrabetova S Cognet L Rusakov DA Nägerl UV Unveiling the extracellular space of the brain: from super-resolved microstructure to in vivo function J Neurosci Soc Neuroscience 2018 38 9355 9363 PMC6706003 30381427
  90. [108]del Zoppo Gregory J Milner Richard, Mabuchi Takuma, hung Stephanie, Wang Xiaoyun, berg Greta I., et al. microglial activation and matrix protease generation during focal cerebral ischemia Stroke 2007 38 646 651 17261708
  91. [109]Lively S Schlichter LC The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion J Neuroinflammation 2013 10 843 PMC3693964 23786632
  92. [111]Kleinberger G Brendel M Mracsko E Wefers B Groeneweg L Xiang X The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism EMBO J 2017 36 1837 1853 28559417 PMC5494459
  93. [112]Noda M Doi Y Liang J Kawanokuchi J Sonobe Y Takeuchi H Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression J Biol Chem 2011 286 2308 2319 21071446 PMC3023525
  94. [113]Jay TR von Saucken VE Muñoz B Codocedo JF Atwood BK Lamb BT TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment Glia. 2019 67 1873 1892 31265185
  95. [114]Glendining KA Jasoni CL Maternal high fat diet-induced obesity modifies histone binding and expression of oxtr in offspring hippocampus in a sex-specific manner Int J Mol Sci 2019 20 329 PMC6359595 30650536
  96. [115]Mori S Leblond CP Electron microscopic features and proliferation of astrocytes in the corpus callosum of the rat J Comp Neurol 1969 137 197 225 5821844
  97. [116]Castejón OJ Astrocyte subtypes in the gray matter of injured human cerebral cortex: a transmission electron microscope study Brain Inj 1999 13 291 304 10230530
  98. [117]Schönthal AH Endoplasmic reticulum stress: its role in disease and novel prospects for therapy Scientifica. 2012 2012 857516 24278747 PMC3820435
  99. [118]Grant CW Moran-Paul CM Duclos SK Guberski DL Arreaza-Rubín G Spain LM Testing agents for prevention or reversal of type 1 diabetes in rodents PLoS One 2013 8 e72989 24023664 PMC3758263

Cited by

Sorted by citations

Authors
Bordeleau, M., Lacabanne, C., Fernández de Cossío, L., Vernoux, N., Savage, J. C., González-Ibáñez, F., & Tremblay, M.-È.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • McGill University (CA)
  • Centre de recherche du CHU de Québec-Université Laval (CA)
  • Université Laval (CA)
  • University of British Columbia (CA)
Corresponding author
Tremblay, Marie-Ève
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2020-09-05
Volume
17
Issue
1
Pages
264-264
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-020-01914-1
PMC
PMC7487673
OpenAlex
W3083252442
Cited by
85
References
19
Citations by year
2026: 6 · 2025: 16 · 2024: 19 · 2023: 10 · 2022: 23 · 2021: 10 · 2020: 1
FWCI
4.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • cIRcle (University of British Columbia) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-05308)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
maternal high-fat diet, maternal immune activation, microglia, sexual dimorphism, adolescent offspring, hippocampus, microglial morphology, astrocyte-microglia interaction, extracellular space, lipopolysaccharide response, interleukin-6, TGF-β1, TREM2, CX3CR1, TMEM119, neurodevelopmental outcomes
MeSH terms
CX3C Chemokine Receptor 1, Adolescent, Animals, Female, Hippocampus, Humans, Inflammation, Lipopolysaccharides, Male, Membrane Glycoproteins, Membrane Proteins, Neurons, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Immunologic, Sex Factors, Interleukin-6, Microglia, Maternal Nutritional Physiological Phenomena, Cell Shape, Mice, Transforming Growth Factor beta1, Diet, High-Fat

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review