التفاصيل البيبلوغرافية
| العنوان: |
Early life high fructose exposure disrupts microglia function and impedes neurodevelopment. |
| المؤلفون: |
Wang Z, Lipshutz A, Liu ZL, Trzeciak AJ, Miranda IC, Martínez de la Torre C, Schild T, Lazarov T, Rojas WS, Saavedra PHV, Romero-Pichardo JE, Baako A, Geissmann F, Faraco G, Gan L, Etchegaray JI, Lucas CD, Parkhurst CN, Zeng MY, Keshari KR, Perry JSA |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 15. Date of Electronic Publication: 2023 Aug 15. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Despite the success of fructose as a low-cost food additive, recent epidemiological evidence suggests that high fructose consumption by pregnant mothers or during adolescence is associated with disrupted neurodevelopment 1-7 . An essential step in appropriate mammalian neurodevelopment is the synaptic pruning and elimination of newly-formed neurons by microglia, the central nervous system's (CNS) resident professional phagocyte 8-10 . Whether early life high fructose consumption affects microglia function and if this directly impacts neurodevelopment remains unknown. Here, we show that both offspring born to dams fed a high fructose diet and neonates exposed to high fructose exhibit decreased microglial density, increased uncleared apoptotic cells, and decreased synaptic pruning in vivo . Importantly, deletion of the high affinity fructose transporter SLC2A5 (GLUT5) in neonates completely reversed microglia dysfunction, suggesting that high fructose directly affects neonatal development. Mechanistically, we found that high fructose treatment of both mouse and human microglia suppresses synaptic pruning and phagocytosis capacity which is fully reversed in GLUT5-deficient microglia. Using a combination of in vivo and in vitro nuclear magnetic resonance- and mass spectrometry-based fructose tracing, we found that high fructose drives significant GLUT5-dependent fructose uptake and catabolism, rewiring microglia metabolism towards a hypo-phagocytic state. Importantly, mice exposed to high fructose as neonates exhibited cognitive defects and developed anxiety-like behavior which were rescued in GLUT5-deficient animals. Our findings provide a mechanistic explanation for the epidemiological observation that early life high fructose exposure is associated with increased prevalence of adolescent anxiety disorders. |
| معلومات مُعتمدة: |
K08 MH130773 United States MH NIMH NIH HHS; T32 CA254875 United States CA NCI NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230830 Latest Revision: 20240607 |
| رمز التحديث: |
20240607 |
| مُعرف محوري في PubMed: |
PMC10462086 |
| DOI: |
10.1101/2023.08.14.553242 |
| PMID: |
37645894 |
| قاعدة البيانات: |
MEDLINE |
