title: Increased expression of Hes5 protein in Notch signaling pathway in the hippocampus of mice offspring of dams fed a high-fat diet during pregnancy and suckling.
abstract: Maternal high-fat diet (HFD) impairs hippocampal development of offspring promoting decreased proliferation of neural progenitors, in neuronal differentiation, in dendritic spine density and synaptic plasticity reducing neurogenic capacity. Notch signaling pathway participates in molecular mechanisms of the neurogenesis. The activation of Notch signaling leads to the upregulation of Hes5, which inhibits the proliferation and differentiation of neural progenitors. This study aimed to investigate the Notch/Hes pathway activation in the hippocampus of the offspring of dams fed an HFD. Female Swiss mice were fed a control diet (CD) and an HFD from pre-mating until suckling. The bodyweight and mass of adipose tissue in the mothers and pups were also measured. The mRNA and protein expression of Notch1, Hes5, Mash1, and Delta1 in the hippocampus was assessed by RT-PCR and western blotting, respectively. Dams fed the HFD and their pups had an increased bodyweight and amount of adipose tissue. Furthermore, the offspring of mothers fed the HFD exhibited an increased Hes5 expression in the hippocampus compared with CD offspring. In addition, HFD offspring also expressed increased amounts of Notch1 and Hes5 mRNA, whereas Mash1 expression was decreased. However, the expression of Delta1 did not change significantly. We propose that the overexpression of Hes5, a Notch effector, downregulates the expression of the proneural gene Mash1 in the offspring of obese mothers, delaying cellular differentiation. These results provide further evidence that an offspring's hippocampus is molecularly susceptible to maternal HFD and suggest that Notch1 signaling in this brain region is important for neuronal differentiation.
authors.affiliation: Laboratory of Neuroscience and Nutrition, Department of Biosciences, Federal University of Sao Paulo/UNIFESP (Campus Baixada Santista), 11060-001 Santos, SP, Brazil; Laboratory of Metabolism Disorders, Faculty of Applied Sciences, State University of Campinas (UNICAMP), 13484-350 Limeira, SP, Brazil. Electronic address: cmendes11@hotmail.com.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Mendes-da-Silva
authors.affiliation: Laboratory of Metabolism Disorders, Faculty of Applied Sciences, State University of Campinas (UNICAMP), 13484-350 Limeira, SP, Brazil.
authors.forename: Simone Ferreira
authors.initials: SF
authors.lastname: Lemes
authors.affiliation: Laboratory of Metabolism Disorders, Faculty of Applied Sciences, State University of Campinas (UNICAMP), 13484-350 Limeira, SP, Brazil.
authors.forename: Tanyara da Silva
authors.initials: Tda S
authors.lastname: Baliani
authors.affiliation: Laboratory of Metabolism Disorders, Faculty of Applied Sciences, State University of Campinas (UNICAMP), 13484-350 Limeira, SP, Brazil.
authors.forename: Milena Diorio
authors.initials: MD
authors.lastname: Versutti
authors.affiliation: Laboratory of Metabolism Disorders, Faculty of Applied Sciences, State University of Campinas (UNICAMP), 13484-350 Limeira, SP, Brazil.
authors.forename: Marcio Alberto
authors.initials: MA
authors.lastname: Torsoni
mesh_terms: D000273:Adipose Tissue; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D007774:Lactation / Q000502:physiology; D008297:Male; D033261:Maternal-Fetal Relations; D051379:Mice; D055495:Neurogenesis; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C527353:GE fusion protein, mouse; C489685:Hes5 protein, mouse
keywords: High-fat diet; Hippocampus; Lactation; Maternal obesity; Notch signaling; Pregnancy