Journal Articles

Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915

Browse

Filters

2019 - 201912020 - 20253

Settings

Subject: search.filters.subject.brain

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    N-terminal oligomerization drives HDAC4 nuclear condensation and neurodevelopmental dysfunction in Drosophila
    (The Royal Society, 2025-10) Hawley HR; Sutherland-Smith AJ; Savoian MS; Fitzsimons HL
    Histone deacetylase four (HDAC4) undergoes dynamic nucleocytoplasmic shuttling, a process critical for regulating its activity. However, aberrant nuclear accumulation of HDAC4 is associated with both neurodevelopmental and neurodegenerative disease, and in our Drosophila model, impairs normal neuronal development. Upon nuclear accumulation, HDAC4 forms biomolecular condensates, previously termed aggregates, that correlate with the severity of defects in development of the Drosophila mushroom body and adult eye. Here we determined that nuclear condensation of HDAC4 is dependent on self-oligomerization, and that impairing oligomerization reduces condensation and the severity of neurodevelopmental phenotypes in Drosophila. HDAC4 condensates are highly dynamic and are stabilized by the presence of MEF2, which promotes their formation, ultimately exacerbating phenotypic severity. These data provide insight into the role of HDAC4 condensates in normal neuronal function and suggest that their dysregulation may contribute to neurodevelopmental disorders. Consequently, targeting oligomerization of HDAC4 and its interaction with MEF2 present potential therapeutic strategies for diseases associated with HDAC4 nuclear accumulation.
  • Thumbnail Image
    Item
    Gut-Brain Axis in the Early Postnatal Years of Life: A Developmental Perspective
    (Frontiers Media S.A., 2020-08-05) Jena A; Montoya CA; Mullaney JA; Dilger RN; Young W; McNabb WC; Roy NC; Cammarota M
    Emerging evidence suggests that alterations in the development of the gastrointestinal (GI) tract during the early postnatal period can influence brain development and vice-versa. It is increasingly recognized that communication between the GI tract and brain is mainly driven by neural, endocrine, immune, and metabolic mediators, collectively called the gut-brain axis (GBA). Changes in the GBA mediators occur in response to the developmental changes in the body during this period. This review provides an overview of major developmental events in the GI tract and brain in the early postnatal period and their parallel developmental trajectories under physiological conditions. Current knowledge of GBA mediators in context to brain function and behavioral outcomes and their synthesis and metabolism (site, timing, etc.) is discussed. This review also presents hypotheses on the role of the GBA mediators in response to the parallel development of the GI tract and brain in infants.
  • Thumbnail Image
    Item
    Lipidomics of Brain Tissues in Rats Fed Human Milk from Chinese Mothers or Commercial Infant Formula
    (MDPI (Basel, Switzerland), 2019-10-28) Su M; Subbaraj AK; Fraser K; Qi X; Jia H; Chen W; Gomes Reis M; Agnew M; Day L; Roy NC; Young W
    Holistic benefits of human milk to infants, particularly brain development and cognitive behavior, have stipulated that infant formula be tailored in composition like human milk. However, the composition of human milk, especially lipids, and their effects on brain development is complex and not fully elucidated. We evaluated brain lipidome profiles in weanling rats fed human milk or infant formula using non-targeted UHPLC-MS techniques. We also compared the lipid composition of human milk and infant formula using conventional GC-FID and HPLC-ELSD techniques. The sphingomyelin class of lipids was significantly higher in brains of rats fed human milk. Lipid species mainly comprising saturated or mono-unsaturated C18 fatty acids contributed significantly higher percentages to their respective classes in human milk compared to infant formula fed samples. In contrast, PUFAs contributed significantly higher percentages in brains of formula fed samples. Differences between human milk and formula lipids included minor fatty acids such as C8:0 and C12:0, which were higher in formula, and C16:1 and C18:1 n11, which were higher in human milk. Formula also contained higher levels of low- to medium-carbon triacylglycerols, whereas human milk had higher levels of high-carbon triacylglycerols. All phospholipid classes, and ceramides, were higher in formula. We show that brain lipid composition differs in weanling rats fed human milk or infant formula, but dietary lipid compositions do not necessarily manifest in the brain lipidome.
  • Thumbnail Image
    Item
    Infant nutrition affects the microbiota-gut-brain axis: Comparison of human milk vs. infant formula feeding in the piglet model
    (MDPI (Basel, Switzerland ), 2022-09-21) Charton E; Bourgeois A; Bellanger A; Le-Gouar Y; Dahirel P; Romé V; Randuineau G; Cahu A; Moughan PJ; Montoya CA; Blat S; Dupont D; Deglaire A; Le Huërou-Luron I; Benítez-Páez A
    Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow’s milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.