Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques

• Published in: Journal of neurophysiology Vol. 131; no. 2; pp. 241 - 260
• Main Authors: Papadakis, Samantha, Thompson, Jacqueline R, Feczko, Eric, Miranda-Dominguez, Oscar, Dunn, Geoffrey A, Selby, Matthew, Mitchell, A J, Sullivan, Elinor L, Fair, Damien A
• Format: Journal Article
• Language: English
• Published: United States 01.02.2024
• Subjects: Animals; Arcuate Nucleus of Hypothalamus; Diet, High-Fat - adverse effects; Female; Follow-Up Studies; Hypothalamus; Macaca; Macaca fuscata; Microglia; Neuroinflammatory Diseases; Pregnancy; high-fat high-sugar Western-style diet; arcuate nucleus of the hypothalamus; nonhuman primates; neuroinflammation; microglia
• ISSN: 0022-3077; 1522-1598; 1522-1598
• DOI: 10.1152/jn.00213.2023

Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet ( = 0.011) and spatial location ( = 0.003) on Iba1-stained cell count. Perinatal WSD exposure was associated with a slight decrease in the number of Iba1-stained cells, and cells were more densely located in the center of the ARC. These findings suggest that the heightened inflammatory state experienced in utero does not persist postnatally. This inflammatory response trajectory could have important implications for understanding how neurodevelopmental disorders progress. Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.