Borniger JC*, Walker II WH*, Emmer KM, Zhang N, Zalenski AA, Muscarella SL, Fitzgerald JA, Smith AN, Braam CJ, TinKai T, Magalang UJ, Nelson RJ, DeVries AC. (2018). A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. Cell Metabolism. 28: 118-129. (*Co-first authors)
Here, we demonstrate that tumors in the periphery (i.e., breast cancer) deregulate satiety hormone signaling (leptin, ghrelin), leading to enhanced activity of hypocretin/orexin (HO) neurons in the lateral hypothalamus. This is associated with peripheral inflammation, sleep disruption, and changes in hepatic gluconeogenesis. Attenuation of HO neural activity rescued impairments in glucose metabolism and sleep via the sympathetic nervous system.
Borniger JC, Don RF*, Zhang N, Boyd RT, Nelson RJ. (2017) Enduring effects of perinatal nicotine exposure on murine sleep in adulthood. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 313: R280-289 (*indicates undergraduate trainee; featured article; see Frontiers for Young Minds article in Outreach)
We describe long-lasting effects of early-life nicotine exposure on sleep in adulthood. Mice that had been exposed to nicotine during gestation and prior to weaning showed marked sleep disruption in adulthood (>9 weeks after last nicotine administration). Additionally, these mice had aberrant responses to sleep deprivation, and blunted EEG delta frequencies following peripheral immune challenge.
Borniger JC, Walker WH II, Gaudier-Diaz MM, Stegman CJ*, Zhang N, Hollyfield JL, Nelson RJ, DeVries AC. (2017). Time-of-day dictates transcriptional inflammatory responses to cytotoxic chemotherapy. Scientific Reports 7: 41220 doi: 10.1038/srep41220 (*indicates undergraduate trainee) (see media coverage)
The spleen and brain demonstrate reciprocal immune responses to cytotoxic chemotherapy depending on the time-of-day it is administered. This is associated with different effects on body mass loss after treatment, and changes in the transcription of enzymes responsible for breaking down these toxic drugs in the liver.
Banner image: Drd1-Cre/Ai14 mouse hippocampal dentate gyrus
All rights reserved: Jeremy Borniger, PhD