Transient neonatal sleep fragmentation results in long-term neuroinflammation and cognitive impairment in a rabbit model

Sarah J. Bertrand, Zhi Zhang, Ruchit Patel, Caroline O'Ferrell, Naresh M. Punjabi, Sapna R. Kudchadkar, Sujatha Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2–3 weeks post-fragmentation and were sacrificed 3–50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

Original languageEnglish (US)
Article number113212
JournalExperimental Neurology
Volume327
DOIs
StatePublished - May 2020

Keywords

  • Cognition
  • Cytokines
  • Inflammation
  • Microglia
  • Neonates
  • Rabbit
  • Sleep fragmentation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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