title: Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation.
abstract: Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term electroencephalogram (EEG) biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video/EEG/electromyogram (EMG) analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24-h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was performed blind to treatment group, on each 10s EEG epoch using synchronous video, EMG and EEG trace signatures to generate individual hypnograms. Automated EEG power spectrums were analyzed for delta and theta-beta power ratios during wake vs. sleep cycles. Both control and LPS hypnograms showed an ultradian wake/sleep cycling. Since rodents are nocturnal animals, control mice showed the expected diurnal variation with significantly longer time spent in wake states during the dark cycle phase. In contrast, the LPS-treated mice lost this circadian rhythm. Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average non-rapid eye movement (NREM) cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity-dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian cycle and activity state dependent.
authors: Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: D A
authors: DA
authors: Adler
authors: Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: S
authors: S
authors: Ammanuel
authors: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: J
authors: J
authors: Lei
authors: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: T
authors: T
authors: Dada
authors: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: T
authors: T
authors: Borbiev
authors: Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: M V
authors: MV
authors: Johnston
authors: Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: kadam@kennedykrieger.org.
authors: S D
authors: SD
authors: Kadam
authors: Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA; Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: iburd1@jhmi.edu.
authors: I
authors: I
authors: Burd
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012890:Sleep / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides
keywords: EMG – electromyogram; LPS – lipopolysaccharide; TBR – theta–beta ratio; circadian; prenatal maternal infection; qEEG – quantitative electroencephalogram