Original contributionEpisodic neonatal hypoxia evokes executive dysfunction and regionally specific alterations in markers of dopamine signaling
Section snippets
Subject characteristics and sample size
Male and female offspring of three Harlan Sprague–Dawley rats were studied. All protocols and procedures were approved by the local Institutional Animal Care and Use Committee. A 12-h light/dark cycle (lights on at 0700 h) was maintained throughout the study, food and water were provided ad libitum unless otherwise stated. Power analyses were used to determined appropriate sample sizes necessary to achieve a minimum statistical power (0.85, α=0.05) for comparisons of sleep–wake architecture,
Statistical analyses
One experimental group (post-hypoxic rats) and two parallel control groups (normoxic rats and unhandled rats) were included in the experimental paradigm. Statistical analyses were performed using the software program SPSS, version 10.0.5 (Chicago, IL, USA). One-way analysis of variance with Bonferroni and Tukey post-hoc analyses was performed to examine differences in behavioral and neurochemical traits between post-hypoxic, normoxic, and unhandled rats. Both normoxic and unhandled rat values
Gender effects
No gender-related differences were identified in either control or post-hypoxic rats with regards to values of sleep–wake architecture, measures of locomotor activity, or RAM performance. Expression of VMAT2 and TH proteins, however, were significantly greater in the striatum of female control rats than in male control rats. These differences are described in detail in the results section of Western blot analyses.
Sleep–wake architecture
Sleep–wake architecture differed between post-hypoxic and control rats.
Discussion
The aim of this study was to determine if intermittent hypoxic insults, occurring during a period of critical brain development, would disrupt the functional integrity of the mesotelencephalic DA system and evoke behavioral and cognitive deficiencies. We demonstrate that rats exposed to intermittent hypoxic insults between PN 7 and 11, a developmental period comparable to the preterm human born between 32 and 36 weeks of gestation (Romijn et al., 1991), lead to increased sleep, locomotor
Acknowledgements
This work is supported by HL-72722 and the Department of Neurology, Emory University (M.J.D.), NS-36695 and NS-40221 (D.B.R.).
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