Perinatal intermittent hypoxia alters γ‐aminobutyric acid: a receptor levels in rat cerebellum

International Journal of Developmental Neuroscience - Tập 29 - Trang 819-826 - 2011
Eung-Kwon Pae1, Audrey J. Yoon1, Bhoomika Ahuja1, Gary W. Lau1, Daniel D. Nguyen1, Yong Kim1, Ronald M. Harper2
1UCLA School of Dentistry, United States
2UCLA Neurobiology, United States

Tóm tắt

Abstract

Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ‐aminobutyric (GABA)‐A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABAA receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABAA receptor profiles following 5‐h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240 s) or room‐air control in groups of male and female rat pups on postnatal d 1–2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABAA receptors α6, normalized to a house‐keeping gene GAPDH, and assessed using real‐time reverse‐transcriptase PCR assays were up‐regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time‐course. In contrast, GABAA α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post‐transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH‐exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down‐regulation of GABAA receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits.


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