title: Perinatal intermittent hypoxia alters γ-aminobutyric acid: a receptor levels in rat cerebellum.
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 GABA(A) 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 GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) 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 GABA(A) 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, GABA(A) 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 GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits.
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA. epae@dentistry.ucla.edu
authors.forename: Eung-Kwon
authors.initials: EK
authors.lastname: Pae
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Yoon
authors.forename: Bhoomika
authors.initials: B
authors.lastname: Ahuja
authors.forename: Gary W
authors.initials: GW
authors.lastname: Lau
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Nguyen
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Harper
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D053938:DNA Fragmentation; D005260:Female; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D020033:Protein Isoforms / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid