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.

Urinary Neurotransmitters Are Selectively Altered in Children With Obstructive Sleep Apnea and Predict Cognitive Morbidity

“…Indeed, animal studies suggest that the presence of intermittent hypoxia is associated with signifi cant alterations in GABAergic neurotransmission. [26][27][28] Similarly, taurine is known to play important roles against reactive oxygen species and hypoxia in several organs, including the those of the CNS and the vasculature. [29][30][31][32][33] Both intermittent hypoxia and increased oxidative stress are hallmark characteristics of OSA, 34 and the degree of oxidative stress associated with OSA has emerged as an important determinant of cognitive dysfunction in both animal models and in children.…”

Transient Intermittent Hypoxia Exposure Disrupts Neonatal Bone Strength

“…Near end-term pregnant Sprague-Dawley rats were purchased and maintained until parturition. Within 3 h after birth, 12 offspring (5 males and 7 females), together with the mother of this experimental group, were randomly placed in a customized IH chamber that alternated oxygen concentration between room air (20.5% O 2 ) and a hypoxic condition (12% O 2 ) every 240 s for 1 h, with food and water accessible ad libitum , as described previously ( 9 , 21 ). Ten control pups (five males and five females) and their mother were maintained in room air.…”

Insulin Production Hampered by Intermittent Hypoxia via Impaired Zinc Homeostasis

“…On the first day of birth, dams along with their pups were randomly selected and designated the control and IH groups. The animals were housed in commercially designed chambers with food and water accessible ad libitum , as previously described [18]. The experimental group was maintained at oxygen concentrations that alternated between room air, 20.5% and 10% every 240s for 1 h; and the control animals were maintained in room air oxygen concentration for 1h.…”