Intermittent hypoxic exposure during light phase induces changes in cAMP response element binding protein activity in the rat CA1 hippocampal region: water maze performance correlates
Section snippets
Experimental procedures
Young adult Sprague–Dawley male rats (60–75 days of age; weight: 175–200 g), were purchased from Charles River Laboratories (Wilmington, MA, USA), and used for all experiments. The experimental protocols were approved by the institutional animal use and care committee, and are in close agreement with the National Institutes of Health guide for the care and use of laboratory animals. Every effort was made to minimize the number of animals used and their suffering.
IH and CREB expression in CA1 region of hippocampus
In six separate experiments, IH exposures induced marked and early decreases in pCREB compared with normoxia (Fig. 1). These reductions in pCREB occurred as early as 1 h of IH exposure (P<0.05), and reached their nadir at 6 h to 3 days (P<0.01). Subsequent recovery of pCREB expression developed, such that by 14 and 30 days IH pCREB returned to normoxic levels and beyond. In contrast, the expression of total CREB was not affected throughout the duration of IH exposure (Fig. 1).
To assess whether
Discussion
The present study shows evidence for a biphasic pattern in CREB phosphorylation occurring in the CA1 region of the rat hippocampus following IH exposures, and that the time course of these changes is highly reminiscent of changes in IH-induced neuronal apoptosis within that region. Furthermore, we show that the pattern of pCREB nuclear binding closely resembles that of the changes in spatial reference function following IH exposures, further suggesting that these phenomena may be
Acknowledgements
This study was supported by National Institutes of Health grants NIH HL-63912, HL-69932 to D.G., P20 RR-15576 to E.G., and HD-42395 to B.W.R.
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