Prenatal Activation of Glucocorticoid Receptors Induces Memory Impairment in a Sex-Dependent Manner: Role of Cyclooxygenase-2

Autor: Mai Abul, Maie Dawoud Al-Bader, Abdeslam Mouihate
Rok vydání: 2022
Předmět:
Zdroj: Molecular Neurobiology. 59:3767-3777
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-022-02820-8
Popis: Prenatal exposure to dexamethasone (DEX) results in long-lasting effects on cognitive functions such as learning and memory impairment. However, the mechanisms underlying these DEX-induced deleterious effects are not well known. Here, we assessed whether cyclooxygenase-2 (COX-2) is involved in the impact of prenatal exposure to DEX on learning and memory during adulthood. Pregnant Sprague-Dawley rats received daily injections of either DEX (0.2 mg/kg; i.p.) or saline from gestation day (GD) 14 until GD21. Gene and protein expression of COX-2, as well as presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein-95) proteins, were monitored in the dorsal and ventral hippocampi of adult male and female offspring. A different cohort of adult male and female rat offspring was given daily injections of either vehicle or a specific COX-2 inhibitor (celecoxib 10 mg/kg, i.p.) for 5 consecutive days and was subsequently subjected to Morris water maze memory test. Prenatal DEX enhanced the expression of COX-2 protein and cox-2 mRNA in the dorsal hippocampus of adult female but not male rats. This enhanced COX-2 expression was associated with reduced expression in pre- and postsynaptic proteins and altered memory acquisition and retention. Administration of COX-2-specific inhibitor alleviated prenatal DEX-induced memory impairment in adult female rats. This study suggests that prenatal activation of glucocorticoid receptors stimulates COX-2 gene and protein expression and impairs hippocampal-dependent spatial memory in female but not male rat offspring. Furthermore, COX-2 selective inhibitors can be used to alleviate the long-lasting deleterious effects of corticosteroid medication during pregnancy.
Databáze: OpenAIRE
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