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• W2022243072 abstract "In female rodents, sleep and activity levels fluctuate over the estrous cycle. When estradiol (E 2 ) levels are highest, sleep is reduced whereas locomotion is increased. The preoptic area (POA) is a key site for estrogenic regulation of these functions. However, molecular mechanisms by which E 2 acts to reduce sleep and increase activity are unclear. Recently, we demonstrated a twofold reduction in lipocalin-type prostaglandin D synthase (L-PGDS) transcript levels, after E 2 treatment, in the ventrolateral POA (VLPO), a putative sleep-active nucleus. Catalytic activity of L-PGDS produces PGD 2 , an endogenous somnogen. Thus, we hypothesized that decreases in PGD 2 in the VLPO may contribute to the generalized arousal mediated by estrogens. To test this, we infused ( i ) antisense oligonucleotides (oligos), containing locked nucleic acid moieties (an improved technology), targeted to L-PGDS mRNA, ( ii ) scrambled sequence control oligos, or ( iii ) saline vehicle into the VLPO of ovariectomized female mice treated with E 2 or oil. Arousal states and activity levels were assessed in response to a series of sensory stimuli (vestibular, olfactory, and somatosensory). The vestibular stimulus, which was administered first, resulted in the strongest responses and elicited significantly different responses among the groups: all groups in the E 2 cohort demonstrated increases in overall home cage activity and duration of that activity compared with the oil-treated control groups. As predicted from E 2 suppression of L-PGDS transcript levels, the responses of the locked nucleic acid antisense oligo-treated animals from the oil cohort did not differ from the E 2 -treated groups, such that they also demonstrated increases in activity and duration of activity compared with their controls. Thus, reducing L-PGDS in the VLPO of oil-treated females mimicked the effect of E 2 on activity and arousal and represents a unique molecular pathway through which E 2 may modulate these functions." @default.
• W2022243072 created "2016-06-24" @default.
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• W2022243072 date "2003-11-24" @default.
• W2022243072 modified "2023-10-16" @default.
• W2022243072 title "Reduction of lipocalin-type prostaglandin D synthase in the preoptic area of female mice mimics estradiol effects on arousal and sex behavior" @default.
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• W2022243072 doi "https://doi.org/10.1073/pnas.2436540100" @default.
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