Progesterone’s effects to reduce anxiety behavior of aged mice do not require actions via intracellular progestin receptors

Frye, Cheryl A.; Sumida, Kanako; Dudek, Bruce C.; Harney, Jacob P.; Lydon, John P.; O’Malley, Bert W.; Pfaff, Donald W.; Rhodes, Madeline E.

doi:10.1007/s00213-006-0309-3

Cited by 63 publications

(76 citation statements)

References 65 publications

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“…Behavioral testing commenced following a 5-day handling procedure that was utilized to habituate mice to handling and behavioral observation by the experimenter (modified as per Frye et al 2006b). On day 1, mice were picked up from their homecage, handled for 15 s, and returned to their homecage.…”

Section: Handling Proceduresmentioning

confidence: 99%

“…The maze is circular (40 cm in diameter with 5 cm wide runways) and elevated 70 cm above the ground. The total time spent in the closed and open quadrants was recorded for 5 min (as per Frye et al 2006b). The total duration of time spent in the open quadrants is considered to reflect reduced anxiety-like behavior.…”

Section: Elevated Zero Mazementioning

confidence: 99%

“…Motor coordination of mice was assessed using the Accurotor Roto-Rod Apparatus (AccuScan Instruments, Columbus, OH; Frye et al 2006b). In this task, the rods were 3 cm in diameter and elevated 35 cm above the floor.…”

Section: Rotarodmentioning

confidence: 99%

“…Mice were first habituated to this task with three 30 s trials. One hour later, mice were tested with the rod rotating at constant speed of 20 rpm (Frye et al 2006b). Mice had two trials in this testing session and the latency to fall from the rod was recorded (maximum latency = 180 s).…”

Section: Rotarodmentioning

confidence: 99%

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Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Frye

Walf

2009

AGE

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Although anxiety and depression are not the core symptoms of Alzheimer's Disease (AD), there are changes observed in mood in those with AD, as well as in the aging population. Anxiety and depression may be influenced by progesterone P 4 and/or its neuroactive metabolites, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP). To begin to investigate progestogens' role in AD, a double transgenic mouse model of early-onset familial AD that cooverexpresses mutant forms of amyloid precursor protein (APPswe) and presenilin 1 Δ exon 9 mutation was utilized. As such, the effects of long-term (from 6 to 12 months of age) administration of P 4 to ovariectomized (ovx) wildtype and APPswe+PSEN1Δe9 mice for changes in affective behavior was investigated. APPswe+PSEN1Δ9 mutant mice had increased anxiety-like (i.e., increased emergence latencies, decreased time spent on the open quadrants of the elevated zero maze) and increased depressive-like behavior (i.e., increased time spent immobile) than did wildtype mice. Compared to vehicle-administration, P 4 administration (which produced physiological circulating P 4 , DHP, and 3α,5α-THP levels, particularly in the wildtype mice) decreased depressant-like behavior in the forced swim test. These effects occurred independent of changes in general motor behavior/coordination, pain threshold, and plasma corticosterone levels. Thus, the APPswe+PSEN1Δ9 mutation alters affective behavior, and P 4 treatment reversed depressive-like behavior.

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Section: Handling Proceduresmentioning

confidence: 99%

Section: Elevated Zero Mazementioning

confidence: 99%

Section: Rotarodmentioning

confidence: 99%

Section: Rotarodmentioning

confidence: 99%

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Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Frye

Walf

2009

AGE

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show abstract

“…The following procedure was utilized to habituate mice to handling and behavioral observation by the experimenter before behavioral testing began (Frye et al, 2006a). On day 1, mice were picked up from their home cage, handled for 15 s, and returned to their home cage.…”

Section: Handling Proceduresmentioning

confidence: 99%

Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks

Frye

Walf

2008

Neurobiology of Learning and Memory

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Research on how steroid hormones mediate mnemonic processes have focused on effects of 17β-estradiol (E 2 ); yet, progesterone (P 4 ) co-varies with E 2 across endogenous hormonal milieu, and itself may influence cognitive processes. We investigated the hypothesis that acute P 4 treatment enhances cognitive performance compared to vehicle. Ovariectomized (OVX) c57/BL6J mice were randomly assigned to be subcutaneously injected with oil vehicle or P 4 (10 mg/kg). Mice were trained in the spontaneous alternation, object recognition, object placement, water maze, or fear conditioning tasks, and injected with vehicle or P 4 before training or immediately post-training, and then were tested 1, 4, or 24 h later. The data obtained from these experiments supported our hypothesis. P 4 increased the percentage of spontaneous alterations made in a T-maze more so than did vehicle. P 4 , compared to vehicle, increased the percentage of time spent exploring the novel object in the object recognition task, but did not alter performance in the object placement task. P 4 , compared to vehicle, decreased latencies to reach the location in the water maze where the platform had been during training in a probe trial, but did not alter performance in the control, cued trial. Compared to vehicle, P 4 treatment increased freezing in contextual and cued fear testing. Thus, acute P 4 treatment to OVX mice can improve cognitive performance across a variety of tasks.

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Menstrual cycle‐driven hormone concentrations co‐fluctuate with white and gray matter architecture changes across the whole brain

Rizor,

Babenko,

Dundon

et al. 2024

Human Brain Mapping

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Cyclic fluctuations in hypothalamic–pituitary–gonadal axis (HPG‐axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1‐weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid‐luteal) to investigate whether HPG‐axis hormone concentrations co‐fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β‐estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β‐estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle‐stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = −0.749, HDI = [−11.604, −0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain‐wide changes in human WM microstructure and CT coinciding with menstrual cycle‐driven hormone rhythms. Effects were observed in both classically known HPG‐axis receptor‐dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG‐axis hormone fluctuations may have significant structural impacts across the entire brain.

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Progesterone’s effects to reduce anxiety behavior of aged mice do not require actions via intracellular progestin receptors

Abstract: The effects of P to decrease anxiety behavior of younger and older mice do not require classic PRs and may involve actions of 3alpha,5alpha-THP at GBRs.

Cited by 63 publications

References 65 publications

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks

Menstrual cycle‐driven hormone concentrations co‐fluctuate with white and gray matter architecture changes across the whole brain

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