Progesterone (P) is an endogenous anticonvulsant hormone. P is being evaluated as a treatment for epilepsy, traumatic brain injury, and other complex neurological conditions. Preclinical and clinical studies suggest that P appears to interrupt epileptogenic events. However, the potential disease-modifying effect of P in epileptogenic models is not widely investigated. In this study, we examined the effects of P on the development of hippocampus kindling in female mice. In addition, we determined the role of progesterone receptors (PR) in the P's effect on the kindling epileptogenesis utilizing PR knockout (PRKO) mice. P, at 25 mg/kg, did not affect seizures and did not exert sedative/motor effects in fully-kindled mice. P treatment (25 mg/kg, twice daily for 2 weeks) significantly suppressed the rate of development of behavioral kindled seizure activity evoked by daily hippocampus stimulation in wild-type (WT) mice, indicating a disease-modifying effect of P on limbic epileptogenesis. There was a significant increase in the rate of 'rebound or withdrawal' kindling during drug-free stimulation sessions following abrupt discontinuation of P treatment. A washout period after termination of P treatment prevented such acceleration in kindling. PRKO mice were kindled significantly slower than WT mice, indicating a modulatory role of PRs in seizure susceptibility. P's effects on early kindling progression was partially decreased in PRKO mice, but the overall (˜2-fold) delay in the rate of kindling for the induction of stage 5 seizures was unchanged in PRKO mice. Moreover, the acute anticonvulsant effect of P was undiminished in fully-kindled PRKO mice. These studies suggest that P exerts disease-modifying effects in the hippocampus kindling model at doses that do not significantly affect seizure expression and motor performance, and the kindling-retarding effects of P may occur partly through a complex PR-dependent and PR-independent mechanism.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963708 | PMC |
| http://dx.doi.org/10.1016/j.neuropharm.2010.08.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to pain during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone.
View Article and Find Full Text PDFLimbic progesterone receptors regulate spatial memory.
Sci Rep
February 2023
Department of Neurology, University of Virginia, Health Sciences Center, P.O. Box 801330, Charlottesville, VA, 22908, USA.
Progesterone and its receptors (PRs) participate in mating and reproduction, but their role in spatial declarative memory is not understood. Male mice expressed PRs, predominately in excitatory neurons, in brain regions that support spatial memory, such as the hippocampus and entorhinal cortex (EC). Furthermore, segesterone, a specific PR agonist, activates neurons in both the EC and hippocampus.
View Article and Find Full Text PDFIntraovarian, Isoform-Specific Transcriptional Roles of Progesterone Receptor in Ovulation.
Cells
May 2022
Robinson Research Institute, School of Biomedicine, University of Adelaide, Adelaide 5000, Australia.
Progesterone receptor (PGR) activity is obligatory for mammalian ovulation; however, there is no established direct functional pathway explaining how progesterone receptor completely and specifically regulates oocyte release. This study examined the overarching cell- and isoform-specific effects of the PGR within each cellular compartment of the ovary, using mice null for the PGR (PRKO), as well as isoform-specific null mice. The PGR was expressed in ovarian granulosa and stromal cells and although PRKO ovaries showed no visible histological changes in preovulatory ovarian morphology, follicle rupture did not occur.
View Article and Find Full Text PDFProgesterone's Effects on Cognitive Performance of Male Mice Are Independent of Progestin Receptors but Relate to Increases in GABA Activity in the Hippocampus and Cortex.
Front Endocrinol (Lausanne)
May 2021
Department of Psychology, The University at Albany-SUNY, Life Sciences, Albany, NY, United States.
Progestogens' (e.g., progesterone and its neuroactive metabolite, allopregnanolone), cognitive effects and mechanisms among males are not well-understood.
View Article and Find Full Text PDFDevelopmental expression of genes involved in progesterone synthesis, metabolism and action during the post-natal cerebellar myelination.
J Steroid Biochem Mol Biol
March 2021
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Obligado 2490, 1428 Buenos Aires, Argentina; Department of Human Biochemistry, University of Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina. Electronic address:
Progesterone is involved in dendritogenesis, synaptogenesis and maturation of cerebellar Purkinge cells, major sites of steroid synthesis in the brain. To study a possible time-relationship between myelination, neurosteroidogenesis and steroid receptors during development of the postnatal mouse cerebellum, we determined at postnatal days 5 (P5),18 (P18) and 35 (P35) the expression of myelin basic protein (MBP), components of the steroidogenic pathway, levels of endogenous steroids and progesterone's classical and non-classical receptors. In parallel with myelin increased expression during development, P18 and P35 mice showed higher levels of cerebellar progesterone and its reduced derivatives, higher expression of steroidogenic acute regulatory protein (StAR) mRNA, cholesterol side chain cleavage enzyme (P450scc) and 5α-reductase mRNA vs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!