Novel anticonvulsive effects of progesterone in a mouse model of hippocampal electrical kindling

Jeffrey, Melanie; Lang, Min; Gane, Jonathan; Chow, Elbert; Wu, Chenggang; Zhang, L.

doi:10.1016/j.neuroscience.2013.10.074

Cited by 23 publications

(56 citation statements)

References 48 publications

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“…Indeed, to our knowledge, the effects of finasteride have so far generally been explored after the administration of very high doses [2,8,9,10,11,12,13,14,15,16,17,18]. We demonstrated that, in agreement with the well-known effect of finasteride in the prostate [35], a significant decrease in its relative weight was observed at the end of the subchronic treatment with the drug.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the metabolites of PROG and T are involved in the regulation of neuroendocrine events, behavior, affection, learning and memory, synaptic and glial plasticity and adult hippocampal neurogenesis as well as in the response of brain tissue to injury and neurodegeneration (i.e., regulating neuronal survival, axonal regeneration and gliosis) [1,5,6,7]. Finasteride has been used as a tool to evaluate whether the effects of PROG or T in the nervous tissue could be ascribed to their conversion into 5α-reduced metabolites [2,8,9,10,11,12,13,14,15,16,17,18]. However, despite of the wide therapeutic use of this inhibitor (e.g., human benign prostatic hyperplasia and androgenic alopecia), the effects of finasteride per se in the nervous system have been poorly explored.…”

Section: Introductionmentioning

confidence: 99%

“…However, despite of the wide therapeutic use of this inhibitor (e.g., human benign prostatic hyperplasia and androgenic alopecia), the effects of finasteride per se in the nervous system have been poorly explored. The effects of short exposures (i.e., a few days) to high doses (i.e., 50 mg/kg) of finasteride have been assessed in experimental models [2,8,9,10,11,12,13,14,15,16,17,18]. However, the effects of subchronic treatments with finasteride at low doses, more similar to those used in clinical practice, and the consequences of its withdrawal have yet to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

et al. 2015

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The enzymatic conversion of progesterone and testosterone by the enzyme 5alpha-reductase exerts a crucial role in the control of nervous function. The effects of finasteride in the brain, an inhibitor of this enzyme used for the treatment of human benign prostatic hyperplasia and androgenic alopecia, have been poorly explored. Therefore, the effects of a subchronic treatment with finasteride at low doses (3 mg/kg/day) and the consequences of its withdrawal on neuroactive steroid levels in plasma, cerebrospinal fluid and some brain regions as well as on the expression of classical and non-classical steroid receptors have been evaluated in male rats. After subchronic treatment (i.e., for 20 days) the following effects were detected: (i) depending on the compartment considered, alteration in the levels of neuroactive steroids, not only in 5alpha-reduced metabolites but also in its precursors and in neuroactive steroids from other steroidogenic pathways and (ii) an upregulation of the androgen receptor in the cerebral cortex and beta3 subunit of the GABA-A receptor in the cerebellum. One month after the last treatment (i.e., withdrawal period), some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex, an increase of dihydroprogesterone in the cerebellum, a decrease of dihydrotestosterone in plasma). Moreover, other changes in neuroactive steroid levels, steroid receptors (i.e., an upregulation of the estrogen receptor alpha and a downregulation of the estrogen receptor beta in the cerebral cortex) and GABA-A receptor subunits (i.e., a decrease of alpha 4 and beta 3 mRNA levels in the cerebral cortex) were detected. These findings suggest that finasteride treatment may have broad consequences for brain function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

et al. 2015

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“…Electrode implantation, EEG recordings and analysis were done as previously described (El-Hayek et al, 2011;Jeffrey et al, 2013Jeffrey et al, , 2014. Both post-HI and sham control animals received electrode implantation at 2-3 months of age.…”

Section: Eeg Recordings and Hippocampal Stimulationmentioning

confidence: 99%

“…Squared current pulses (durations of 0.5 ms) were generated from a Grass stimulator and delivered through an isolation unit (model S88H, Grass Medical Instruments, Warwick RI, USA). A train of high-frequency pulses (60 Hz for 2 s; at a nearmaximal intensity of 150 A; Jeffrey et al, 2014) were applied to the contralateral hippocampus every 10 min for up to 10 times until stage 5 seizures were evoked in individual mice. We used this stimulation protocol because stage 5 seizures were observed in 4/5 sham controls following 7-10 high frequency stimuli (see ''Results'').…”

Section: Eeg Recordings and Hippocampal Stimulationmentioning

confidence: 99%

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

Peng

Arora

et al. 2015

Epilepsy Research

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The regional effect of serum hormone levels on cerebral blood flow in healthy nonpregnant women

Cote

Butler

Michaud

et al. 2021

Human Brain Mapping

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Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on the cerebrovascular system in humans remains largely unknown. To address this, we used a multi-modal magnetic resonance imaging (MRI) approach to investigate the link between serum hormones in the follicular phase and luteal phase of the menstrual cycle (MC) with measures of cerebrovascular function (cerebral blood flow [CBF]) and structure (intracranial artery diameter). Fourteen naturally cycling women were recruited and assessed at two-time points of their MC. CBF was derived from pseudo-continuous arterial spin labeling while diameters of the internal carotid and basilar artery was assessed using time of flight magnetic resonance angiography, blood samples were performed after the MRI. Results show that PROG and EST had opposing and spatially distinct effects on CBF: PROG correlated negatively with CBF in anterior brain regions (r = À.86, p < .01), while EST correlations were positive, yet weak and most prominent in posterior areas (r = .78, p < .01). No significant correlations between either hormone or intracranial artery diameter were observed. These results show that EST and PROG have opposing and regionally distinct effects on CBF and that this relationship is likely not due to interactions with large intracranial arteries. Considering that CBF in healthy women appears tightly linked to their current hormonal state, future studies should consider assessing MCrelated hormone fluctuations in the design of functional MRI studies in this population.

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Novel anticonvulsive effects of progesterone in a mouse model of hippocampal electrical kindling

Cited by 23 publications

References 48 publications

Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

The regional effect of serum hormone levels on cerebral blood flow in healthy nonpregnant women

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