Sex differences in models of temporal lobe epilepsy: role of testosterone

Mejías-Aponte, Carlos A.; Jiménez‐Rivera, Carlos A.; Segarra, Annabell C.

doi:10.1016/s0006-8993(02)02691-4

Cited by 106 publications

(70 citation statements)

References 55 publications

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“…Sex differences in plasma testosterone levels at baseline were comparable to the findings of other studies [14,15]. Plasma cortisol levels at baseline tended to be non-significantly higher in women.…”

Section: Discussionsupporting

confidence: 84%

The effect of mental rotation on changes in plasma testosterone and cortisol levels

Durdiaková¹,

Hodosy²,

Kubranská

et al. 2012

Open Life Sciences

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Testosterone level has an influence on cognitive functions, especially spatial abilities. The relationship is, however, bidirectional and brain activity also affects testosterone levels. The aim of this study was to analyze the effects of an intensive 3D mental rotation task on testosterone levels in young healthy men and women. In the mental rotation task, men reached a higher top score (P=0.027) and total score (P=0.004) compared to women. In 8 out of 9 women (P=0.008) but not in men (P=0.129) testosterone levels decreased after one hour of mental rotation testing. A significant gender difference was shown (P<0.0001). In all women, plasma cortisol levels was significantly lower after testing (P=0.004). In men cortisol levels decreased in 7 out of 9 subjects (P=0.039). A significant gender difference was not found (P=0.19). No association was found in women between baseline testosterone levels and mental rotation total score (P=0.810). In men there was a positive correlation between baseline testosterone and mental rotation total score (P=0.015). A significant difference gender difference was seen in the association between testosterone and mental rotation score (P<0.05). Mental rotation stimuli caused significant changes in hormonal levels of testosterone and cortisol. A gender-specific response was detected in testosterone fluctuation.

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Section: Discussionsupporting

confidence: 84%

The effect of mental rotation on changes in plasma testosterone and cortisol levels

Durdiaková¹,

Hodosy²,

Kubranská

et al. 2012

Open Life Sciences

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“…Although still somewhat controversial, many studies have shown that the expression of AMPA-, KA-and NMDA-sensitive receptors as well as the GABA A receptor is either constant or variably diminished in many different brain regions including the hippocampus during aging (Gonzales et al, 1991;Pittaluga et al, 1993;Le Jeune et al, 1996;Nicolle et al, 1996;EcklesSmith et al, 2000;Kuehl-Kovarik et al, 2000;Magnusson, 2000;Sonntag et al, 2000;Wenk and Barnes, 2000;Adams et al, 2001;Clayton and Browning, 2001;Clayton et al, 2002;Lerma et al, 2001). Differences in a variety of other factors, including voltage-gated calcium channels (Vigues et al, 1999;Kelly et al, 2003), androgen levels (Mejias-Aponte et al, 2002;Ramsden et al, 2003;Ciriza et al, 2004), and GABA receptor function (MacGregor et al, 1997;Ma et al, 2001) which have been shown to modulate kainate-induced seizure activity in young animals, may modulate susceptibility in aged animals as well.…”

Section: Discussionmentioning

confidence: 99%

Effect of age on kainate-induced seizure severity and cell death

et al. 2008

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While the onset and extent of epilepsy increases in the aged population, the reasons for this increased incidence remain unexplored. The present study used two inbred strains of mice (C57BL/6J and FVB/NJ) to address the genetic control of age-dependent neurodegeneration by building upon previous experiments that have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death. We determined if seizure induction and seizure-induced cell death are affected differentially in young adult, mature, and aged male C57BL/6J and FVB/NJ mice administered the excitotoxin, kainic acid. Dose response testing was performed in three-four groups of male mice from each strain. Following kainate injections, mice were scored for seizure activity and brains from mice in each age group were processed for light microscopic histopathologic evaluation seven days following kainate administration to evaluate the severity of seizure-induced brain damage. Irrespective of the dose of kainate administered or the age group examined, resistant strains of mice (C57BL/6J) continued to be resistant to seizure-induced cell death. In contrast, aged animals of the FVB/NJ strain were more vulnerable to the induction of behavioral seizures and associated neuropathology after systemic injection of kainic acid than young or middle-aged mice.Results from these studies suggest that the age-related increased susceptibility to the neurotoxic effects of seizure induction and seizure-induced injury is regulated in a strain-dependent manner, similar to previous observations in young adult mice. Keywords mouse strain; excitotoxicity; kainic acid; epilepsy; cell death; aging Knowledge about the influence of aging on the susceptibility of the brain to seizure disorders is of critical importance in geriatric medicine and public health. Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide and with a 2-3% life time risk of being given a diagnosis of epilepsy (Browne and Holmes, 2001). Currently it is well known that there is a significant incidence of epilepsy in children. However, less clearly recognized but of increasing importance is the significant incidence of epilepsy in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the elderly population. Recent studies in the United States and Europe indicate that the agespecific incidence of epilepsy is higher in those over the age of 65 years than in those in the first decade of life (Talli...

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“…The potential molecular pathways for the testosterone modulation of seizure activity are illustrated in Figure 3. Testosterone is known to produce both proconvulsant and anticonvulsant effects depending on the animal model and the seizure type (Werboff and Havlena, 1968;Thomas and McLean, 1991;Frye and Reed, 1998;Pesce et al, 2000;Mejias-Aponte et al, 2002). Both animal and clinical studies show that testosterone enhances seizure activity by metabolism to estrogens (Isojarvi et al, 1988;Thomas and Yang, 1991;Herzog et al, 1998;Edwards et al, 1999;El-Khayat et al, 2003).…”

Section: Effect Of Testosterone On Seizure Susceptibilitymentioning

confidence: 99%

Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids

Reddy¹

2008

Neurochemistry International

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Steroid hormones play a key role in the pathophysiology of several brain disorders. Testosterone modulates neuronal excitability, but the underlying mechanisms are obscure. There is emerging evidence that testosterone-derived "androgenic neurosteroids", 3α-androstanediol and 17β-estradiol, mediate the testosterone effects on neural excitability and seizure susceptibility. Testosterone undergoes metabolism to neurosteroids via two distinct pathways. Aromatization of the A-ring converts testosterone into 17β-estradiol. Reduction of testosterone by 5α-reductase generates 5α-dihydrotestosterone, which is then converted to 3α-androstanediol, a powerful GABA A receptormodulating neurosteroid with anticonvulsant properties. Although the 3α-androstanediol is an emerging neurosteroid in the brain, there is no specific and sensitive assay for determination of 3α-androstanediol in biological samples. This article describes the development and validation of mass spectrometric assay of 3α-androstanediol, and the molecular mechanisms underlying the testosterone modulation of seizure susceptibility. A liquid chromatography-tandem mass spectrometry assay to measure 3α-androstanediol is validated with excellent linearity, specificity, sensitivity, and reproducibility. Testosterone modulation of seizure susceptibility is demonstrated to occur through its conversion to neurosteroids with "anticonvulsant" and "proconvulsant" actions and hence the net effect of testosterone on neural excitability and seizure activity depends on the levels of distinct testosterone metabolites. The proconvulsant effect of testosterone is associated with increases in plasma 17β-estradiol concentrations. The 5α-reduced metabolites of testosterone, 5α-dihydrotestosterone and 3α-androstanediol, had powerful anticonvulsant activity. Overall, the testosterone-derived neurosteroids 3α-androstanediol and 17β-estradiol could contribute to the net cellular actions of testosterone in the brain. Because 3α-androstanediol is a potent positive allosteric modulator of GABA A receptors, it could serve as an endogenous neuromodulator of neuronal excitability in men. The 3α-androstanediol assay is an important tool in this area because of the growing interest in the potential to use adjuvant aromatase inhibitor therapy to improve treatment of epilepsy.

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Sex differences in models of temporal lobe epilepsy: role of testosterone

Cited by 106 publications

References 55 publications

The effect of mental rotation on changes in plasma testosterone and cortisol levels

The effect of mental rotation on changes in plasma testosterone and cortisol levels

Effect of age on kainate-induced seizure severity and cell death

Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids

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