Hormonal Therapy for Epilepsy

Stevens, Scott J.; Harden, Cynthia L.

doi:10.1007/s11910-011-0196-9

Cited by 20 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, 5α-DHP inhibited both components of seizures (Lonsdale et al, 2006). Growing evidence suggests that anticonvulsive and neuroprotective properties of PROG are mediated by its metabolites 5α-DHP and ALLO, positive modulators of GABA A receptors (Reddy, 2004; Ciriza et al, 2006; Verrotti et al, 2010; Stevens and Harden, 2011). ALLO itself protected against picrotoxin-induced neuronal cell death (Brinton, 1994).…”

Section: Progesterone and Derivativesmentioning

confidence: 99%

Neuroprotective Actions of Neurosteroids

Borowicz¹,

Piskorska²,

Banach³

et al. 2011

Front. Endocrin.

View full text Add to dashboard Cite

Neurosteroids were initially defined as steroid hormones locally synthesized within the nervous tissue. Subsequently, they were described as steroid hormone derivatives that devoid hormonal action but still affect neuronal excitability through modulation of ionotropic receptors. Neurosteroids are further subdivided into natural (produced in the brain) and synthetic. Some authors distinguish between hormonal and regular neurosteroids in the group of natural ones. The latter group, including hormone metabolites like allopregnanolone or tetrahydrodeoxycorticosterone, is devoid of hormonal activity. Both hormones and their derivatives share, however, most of the physiological functions. It is usually very difficult to distinguish the effects of hormones and their metabolites. All these substances may influence seizure phenomena and exhibit neuroprotective effects. Neuroprotection offered by steroid hormones may be realized in both genomic and non-genomic mechanisms and involve regulation of the pro- and anti-apoptotic factors expression, intracellular signaling pathways, neurotransmission, oxidative, and inflammatory processes. Since regular neurosteroids show no affinity for steroid receptors, they may act only in a non-genomic mode. Multiple studies have been conducted so far to show efficacy of neurosteroids in the treatment of the central and peripheral nervous system injury, ischemia, neurodegenerative diseases, or seizures. In this review we focused primarily on neurosteroid mechanisms of action and their role in the process of neurodegeneration. Most of the data refers to results obtained in experimental studies. However, it should be realized that knowledge about neuroactive steroids remains still incomplete and requires confirmation in clinical conditions.

show abstract

Section: Progesterone and Derivativesmentioning

confidence: 99%

Neuroprotective Actions of Neurosteroids

Borowicz¹,

Piskorska²,

Banach³

et al. 2011

Front. Endocrin.

View full text Add to dashboard Cite

show abstract

“…However, in men, androgen ablation therapy for prostate cancer leads to few or no significant deficits in cognitive performance (Nelson et al, 2008; Alibhai et al, 2010a; Alibhai et al, 2010b; Matousek and Sherwin, 2010). The reduced levels of androgens in aging men are often considered to be a contributing factor to diseases that increase with age such as Alzheimer’s disease (Fuller et al, 2007; Drummond et al, 2009; Barron and Pike, 2011; Luchetti et al, 2011), epilepsy (Herzog, 1991; Harden and MacLusky, 2004; 2005; Frye, 2006; Reddy, 2010; Stevens and Harden, 2011) and Parkinson’s disease (Al Sweidi et al, 2011). However, direct evidence in support of this idea, such as prevention of these diseases by androgen therapy, is generally weak, although androgens ameliorate symptoms in some instancess (Herzog, 1991; Almeida and Flicker, 2003; Cherrier et al, 2005; Harden and MacLusky, 2005; Driscoll and Resnick, 2007).…”

Section: Introductionmentioning

confidence: 99%

Testosterone Depletion in Adult Male Rats Increases Mossy Fiber Transmission, LTP, and Sprouting in Area CA3 of Hippocampus

et al. 2013

View full text Add to dashboard Cite

Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation (LTP) of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms, and found that Gdx induced a long-lasting upregulation of MF brain-derived neurotrophic factor (BDNF) immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins such as BDNF, reversed the increase in MF transmission, excitability and LTP in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metabolites dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol were examined. Exposure of slices to 50 nM DHT decreased the effects of Gdx on MF transmission but 50 nM 5α-androstane-3α,17β-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that androgens may normally be important in area CA3 to prevent hyperexcitability and aberrant axon outgrowth, but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity.

show abstract

“…Growing evidence suggests that anticonvulsive and neuroprotective properties of PROG are mediated by its metabolites 5α-DHP and ALLO, positive modulators of GABAA receptors (Stevens & Harden, 2011).…”

Section: Progesterone and Derivativesmentioning

confidence: 99%