Neuroendocrine Hormonal Conditions in Epilepsy

Hamed, Sherifa A.

doi:10.1097/nrl.0b013e3181618ada

Cited by 46 publications

(5 citation statements)

References 165 publications

(216 reference statements)

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“…Contrasting to this decrease of bioavailable testosterone, levels of corticosterone are usually greater among individuals with acquired epilepsy compared to controls [17], [35], [53], [64]. Thus, in our model, high levels of corticosterone may decrease free testosterone, but increase E 2 levels in an age-dependent fashion.…”

Section: Discussionmentioning

confidence: 67%

“…Male pups experience a surge of testosterone that occurs on days 18–19 of gestation and again during the first few hours after birth with a critical window from P0 to P2 [14], [52]. Emerging data show that testosterone and its active metabolites, estradiol and dihydrotestosterone, are important factors in both androgenization of the brain and the response to early life insults such as cerebral ischemia, trauma and seizures [53]. In general, clinical evidence and animal models indicate greater brain damage in newborn male compared to female following injury.…”

Section: Discussionmentioning

confidence: 99%

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Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

et al. 2012

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During development, the risk of developing mesial temporal lobe epilepsy (MTLE) increases when the developing brain is exposed to more than one insult in early life. Early life insults include abnormalities of cortical development, hypoxic-ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have developed a two-hit model of MTLE characterized by two early-life insults: a freeze lesion-induced cortical malformation at post-natal day 1 (P1), and a prolonged hyperthermic seizure (HS) at P10. As early life stressors lead to sexual dimorphism in both acute response and long-term outcome, we hypothesized that our model could lead to gender-based differences in acute stress response and long-term risk of developing MTLE. Male and female pups underwent a freeze-lesion induced cortical microgyrus at P1 and were exposed to HS at P10. Animals were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma corticosterone levels were used to measure stress response at P1 and P10. To confirm the role of sex steroids, androgenized female pups received daily testosterone injections to the mother pre-natally and post-natally for nine days while undergoing both insults. We demonstrated that after both insults females did not develop MTLE while all males did. This correlated with a rise in corticosterone levels at P1 following the lesion in males only. Interestingly, all androgenized females showed a similar rise in corticosterone at P1, and also developed MTLE. Moreover, we found that the cortical lesion significantly decreased the latency to generalized convulsion during hyperthermia at P10 in both genders. The cortical dysplasia volumes at adulthood were also similar between male and female individuals. Our data demonstrate sexual dimorphism in long-term vulnerability to develop epilepsy in the lesion + hyperthermia animal model of MTLE and suggest that the response to early-life stress at P1 contributes significantly to epileptogenesis in a gender-specific manner.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

et al. 2012

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“…We also demonstrated that GHSR inhibits Ca V 3.2 currents. In neurons, Ca V 3 channels control the shape and frequency of action potentials (Perez-Reyes, 2003;Zhang et al, 2013), and changes in channel activity due to alternative splicing (Murbartian et al, 2004;Latour et al, 2004) or nonsense mutations (Powell et al, 2009) are responsible for pathophysiological states, such as epilepsy (Hamed, 2008). Yet, the mechanisms that control Ca V 3 trafficking and surface membrane stability are largely unknown (Zhang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Constitutive activity of the Ghrelin receptor reduces surface expression of voltage-gated Ca2+ channels in a CaVβ-dependent manner

Mustafá

Soto

Damonte

et al. 2017

Journal of Cell Science

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Voltage-gated Ca 2+ (Ca V ) channels couple membrane depolarization to Ca 2+ influx, triggering a range of Ca 2+-dependent cellular processes. Ca V channels are, therefore, crucial in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of Ca V channels. GPCRdependent mechanisms that downregulate Ca V channel expression levels are observed in many neurons but are, by comparison, less studied. Here we show that the growth hormone secretagogue receptor type 1a (GHSR), a GPCR, can inhibit the forwarding trafficking of several Ca V subtypes, even in the absence of agonist. This constitutive form of GPCR inhibition of Ca V channels depends on the presence of a Ca V β subunit. Ca V β subunits displace Ca V α 1 subunits from the endoplasmic reticulum. The actions of GHSR on Ca V channels trafficking suggest a role for this signaling pathway in brain areas that control food intake, reward, and learning and memory.

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“…Animal and clinical studies have suggested that epilepsy itself may affect sperm quality, sexual function, and sex hormones [ 22 ]. The decline in sperm quality and sexual function in men with epilepsy may be related to the disruption of hypothalamic pituitary axons by cerebral epileptiform discharges, resulting in changes in sex hormone levels [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of the Effects of Valproate and Oxcarbazepine on Sexual Function, Sperm Quality, and Sex Hormones in Males with Epilepsy

Guo

Chen

et al. 2021

BioMed Research International

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Aims. Although several studies have indicated that valproate (VPA) and oxcarbazepine (OXC) cause reproductive endocrine disorders and sexual dysfunction, there remains some controversy regarding these issues in males with epilepsy. This study is aimed at evaluating the effects of VPA and OXC on sexual function, sperm quality, and sex hormones in young males with epilepsy. Methods. Males with newly diagnosed epilepsy treated with VPA and OXC were recruited, and sexual function questionnaires (International Index of Erectile Function-5 (IIEF-5)), sperm quality, and sex hormone levels were assessed before treatment and at 6 months after treatment with VPA or OXC monotherapy. Results. Forty-four young males with epilepsy (23 treated with VPA, 21 treated with OXC) and 30 age-matched healthy individuals were recruited for our study. The sexual function, sperm quality, marriage rate, and fertility rate of these young males with epilepsy were lower than those of healthy controls. Sperm quality were significantly reduced in young male patients after 6 months of VPA administration. The level of follicle stimulating hormone (FSH) was increased in patients after OXC treatment. Meanwhile, sexual function and sperm quality were not affected. Conclusion. Sexual function and sperm quality were reduced in young males with epilepsy. VPA may exert a negative effect on sperm quality, whereas OXC has no harmful effect on sexual function and sperm quality in young males with epilepsy.

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Neuroendocrine Hormonal Conditions in Epilepsy

Cited by 46 publications

References 165 publications

Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

Early-Life Stress Is Associated with Gender-Based Vulnerability to Epileptogenesis in Rat Pups

Constitutive activity of the Ghrelin receptor reduces surface expression of voltage-gated Ca2+ channels in a CaVβ-dependent manner

A Comparative Study of the Effects of Valproate and Oxcarbazepine on Sexual Function, Sperm Quality, and Sex Hormones in Males with Epilepsy

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