Jana Veliskova

Departments of Neurology & Neuroscience

Associate Professor
Cellular and molecular mechanisms of seizure-induced damage; hormonal regulation of seizure control; neuroprotective effects of sex hormones; estrogen-neuropeptide interaction; sex hormones and GABAergic neurotransmission.

Kennedy Center
Room 312
(718) 430-4277

Hormonal regulation of seizure control and neuroprotective effects of sex steroids

The laboratory is interested in mechanisms by which sex hormones influence seizures and their consequences using rat seizure models.

1. Estrogens affect brain development and ongoing modulation/excitability of the nervous system. The role of estrogens on seizures is controversial. Generally it is believed that estrogens increase seizure susceptibility and thus women with epilepsy are advised not to use hormonal replacement therapy. However, estrogens have neuroprotective effects and support neuronal survival. One of the most common epileptic syndromes, the temporal lobe epilepsy (TLE) is often accompanied by extensive neuronal damage in the hippocampus known as hippocampal sclerosis. Neuronal loss leads to reorganization of hippocampal axon circuits, which then contribute to further seizure genesis and intractability. Women with TLE often have reproductive endocrine disorders resulting in abnormal levels of estrogens or progesterone. Restoration of normal ovulatory cycles in these female patients is also an effective seizure therapy. This observation suggests involvement of female sex hormones in TLE. Results from our studies show that estrogens have neuroprotective effects on seizure-induced damage and thus women with TLE may benefit from estrogen therapy. Moreover, we found that low, physiologic levels of estrogen do not increase seizure susceptibility and may even decrease it. The major focus is to determine the mechanisms, by which the estrogen produces these neuroprotective effects. Our data show that interactions between estrogen and neuropeptides may be involved. Further examination of the role of estrogen in seizures and mechanisms by which estrogen exerts its effects will significantly impact the treatment of women with epilepsy. Estrogen-neuropeptide interactions within the hippocampus are also important for understanding depression/anxiety, feeding behavior, memory processing, and cognition.

2. Our second project focuses on the role of perinatal testosterone surge on differentiation of the substantia nigra. Several brain regions are different between males and females (sexual dimorphism). Some of the sexually dimorphic structures are involved in seizure generation (amygdala, hippocampus, hypothalamus) or seizure control (substantia nigra). We found that the GABAergic neurotransmitter system has sexually dimorphic features within the substantia nigra pars reticulata, and testosterone plays a role in this differentiation. Our goal is to determine the effects of testosterone on development and maturation of the nigral seizure-controlling network.

 

Selected Publications

Velísková, J., Velísek, L., Galanopoulou, A.S., and Sperber, E.F.: Neuroprotective effects of estrogens on hippocampal cells in adult female rats following status epilepticus. Epilepsia, 41 Suppl.6:S30-35, (2000).

Velísková, J. and Moshé, S.L.: Sexual dimorphism and developmental regulation of substantia nigra function. Ann. Neurol., 50:596-601, (2001).

Ravizza, T., Galanopoulou, A.S., Velísková, J., and Moshé, S.L: Sex differences in androgen and estrogen receptor expression in rat substantia nigra during development: An immunohistochemical study. Neuroscience, 115:685-96, (2002).

Velísek, L. and Velísková, J.: Estrogen treatment protects GABAB inhibition in the dentate gyrus of female rats after kainic acid-induced status epilepticus. Epilepsia, 44 Suppl.5:146-51,(2002).

Ravizza, T., Velísková, J., and Moshé, S.L: Testosterone regulates androgen and estrogen receptor immunoreactivity in rat substantia nigra pars reticulata. Neurosci. Lett., 338:57-61, (2003).

Galanopoulou, A.S., Alm Medina, E. and Velísková, J.: Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats. Neurosci. Lett. 342:201-205, (2003).

Ravizza, T., Friedman, L.K., Moshé, S.L., and Velísková, J.: Sex and site-specific differences in GABAAergic system in rat substantia nigra pars reticulata. Intl. J. Dev. Neurosci., 21(5):245-254, (2003).

Rizzi, M., Perego, C., Aliprandi, M., Richichi, C., Ravizza, T., Colella, D., Velísková, J., Moshé, S.L, De Simoni, M.G., and Vezzani, A.: Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development. Neurobiol. Dis., 14:494-503, (2003).

Velísková, J.: Effects of sex hormones in the CNS. Cs. Fyziol., in press.

Haut, S., Velísková, J., and Moshé, S.L: Relative vulnerability of immature and adult brain to the effects of seizures: human and animal studies. Lancet Neurol., in press.