Dr. Aristea S. Galanopoulou

Assistant Professor

Kennedy Center
Room 311
(718) 430-3791

 

The role of cation chloride cotransporters and GABA A receptors in seizure susceptibility of the neonatal brain and sexual differentiation of the brain; consequences of neonatal seizures; pathophysiology of Rett syndrome.

The maturation of GABA A receptor-mediated signaling from excitatory to inhibitory is an age-related process controlled by cation chloride cotransporters, such as KCC2. As a result, GABA exerts dual functions, being an important neurotrophic factor during early development and the principal inhibitory neurotransmitter of the mature central nervous system. We have shown that this maturation process occurs earlier in certain female brain structures and is under the control of gonadal hormones. Moreover, not only GABA but also estrogens activate different signaling cascades in neurons with excitatory vs inhibitory GABA A receptor function. These suggest that GABA A receptors are critical in promoting the sexual differentiation of the brain, both via direct actions as well as by defining the ontogenetically early sensitive period to certain estrogen actions.

Work in this laboratory aims to further characterize the physiological consequences of the age and gender related differences in GABA A receptor signaling, specifically in relation to how differences in or aberrant maturation of the GABA A receptor system alters the differentiation of the neonatal brain. The clinically relevant endpoints are to: (1) identify molecular factors or physiological parameters that could be important modulators of the susceptibility to and consequences of neonatal seizures, allowing specific genetic or epigenetic interventions to ameliorate the incidence and outcome of epilepsy; (2) determine whether abnormal maturation of the GABA A receptor system in the substantia nigra could contribute to the pathogenesis of the abnormal motoric function of patients with Rett syndrome, a major cause of mental retardation and epilepsy in girls. Students interested in these projects will gain exposure to a variety of in vivo and in vitro techniques combining molecular biology and electrophysiology. These projects are funded by NIH / NINDS and the Rett Syndrome Research Foundation.

Selected Publications

Galanopoulou AS. GABA A receptors as broadcasters of sexually differentiating signals in the brain. Epilepsia 46 (Suppl 5): 107-12 (2005).

Galanopoulou AS, Moshé SL. Role of sex hormones in the sexually dimorphic expression of KCC2 in rat substantia nigra. Exp Neurol, 184(2): 1003-1009, (2003).

Galanopoulou AS, Kyrozis A, Claudio OI, Stanton PK, Moshé SL. Sex-specific KCC2 expression and GABA A receptor function in rat substantia nigra. Exp Neurol, 183: 628-637, (2003).

Galanopoulou AS, Medina Alm E, Veliskova, J. Estradiol reduces seizure-induced hippocampal injury in ovariectomized female rats but not in male rats. Neurosci Lett, 342 (3) : 201-5, (2003).

Ravizza T, Galanopoulou AS, Veliskova J, Moshé SL. Sex differences in androgen and estrogen receptor expression in rat substantia nigra during development: an immunohistochemical study. Neuroscience, 115(3):685-696, (2002).

Galanopoulou AS, Vidaurre J, Moshé SL. Under what circumstances can seizures produce hippocampal injury: evidence for age-specific effects. Developmental Neuroscience 24(5): 355-363, (2002).

Galanopoulou AS, Bojko A, Lado F, Moshé SL. The spectrum of neuropsychiatric abnormalities associated with electrical status epilepticus in sleep. Brain & Development, vol. 22: 279-295, (2000).