Sex dimorphism in seizure-controlling networks.
Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamus, reticular formation nuclei, and structures belonging to the basal ganglia. In animal models, the substantia nigra pars reticulata (SNR) is the best studied of these areas, given its relevant role in the expression and control of seizures throughout development in the rat. Studies with bilateral infusions of the GABA(A) receptor agonist muscimol have identified distinct roles of the anterior or posterior rat SNR in flurothyl seizure control, that follow sex-specific maturational patterns during development. These studies indicate that (a) the regional functional compartmentalization of the SNR appears only after the third week of life, (b) only the male SNR exhibits muscimol-sensitive proconvulsant effects which, in older animals, is confined to the posterior SNR, and (c) the expression of the muscimol-sensitive anticonvulsant effects become apparent earlier in females than in males. The first three postnatal days are crucial in determining the expression of the muscimol-sensitive proconvulsant effects of the immature male SNR, depending on the gonadal hormone setting. Activation of the androgen receptors during this early period seems to be important for the formation of this proconvulsant SNR region. We describe molecular/anatomical candidates underlying these age- and sex-related differences, as derived from in vitro and in vivo experiments, as well as by [(14)C]2-deoxyglucose autoradiography. These involve sex-specific patterns in the developmental changes in the structure or physiology or GABA(A) receptors or of other subcortical structures (e.g., locus coeruleus, hippocampus) that may affect the function of seizure-controlling networks.
Department of Clinical and Experimental Medicine, Section of Neurology, University of Pisa-Pisa University Hospital, I56126 Pisa, Italy. Electronic address: giorgifs@gmail.com.
Fillippo Sean
FS
Giorgi
Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Montefiore Epilepsy Management Center, and Dominick P. Purpura Department of Neuroscience, Bronx, NY, 10461, USA.
Aristea S
AS
Galanopoulou
Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Montefiore Epilepsy Management Center, and Dominick P. Purpura Department of Neuroscience, Bronx, NY, 10461, USA; Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 10461, USA.
Solomon L
SL
Moshé
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015984:Causality; D005260:Female; D006801:Humans; D008297:Male; D018080:Receptors, GABA-B / Q000378:metabolism; D012640:Seizures / Q000473:pathology*; D012727:Sex Characteristics
D018080:Receptors, GABA-B
Androgen receptor; Critical period; Dimorphism; Epilepsy; Estrogen receptor; GABA receptor; Hippocampus; Immature; KCC2; Locus Coeruleus; Rat; Seizures; Substantia nigra pars reticulata