Sex dimorphism in seizure-controlling networks

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 GABAA 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 [14C]2-deoxyglucose autoradiography. These involve sex-specific patterns in the developmental changes in the structure or physiology or GABAA receptors or of other subcortical structures (e.g., locus coeruleus, hippocampus) that may affect the function of seizure-controlling networks.

Original languageEnglish (US)
Pages (from-to)144-152
Number of pages9
JournalNeurobiology of Disease
Volume72
Issue numberPB
DOIs
StatePublished - May 20 2014

Fingerprint

Sex Characteristics
Seizures
Muscimol
Flurothyl
GABA-A Receptor Agonists
Gonadal Hormones
Reticular Formation
Locus Coeruleus
Deoxyglucose
Androgen Receptors
GABA-A Receptors
Pars Reticulata
Basal Ganglia
Autoradiography
Thalamus
Anticonvulsants
Hippocampus
Animal Models
Brain

Keywords

  • Androgen receptor
  • Critical period
  • Dimorphism
  • Epilepsy
  • Estrogen receptor
  • GABA receptor
  • Hippocampus
  • Immature
  • KCC2
  • Locus Coeruleus
  • Rat
  • Seizures
  • Substantia nigra pars reticulata

ASJC Scopus subject areas

  • Neurology

Cite this

Sex dimorphism in seizure-controlling networks. / Giorgi, Fillippo Sean; Galanopoulou, Aristea S.; Moshe, Solomon L.

In: Neurobiology of Disease, Vol. 72, No. PB, 20.05.2014, p. 144-152.

Research output: Contribution to journalArticle

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