ArticleExperimental neurology2008
Androgens predispose males to GABAA-mediated excitotoxicity in the developing hippocampus.
Article in Experimental neurology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Metabolic Pattern of Brain Death-NMR-Based Metabolomics of Cerebrospinal Fluid.International journal of molecular sciences · 2025Article
- TrkB-mediated neuroprotection in female hippocampal neurons is autonomous, estrogen receptor alpha-dependent, and eliminated by testosterone: a proposed model for sex differences in neonatal hippocampal neuronal injury.Biology of sex differences · 2024Article
- Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.Antioxidants (Basel, Switzerland) · 2024Article
- Role of GABAFrontiers in cellular neuroscience · 2022Article
- Hippocampal Metabolite Profiles in Two Rat Models of Autism: NMR-Based Metabolomics Studies.Molecular neurobiology · 2020Article
- Gonadal hormone-independent sex differences in GABABritish journal of pharmacology · 2020Article
- Androgens and the developing hippocampus.Biology of sex differences · 2020Review
- Sex Differences in the Development of the Rodent Corticolimbic System.Frontiers in neuroscience · 2020Review
- Stress, sensitive periods, and substance abuse.Neurobiology of stress · 2019Review
- Neonatal Intermittent Hypoxia Induces Lasting Sex-Specific Augmentation of Rat Microglial Cytokine Expression.Frontiers in immunology · 2019Article
- Time and sex dependent effects of magnesium sulphate on post-asphyxial seizures in preterm fetal sheep.The Journal of physiology · 2018Article
- Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia-ischemia.Neuroscience · 2016Article
- Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity.American journal of obstetrics and gynecology · 2016Article
- Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI.Experimental neurology · 2016Article
- Sex differences in mitochondrial (dys)function: Implications for neuroprotection.Journal of bioenergetics and biomembranes · 2015Review
- Intrinsic excitability varies by sex in prepubertal striatal medium spiny neurons.Journal of neurophysiology · 2015Article
- Sex- and age-dependent effects of androgens on glutamate-induced cell death and intracellular calcium regulation in the developing hippocampus.Neuroscience · 2014Article
- Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.Neurobiology of disease · 2014Review
- Androgens and stroke: good, bad or indifferent?Experimental neurology · 2014Review
- Dysregulation of neonatal hippocampal cell genesis in the androgen insensitive Tfm rat.Hormones and behavior · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Clinical evidence and animal models indicate greater brain damage in newborn males following injury. In adults, glutamate is the primary source of excitotoxic cell death and the steroid, estradiol, is neuroprotective. In neonatal brain, membrane depolarization following activation of GABAA receptors is the major source of excitation. Consequent influx of calcium via L-type channels is normally trophic, but becomes excitotoxic during periods of excessive activation of GABAA receptors, such as hypoxia-ischemia, alcohol exposure and seizures. The use of sex-specific hippocampal cultures revealed greater cell death induced by the GABAA agonist, muscimol, in male- versus female-derived cultures. Pretreatment with the androgen, dihydrotestosterone (DHT) increased muscimol-induced death in both sexes. Exploration of calcium dynamics indicated that, counter to expectation, female neurons achieved higher [Ca2+]i than male, but the calcium transient duration was shorter due to faster rise and decay. However, a second exposure to muscimol within minutes of the first, caused significant attenuation of [Ca2+]i in female neurons. In contrast, while male neurons exposed to muscimol for the first time exhibited lower maximal [Ca2+]i, when exposed to muscimol again there was no attenuation in [Ca2+]i. The latter effect was induced in females by DHT, and inversely correlated with the amount of gamma2 subunit of the GABAA receptor. This novel effect of androgen on GABA-mediated excitotoxicty suggests a unique opportunity for a sex-specific therapeutic approach involving antagonism of the androgen receptor in neonatal males at risk for brain injury.
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