ArticleBMC neuroscience2008
Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential.
Article in BMC neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study.Molecular neurobiology · 2019Trial
- GABADrug design, development and therapy · 2026Review
- Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution.Journal of neuroendocrinology · 2025Review
- Neuroactive steroids in the programming of neurodevelopment: implications of maternal obesity.Frontiers in endocrinology · 2025Review
- Allopregnanolone pleiotropic action in neurons and astrocytes: calcium signaling as a unifying mechanism.Frontiers in endocrinology · 2023Article
- Golexanolone, a GABACNS neuroscience & therapeutics · 2022Article
- Lack of placental neurosteroid alters cortical development and female somatosensory function.Frontiers in endocrinology · 2022Article
- Relationship between adult subventricular neurogenesis and Alzheimer's disease: Pathologic roles and therapeutic implications.Frontiers in aging neuroscience · 2022Review
- Structure-Activity Relationship of Neuroactive Steroids, Midazolam, and Perampanel Toward Mitigating Tetramine-Triggered Activity in Murine Hippocampal Neuronal Networks.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Allopregnanolone Reverses Bioenergetic Deficits in Female Triple Transgenic Alzheimer's Mouse Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity.International journal of molecular sciences · 2019Article
- Allopregnanolone Modulates GABAAR-Dependent CaMKIIδ3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage.Frontiers in cellular neuroscience · 2019Article
- Neurosteroid Metabolites of Gonadal Steroid Hormones in Neuroprotection: Implications for Sex Differences in Neurodegenerative Disease.Frontiers in molecular neuroscience · 2018Review
- Calcium-engaged Mechanisms of Nongenomic Action of Neurosteroids.Current neuropharmacology · 2017Review
- Article
- Allopregnanolone and neurogenesis in the nigrostriatal tract.Frontiers in cellular neuroscience · 2014Review
- Frontiers in therapeutic development of allopregnanolone for Alzheimer's disease and other neurological disorders.Frontiers in cellular neuroscience · 2014Review
- Neurosteroids as regenerative agents in the brain: therapeutic implications.Nature reviews. Endocrinology · 2013Review
- Therapeutic effects of progesterone and its metabolites in traumatic brain injury may involve non-classical signaling mechanisms.Frontiers in neuroscience · 2013Article
- Allopregnanolone increases the number of dopaminergic neurons in substantia nigra of a triple transgenic mouse model of Alzheimer's disease.Current Alzheimer research · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFactors that regulate intracellular calcium concentration are known to play a critical role in brain function and neural development, including neural plasticity and neurogenesis. We previously demonstrated that the neurosteroid allopregnanolone (APalpha; 5alpha-pregnan-3alpha-ol-20-one) promotes neural progenitor proliferation in vitro in cultures of rodent hippocampal and human cortical neural progenitors, and in vivo in triple transgenic Alzheimer's disease mice dentate gyrus. We also found that APalpha-induced proliferation of neural progenitors is abolished by a calcium channel blocker, nifedipine, indicating a calcium dependent mechanism for the proliferation.
methodsIn the present study, we investigated the effect of APalpha on the regulation of intracellular calcium concentration in E18 rat hippocampal neurons using ratiometric Fura2-AM imaging.
resultsResults indicate that APalpha rapidly increased intracellular calcium concentration in a dose-dependent and developmentally regulated manner, with an EC50 of 110 +/- 15 nM and a maximal response occurring at three days in vitro. The stereoisomers 3beta-hydroxy-5alpha-hydroxy-pregnan-20-one, and 3beta-hydroxy-5beta-hydroxy-pregnan-20-one, as well as progesterone, were without significant effect. APalpha-induced intracellular calcium concentration increase was not observed in calcium depleted medium and was blocked in the presence of the broad spectrum calcium channel blocker La3+, or the L-type calcium channel blocker nifedipine. Furthermore, the GABAA receptor blockers bicuculline and picrotoxin abolished APalpha-induced intracellular calcium concentration rise.
conclusionCollectively, these data indicate that APalpha promotes a rapid, dose-dependent, stereo-specific, and developmentally regulated increase of intracellular calcium concentration in rat embryonic hippocampal neurons via a mechanism that requires both the GABAA receptor and L-type calcium channel. These data suggest that APalpha-induced intracellular calcium concentration increase serves as the initiation mechanism whereby APalpha promotes neurogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.