Among neurosteroids, allopregnanolone is the most potent endogenous positive modulator of GABA(A) receptors, and disturbances in its release may play a role in pathomechanism of some neurological and psychiatric disorders. In contrast to a large body of evidence on allopregnanolone involvement in pathogenesis of epilepsy, no data are available on its role in pseudoseizures. Therefore, the aim of the present study was to find out whether pseudoseizures are associated with changes in plasma allopregnanolone level in pediatric patients. This study was carried out on 45 children with video EEG-diagnosed pseudoseizures, divided into three groups according to results of placebo test i.e: (I) children with pseudoseizures attacks without antiepileptic drug treatment; (II) children with pseudoseizures attacks and treated with antiepileptic drugs; (III) children without pseudoseizures attacks and no treatment. Allopregnanolone level was estimated by radioimmunoassay in blood samples collected before and after provoking pseudoseizures by placebo. No significant changes have been found in allopregnanolone level between all experimental groups. This suggests that in contrast to epileptic seizures, during pseudoseizures no compensatory increase in the endogenous antiepileptic and anxiolytic neurosteroid release occurs. The low level of allopregnanolone may have a detrimental effect on GABAergic inhibitory system in the brain aggravating stress response and promoting pseudoseizure occurrence. On the other hand, the clinical value of allopregnanolone plasma level as a biomarker distinguishing between epileptic and pseudoseizures remains questionable due to its high inter-individual differences.
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Sci Adv
January 2025
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
A key response to acute stress is the increased brain synthesis of the neurosteroid allopregnanolone (AP). Although the rate-limiting step of this reaction is catalyzed by 5α-reductase (5αR), the role of its two primary isoenzymes, 5αR1 and 5αR2, in stress reactivity remains unclear. Here, we found that acute stress led to increased levels of 5αR2, but not 5αR1, in the medial prefrontal cortex (mPFC) of male, but not female, rats.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
An aberrant pro-inflammatory microglia response has been associated with most neurodegenerative disorders. Identifying microglia druggable checkpoints to restore their physiological functions is an emerging challenge. Recent data have shown that microglia produce de novo neurosteroids, endogenous molecules exerting potent anti-inflammatory activity.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
Zebrafish Translational Medical Research Center, Korea University, Ansan, Gyeonggi-do, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea. Electronic address:
Citronellol is widely utilized in consumer products, including cosmetics, fragrances, and household items. However, despite being considered a relatively safe chemical, the health effects and toxicity mechanisms associated with exposure to high concentrations of citronellol, based on product content, remain inadequately understood. Here, we aimed to analyze the neurological effects of citronellol in zebrafish larvae using behavioral and histological analyses and elucidate the mechanisms underlying its neurotoxicity in vivo.
View Article and Find Full Text PDFJ Comput Neurosci
December 2024
Department of Applied Mathematics, and Centre for Theoretical Neuroscience, University of Waterloo, 200 University Avenue W, Waterloo, N2L 3G1, ON, Canada.
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