Article
Cell Biology
Valerie Jolivel, Susana Brun, Fabien Biname, Jeremie Benyounes, Omar Taleb, Dominique Bagnard, Jerome De Seze, Christine Patte-Mensah, Ayikoe-Guy Mensah-Nyagan
Summary: Research has shown that the neurosteroid allopregnanolone (ALLO) has a direct impact on the morphology and phagocytic function of microglial cells, potentially contributing to the development of effective strategies against neurological disorders.
Review
Medicine, General & Internal
Torbjorn Backstrom, Sahruh Turkmen, Roshni Das, Magnus Doverskog, Thomas P. Blackburn
Summary: The prevalence of cognitive dysfunction and neurodegenerative disorders is increasing with an aging population. Chronic stress and positive GABA-A receptor modulating stress steroids can provoke impaired cognition. GABA-A receptor modulating steroid antagonists can block the negative cognitive effects of these steroids.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Julia Bukanova, Elena Solntseva, Rodion Kondratenko, Eva Kudova
Summary: Epi is a positive modulator of GABA-induced chloride current (I-GABA) with an EC50 of 5.7 μM in Purkinje cells and 9.3 μM in hippocampal neurons. The potentiation of I-GABA by Epi is more pronounced at low GABA concentrations.
Article
Cell Biology
Makoto Ishikawa, Sanae Takaseki, Takeshi Yoshitomi, Douglas F. Covey, Charles F. Zorumski, Yukitoshi Izumi
Summary: AlloP protects retinal ganglion cells through GABR/GABA(A) receptors in a rat glaucoma model. It induces a protective form of autophagy, preventing apoptosis and preserving RGCs in both ex vivo and in vivo models. AlloP shows potential as a therapeutic agent for glaucoma treatment.
Article
Pharmacology & Pharmacy
Vivian Wan Yu Liao, Mary Chebib, Philip Kiaer Ahring
Summary: This study successfully obtained robust α1 β2 δ and α1 β3 δ GABA(A) receptors through novel delta-containing pentameric concatenated constructs, shedding light on the pharmacology and stoichiometry of delta-containing receptors. The findings pave the way for future drug discovery efforts and provide important insights for understanding the functional properties of these receptors.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Delia Belelli, Grant D. Phillips, John R. Atack, Jeremy J. Lambert
Summary: Neurosteroids acting on GABA(A) receptors may modulate behavior by influencing neuronal signaling. Although there are challenges, the potential as new medications, especially in treating postpartum depression, is being explored.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Neurosciences
Luke Ziolkowski, Isaac Mordukhovich, Daniel M. Chen, Mariangela Chisari, Hong-Jin Shu, Peter M. Lambert, Mingxing Qian, Charles F. Zorumski, Douglas F. Covey, Steven Mennerick
Summary: Neuroactive steroids are emerging as a new class of drugs for treating neuropsychiatric disorders, with effects on ligand-gated neurotransmitter receptors being a major mechanism of action. MQ-221, a sulfated, 3 beta-hydroxy neurosteroid analogue, inhibits NMDAR function while potentiating GABA(A)R function, showing potentially unique and clinically desirable effects. It may represent a new class of compound with unique psychoactive effects and beneficial prospects for treating neuropsychiatric disorders.
Article
Pharmacology & Pharmacy
Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Takeshi Yoshitomi, Kathiresan Krishnan, Douglas F. Covey, Charles F. Zorumski, Yukitoshi Izumi
Summary: In this study, it was found that both AlloP and its enantiomer ent-AlloP have neuroprotective effects in ex vivo and in vivo rat models of ocular hypertension, with ent-AlloP being more effective in activating autophagy while having little effect on GABA receptors.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ana Paula S. Dornellas, Giovana C. Macedo, Minna H. McFarland, Alexander Gomez-A, Todd K. O'Buckley, Claudio Da Cunha, A. Leslie Morrow, Donita L. Robinson
Summary: Research has shown that allopregnanolone can reduce dopamine release in both male and female rats, with its effects modulated by sex and estrous cycle stages.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Neurosciences
Doodipala Samba Reddy, Robert H. H. Mbilinyi, Emily Estes
Summary: This article discusses the critical role of neurosteroids in postpartum depression (PPD) and introduces the breakthrough antidepressant brexanolone as a first-in-class neurosteroid therapy. PPD, a neuroendocrine disorder affecting 20% of mothers, is characterized by symptoms such as persistent sadness, fatigue, dysphoria, and disruptions in cognition, emotion, appetite, and sleep. The main pathology behind PPD is the reduction of neurosteroids after childbirth, known as neurosteroid withdrawal. Brexanolone, a progesterone-derived allopregnanolone, rapidly alleviates anxiety and mood deficits by activating GABA-A receptors, making it a transformative treatment for PPD with significant advantages over traditional antidepressants.
PSYCHOPHARMACOLOGY
(2023)
Review
Clinical Neurology
Todd A. Verdoorn, Tom J. Parry, Graziano Pinna, Jonathan Lifshitz
Summary: Traumatic brain injury (TBI) leads to various pathological effects on multiple biochemical and physiological systems in and outside the brain. The recovery of patients is hindered by early brain edema, inflammation, cell death, and neurovascular disruption. Drug treatments targeting these deficits are being developed, and it is likely that effective therapy would require interruption of the TBI-induced pathological processes by either a combination of drugs or a single pleiotropic drug. The complex neurosteroid system offers potential options for the research and development of pleiotropic drug treatments for TBI.
Article
Biochemistry & Molecular Biology
Julia V. Bukanova, Rodion V. Kondratenko, Elena I. Solntseva
Summary: This study investigates the interaction between positive allosteric modulators (PAMs) and competitive antagonists of GABA(A)Rs, demonstrating unblocking effects and revealing an allosteric relationship between these two types of compounds.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Behavioral Sciences
Juan Francisco Rodriguez-Landa, Fabiola Hernandez-Lopez, Lucia Martinez-Mota, Damiana Scuteri, Blandina Bernal-Morales, Eduardo Rivadeneyra-Dominguez
Summary: The study found that intrahippocampal microinjections of chrysin can affect anxiety-like behavior in female rats by regulating the GABA(A)/benzodiazepine receptor complex. The effects of the treatment vary across different estrous cycle phases.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Obstetrics & Gynecology
Anton Sandstrom, Marie Bixo, Torbjoern Backstrom, Anna Moller, Sahruh Turkmen
Summary: A study found that women with painful endometriosis have lower sensitivity to GABA(A) receptor stimulation compared to healthy controls. This indicates altered GABA(A) receptor function in the context of endometriosis-related pain.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2023)
Article
Biochemistry & Molecular Biology
Kelly B. Ahern, Juan F. Garzon, Deniz Yuruk, Maria Saliba, Can Ozger, Jennifer L. Vande L. Voort, Paul E. Croarkin
Summary: This study aimed to assess the association between LICI and CSP in youths. The results showed that there was no correlation between CSP and LICI in our sample, despite previous studies suggesting that they measure GABA(B) receptor-mediated activity.
