Review
Biochemistry & Molecular Biology
Marcel P. Goldschen-Ohm
Summary: This article reviews the mechanistic interpretations of functional and structural evidence for the action of benzodiazepines on GABA(A)(alpha 1)(2)(beta X)(2)(gamma 2)(1) receptors.
Article
Biochemistry & Molecular Biology
Sara K. S. Bengtsson, Jessica Sjostedt, Evgenya Malinina, Roshni Das, Magnus Doverskog, Maja Johansson, David Haage, Torbjorn Backstrom
Summary: Through in vitro and in vivo experiments, it was found that GR3027 has inhibitory effects on GABAA receptors, indicating its potential therapeutic value.
Review
Biochemistry & Molecular Biology
Ewa Szczurowska, Eszter Szanti-Pinter, Nikolai Chetverikov, Alena Randakova, Eva Kudova, Jan Jakubik
Summary: Muscarinic acetylcholine receptors in the central nervous system have various functions, such as cognition, memory, or reward. They are potential targets for diseases like Alzheimer's, schizophrenia, addiction, epilepsy, or depression. These receptors are modulated by neurosteroids and steroid hormones, and this review focuses on their modulation in the context of CNS diseases and proposes the use of neuroactive steroids in drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Lei Wang, Douglas F. Covey, Gustav Akk, Alex S. Evers
Summary: Neurosteroids are endogenous modulators of GABA(A) receptors that regulate anxiety, pain, mood, and arousal. The 3-hydroxyl epimers, allopregnanolone (3 alpha-OH) and epi-allopregnanolone (3 beta-OH), have opposite effects on GABA(A) receptor function, acting as positive and negative allosteric modulators, respectively. A model is proposed to explain the actions of these neurosteroids based on their binding to specific sites on GABA(A) receptors, with the net functional effect being the sum of their independent effects at each site.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xi Chen, Kailiang Huang, Shenqiang Hu, Gang Lan, Xiang Gan, Shanyan Gao, Yan Deng, Jiwei Hu, Liang Li, Bo Hu, Hua He, Hehe Liu, Lu Xia, Jiwen Wang
Summary: This study revealed the regulatory mechanisms of FASN on the function of ovarian granulosa cells. It was found that FASN promotes proinflammatory factors expression through different signaling pathways and triggers necroptosis and apoptosis. Additionally, FASN affects the demand of granulosa cells for 5-HT by altering metabolic pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Ana M. Marileo, Javiera Gavilan, Victoria P. San Martin, Cesar O. Lara, Anggelo Sazo, Carola Munoz-Montesino, Patricio A. Castro, Carlos F. Burgos, Elias Leiva-Salcedo, Luis G. Aguayo, Gustavo Moraga-Cid, Jorge Fuentealba, Gonzalo E. Yevenes
Summary: Gelsemium elegans plant preparations have beneficial activity against common diseases, but their clinical use is limited by toxicity. Gelsemine, a major alkaloid in Gelsemium plants, displays therapeutic and toxic actions, but the molecular targets are unclear.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ki-Kwang Oh, Md Adnan, Dong-Ha Cho
Summary: This study investigated the pharmacological mechanisms, key targets, and potential drugs of antihistamines for treating COVID-19 using network pharmacology. Through molecular docking tests and network analysis, the most significant antihistamines, core targets, and the neuroactive ligand-receptor interaction pathway were identified. These findings provide scientific evidence for further research.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Antonella Rosario Ramona Caceres, Fiorella Campo Verde Arbocco, Daniela Alejandra Cardone, Maria de los Angeles Sanhueza, Marilina Casais, Adriana Soledad Vega Orozco, Myriam Raquel Laconi
Summary: Allopregnanolone (ALLO) participates in the peripheral neural modulation of ovarian physiology, directly interacting with ovarian tissue to modulate key mechanisms involved in normal and pathological processes in a dose-dependent manner.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Behavioral Sciences
Gabriele Floris, Gino Paolo Asuni, Giuseppe Talani, Francesca Biggio, Maria Giuseppina Pisu, Mary Tresa Zanda, Liliana Contu, Elisabetta Maciocco, Mariangela Serra, Paolo Follesa
Summary: This study investigates the role of the GABA(B)R receptor in alcohol consumption and preference in mice. The results show that mice lacking functional GABA(B)R drink more alcohol, prefer alcohol over water, and have higher blood alcohol concentrations compared to wild-type mice. Additionally, the study suggests that the GABA(B)R receptor modulates the activity of GABA(A) receptors in the hippocampus, potentially influencing alcohol preference in mice.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Physiology
Elisabeth Rohbeck, Corinna Niersmann, Karl Koehrer, Thorsten Wachtmeister, Michael Roden, Juergen Eckel, Tania Romacho
Summary: This study investigated the effect of HK4 on lipotoxicity-induced hepatocyte injury at the transcriptional level. It was found that HK4 specifically targets mitochondrial respiration, protein ubiquitination, apoptosis and cell cycle, thereby counteracting lipotoxic mechanisms and potentially treating non-alcoholic fatty liver disease (NAFLD).
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Oncology
Xuetian Qian, Chengfei Jiang, Shanshan Shen, Xiaoping Zou
Summary: This study identified GPRC5A as the most valuable gene in predicting the survival of pancreatic cancer patients, with high expression associated with larger tumors, higher TNM stages, higher tumor grades, and more positive resection margins. Mechanistically, GPRC5A may promote metastasis of pancreatic cancer mainly through regulating EMT and neuroactive ligand-receptor interaction.
Article
Biochemistry & Molecular Biology
Spencer R. Pierce, Allison L. Germann, Sophia Q. Xu, Saumith L. Menon, Marcelo O. Ortells, Hugo R. Arias, Gustav Akk
Summary: In this study, mutational analysis was used to investigate the involvement and contributions of individual intersubunit interfaces to the modulation of the alpha 1 beta 2 gamma 2L GABA(A) receptor by NS-1738 and PAM-2. The results showed that mutations to any single interface can completely abolish the potentiation by the alpha 7-PAMs. The findings are discussed in terms of energetic additivity and interactions between the different binding sites.
Article
Biophysics
Jeevan B. Gc, Christopher T. Szlenk, Ayobami Diyaolu, Peter Obi, Haiyang Wei, Xutong Shi, K. Michael Gibson, Senthil Natesan, Jean -Baptiste Roullet
Summary: This study reveals that all-trans farnesol, an endogenous alcohol in the human brain, can modulate the activity of GABAARs, expanding its pharmacological activities to ion channels involved in neurotransmission, and providing new insights into the communication between GABA neurotransmission and the cholesterol synthesis pathway.
BIOPHYSICAL JOURNAL
(2023)
Article
Neurosciences
Nevin Varghese, Nicolas E. Amelinez-Robles, Barclay Morrison III
Summary: In this study, the effects of blast-induced traumatic brain injury (bTBI) on the hippocampal network of rat organotypic hippocampal slice cultures (OHSCs) were investigated. The results showed reduced connectivity and clustering coefficients in the hippocampal network following bTBI, along with decreased expression of alpha 1 and alpha 5 GABAA receptor subunits. Treatment with the histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) restored the alpha 1 subunit and attenuated deficits in network measures. These findings suggest that GABAA receptors may play a role in neuronal network changes and could be targeted for therapeutic intervention in bTBI-induced neurological symptoms.
EXPERIMENTAL NEUROLOGY
(2023)
Review
Medicine, General & Internal
Sophie Schweizer-Schubert, Jennifer L. Gordon, Tory A. Eisenlohr-Moul, Samantha Meltzer-Brody, Katja M. Schmalenberger, Radoslaw Slopien, Anna-Lena Zietlow, Ulrike Ehlert, Beate Ditzen
Summary: Women are more likely to suffer from depression than men, especially during the reproductive years. Reproductive mood disorders involve various physiological, genetic, neural, and psychological factors, with some women showing increased sensitivity to hormonal fluctuations. The role of psychosocial factors in reproductive mood disorders remains understudied.
FRONTIERS IN MEDICINE
(2021)
Review
Clinical Neurology
Min-Yu Sun, Andrew J. Linsenbardt, Christine M. Emnett, Lawrence N. Eisenman, Yukitoshi Izumi, Charles F. Zorumski, Steve Mennerick
Article
Neurosciences
Min-Yu Sun, Yukitoshi Izumi, Ann Benz, Charles F. Zorumski, Steven Mennerick
JOURNAL OF NEUROPHYSIOLOGY
(2016)
Article
Neurosciences
Min-Yu Sun, Mariangela Chisari, Lawrence N. Eisenman, Charles F. Zorumski, Steven J. Mennerick
JOURNAL OF NEUROPHYSIOLOGY
(2017)
Article
Neurosciences
Courtney Sobieski, Michael J. Fitzpatrick, Steven J. Mennerick
JOURNAL OF NEUROSCIENCE
(2017)
Article
Multidisciplinary Sciences
Courtney Sobieski, Natasha Warikoo, Hong-Jin Shu, Steven Mennerick
Article
Multidisciplinary Sciences
Min-Yu Sun, Amanda Taylor, Charles F. Zorumski, Steven Mennerick
Article
Neurosciences
Mariangela Chisari, Timothy J. Wilding, Samuel Brunwasser, Kathiresan Krishnan, Mingxing Qian, Ann Benz, James E. Huettner, Charles F. Zorumski, Douglas F. Covey, Steven Mennerick
Review
Endocrinology & Metabolism
Peter M. Lambert, Xinguo Lu, Charles F. Zorumski, Steven Mennerick
Summary: The rise of ketamine and brexanolone as rapid antidepressant treatments has prompted research into their common mechanisms. These drugs have distinct characteristics compared to traditional antidepressants in terms of onset time and duration of effect. Based on existing studies, network disinhibition and increased high-frequency oscillations are potential mechanisms underlying the acute effects of rapid antidepressants.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Neurosciences
Yukitoshi Izumi, Anil G. Cashikar, Kathiresan Krishnan, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski
Summary: Inflammatory cells synthesize and release the oxysterol 25-hydroxycholesterol (25HC), which has antiviral and immunomodulatory properties. Activation of innate immunity by lipopolysaccharide (LPS) affects 25HC production in microglia and influences CA1 hippocampal synaptic plasticity and learning. 25HC serves as a key modulator of synaptic plasticity and memory under proinflammatory stimuli.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Peter M. Lambert, Richard Ni, Ann Benz, Nicholas R. Rensing, Michael Wong, Charles F. Zorumski, Steven Mennerick
Summary: This study explored the EEG signatures of neurosteroid allopregnanolone and other GABA(A) positive modulators in mice, as well as their similarities and differences with ketamine. The results suggest that rapid antidepressants with different molecular substrates may remain separated at the level of large-scale ensemble activity, but could have commonalities in more discrete circuits and/or in the context of a dysfunctional brain.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Psychiatry
Yukitoshi Izumi, Angela M. Reiersen, Eric J. Lenze, Steven J. Mennerick, Charles F. Zorumski
Summary: By studying rat hippocampal slices, it was found that fluvoxamine and other selective serotonin reuptake inhibitors (SSRIs) can overcome the inhibition of long-term potentiation (LTP) caused by acute inflammatory stimulus, possibly through activation of Sigma 1 receptors (S1Rs) and synthesis of neurosteroids. These SSRIs may be beneficial in diseases involving inflammatory stress.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Xinguo Lu, Peter Lambert, Ann Benz, Charles F. Zorumski, Steven J. Mennerick
Summary: AlloP is a neurosteroid that enhances GABAA receptor inhibition and is used to treat postpartum depression. Its antidepressant mechanism involves selective action at GABAA receptors containing the d subunit. However, recent research suggests that hippocampal PV interneurons have low sensitivity to AlloP and are unlikely to contribute to the mood-altering effects of neurosteroids through GABA effects.
Review
Neurosciences
Jamie L. Maguire, Steven Mennerick
Summary: Neuroactive steroids are a new class of antidepressants that have a rapid and long-lasting effect, different from previous treatments and other compounds. They act by positive allosteric modulation of GABA(A) receptors, and may also target intracellular pathways. Further research is needed to understand their molecular mechanisms and effects on behavior.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Charles F. Zorumski, Steven M. Paul, Douglas F. Covey, Steven Mennerick
NEUROBIOLOGY OF STRESS
(2019)
Article
Pharmacology & Pharmacy
Sampurna Chakrabarti, Mingxing Qian, Kathiresan Krishnan, Douglas F. Covey, Steven Mennerick, Gustav Akk
MOLECULAR PHARMACOLOGY
(2016)