Review
Neurosciences
Sara Carlini, Lauren M. Osborne, Kristina M. Deligiannidis
Summary: Postpartum depression has negative effects on childbearing persons globally. Current treatments have limited evidence, while hormonal treatments have rationality but limited efficacy. In contrast, the development of antidepressants with allopregnanolone analogues has shown promise.
DIALOGUES IN CLINICAL NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Eva Dolejsi, Nikolai Chetverikov, Eszter Szanti-Pinter, Dominik Nelic, Alena Randakova, Vladimir Dolezal, Esam E. El-Fakahany, Eva Kudova, Jan Jakubik
Summary: Endogenous neurosteroids and their synthetic analogues, known as neuroactive steroids, bind to muscarinic acetylcholine receptors and modulate acetylcholine binding and function. Radioligand binding experiments show that neuroactive steroids bind to two different affinity sites on the receptors, with each site having a unique binding profile compared to other allosteric modulators. Additionally, membrane cholesterol competes with neurosteroids/neuroactive steroids binding, indicating that both binding sites are oriented towards the cell membrane.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Michal Kaleta, Jana Oklestkova, Ondrej Novak, Miroslav Strnad
Summary: Neuroactive steroids are a family of compounds that can affect nervous system functions, synthesized in either the nervous system or peripheral endocrine tissues. Monitoring the production and levels of neuroactive steroids can be beneficial for the prevention, diagnosis, monitoring, and treatment of neurodegenerative and psychiatric diseases. Immunoanalytical methods and chromatography combined with mass spectrometry are highlighted as relevant techniques for analyzing neuroactive steroids.
Article
Immunology
Shibani S. Mukerji, Vikas Misra, David R. Lorenz, Sukrutha Chettimada, Kiana Keller, Scott Letendre, Ronald J. Ellis, Susan Morgello, Robert A. Parker, Dana Gabuzda
Summary: This study found that in HIV-infected individuals receiving ART, depressive symptoms were associated with lower levels of neuroactive steroids, suggesting altered neuroactive steroid metabolism may contribute to the pathophysiological mechanisms of depression.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Medicine, Research & Experimental
Thiraphat Saengmearnuparp, Bannakij Lojanapiwat, Nipon Chattipakorn, Siriporn Chattipakorn
Summary: Recent literature has linked 5-alpha reductase inhibitors (5-ARIs) with neuropsychiatric adverse effects, with former users showing a higher incidence of depressive symptoms. The mechanisms behind this association, known as post finasteride syndrome (PFS), are not yet fully understood. Possible mechanisms include alterations in neuroactive steroids, dopaminergic dysfunction, reduced hippocampal neurogenesis, increased neuroinflammation, alterations in the HPA axis, and epigenetic modifications.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Endocrinology & Metabolism
Jordan C. Barone, Elizabeth Wenzel, Viraja Alluri, Daniel Moriarity, Graziano Pinna, Erin Walsh, David R. Rubinow, Leslie Morrow, Tory A. Eisenlohr-Moul
Summary: This study examined the impact of the menstrual cycle and experimental manipulation on GABAergic neuroactive steroids (NAS) and peripheral cytokines. The results showed that progesterone-derived NAS increased in parallel with progesterone and with the administration of exogenous progesterone and estradiol during the perimenstrual period. Conversely, androstane NAS either did not fluctuate or fluctuated inversely from progesterone and decreased with exogenous hormone administration. Peripheral cytokines did not show cyclical patterns, but were significant predictors of suicidal ideation, depressed mood, and anxiety. Concomitant use of SSRI medication predicted lower androstane NAS.
PSYCHONEUROENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ewa Szczurowska, Eszter Szanti-Pinter, Alena Randakova, Jan Jakubik, Eva Kudova
Summary: Muscarinic acetylcholine receptors are membrane receptors involved in various physiological processes, and dysfunction of their signaling is associated with internal diseases and psychiatric/neurologic conditions. Steroidal compounds, besides their genomic effects, can also modulate membrane proteins including muscarinic acetylcholine receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Pantelis Antonoudiou, Phillip L. W. Colmers, Najah L. Walton, Grant L. Weiss, Anne C. Smith, David P. Nguyen, Mike Lewis, Michael C. Quirk, Lea Barros, Laverne C. Melon, Jamie L. Maguire
Summary: The study demonstrates that allopregnanolone and its neuroactive steroid analogs modulate network states in different species, with a key role in the basolateral amygdala. These steroids alter behavioral states by influencing oscillatory activities, protecting mice from chronic stress-induced disruptions in network and behavioral states.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Gastroenterology & Hepatology
Sik Yu So, Tor C. Savidge
Summary: This review focuses on how neuroactive steroids modulate enteric nervous system function by influencing receptors in the intestine. The potential role of the gut microbiota in modulating neuroactive steroid signaling along the gut-brain axis is also highlighted.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Cell Biology
Haisheng Zhao, Xijing Mao, Cuilin Zhu, Xiaohan Zou, Fanzhen Peng, Wei Yang, Bingjin Li, Guangquan Li, Tongtong Ge, Ranji Cui
Summary: Autism spectrum disorder (ASD) is a series of neurodevelopmental diseases characterized by social communication deficits and repetitive behaviors. The dysregulation of GABAergic synaptic transmission is implicated in the pathogenesis of ASD, although the specific molecular mechanism is still unclear.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Endocrinology & Metabolism
Silvia Diviccaro, Lucia Cioffi, Eva Falvo, Silvia Giatti, Roberto Cosimo Melcangi
Summary: The review discusses the synthesis of allopregnanolone in the nervous system, its physiological and neuroprotective effects, as well as its sex-dimorphic nature. Allopregnanolone's low bioavailability and extensive hepatic metabolism limit its use as a drug, leading to proposals for synthetic analogues or alternative therapeutic strategies to increase its levels.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Elizabeth S. Wenzel, Graziano Pinna, Tory Eisenlohr-Moul, Beatriz Penalver Bernabe, Raquel Romay Tallon, Unnathi Nagelli, John Davis, Pauline M. Maki
Summary: The study suggests a dynamic relationship between NAS and perinatal depression (PND), with different metabolic levels of NAS potentially contributing to depression at various stages of pregnancy. While low ALLO levels have been associated with postpartum depression, a higher metabolism of P4 to ALLO (resulting in higher ALLO levels) earlier in pregnancy is linked to depression. Some women may exhibit a hormone-sensitive depressive response to acute increases in NAS metabolism in early pregnancy.
PSYCHONEUROENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Verica Milivojevic, Lily Charron, Nia Fogelman, Gretchen Hermes, Rajita Sinha
Summary: Chronic cocaine use leads to adaptations in stress biology and the neuroactive steroid system. The study found that pregnenolone, a precursor to neuroactive steroids, decreases cocaine craving and anxiety, as well as reduces stress-induced autonomic arousal in individuals with cocaine use disorder.
Review
Biochemistry & Molecular Biology
Alexei Verkhratsky, Arthur Butt, Baoman Li, Peter Illes, Robert Zorec, Alexey Semyanov, Yong Tang, Michael V. Sofroniew
Summary: This article introduces the pathophysiology of astroglial cells in neurological diseases and disorders, discussing their changes and functions in different pathological states, and proposes the identification of cellular and molecular mechanisms of astroglial pathophysiology as a new frontier for finding novel therapeutic strategies.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Nemanja Useinovic, Stefan Maksimovic, Michelle Near, Nidia Quillinan, Vesna Jevtovic-Todorovic
Summary: Since its invention, general anesthesia has been crucial in modern surgery. However, concerns about the negative effects of anesthetics on the developing brain have been raised through preclinical studies and clinical evidence. Further understanding the molecular basis of anesthesia-induced neurotoxicity is important for developing protective strategies and ensuring safe usage during critical stages of brain development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)