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Biomolecules
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Brain Sterols: Biosynthesis and Physiology in Health and Disease
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Brain Sterols: Biosynthesis and Physiology in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Synthetic Biology and Bioengineering".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 6375

Special Issue Editors

Prof. Dr. Karoly Mirnics

E-Mail Website
Guest Editor
Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA
Interests: transcriptome changes across human brain disorders; animal models of psychiatric disorders; effects of environment on gene expression; sterol biosynthesis; CNS side effects of medications
Prof. Dr. Zeljka Korade

E-Mail Website
Guest Editor
Department of Pediatrics, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
Interests: inborn errors of sterol metabolism; polypharmacy; autism; antipsychotics; neurodevelopmental disorders

Special Issue Information

Dear Colleagues,

The brain fully relies on its intrinsic sterol biosynthesis. Cholesterol in the nervous system is a critical structural component of cellular membranes and lipid rafts, required for synapse and dendrite formation and axonal guidance, and it serves as a precursor for various biosynthetic pathways. In this Special Issue, we explore brain sterol biosynthesis, turnover, function, distribution, and pathophysiological changes associated with inborn errors of sterol metabolism, development, aging, and neuropsychiatric disorders. We also explore medication effects on brain sterol biosynthesis through the lifespan. We welcome your reviews and original data articles on this very important research topic.

Prof. Dr. Karoly Mirnics 
Prof. Dr. Zeljka Korade
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sterol biosynthesis
  • sterol turnover
  • oxysterol
  • brain
  • cholesterol
  • development
  • aging
  • medication side effects
  • inborn errors of sterol biosynthesis
  • DHCR7

Published Papers (4 papers)

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Research

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22 pages, 4711 KiB  
Article
Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia
by Ena Španić Popovački, Dora Vogrinc, Heidi R. Fuller, Lea Langer Horvat, Davor Mayer, Janja Kopić, Klara Pintarić, Mirjana Babić Leko, Mihaela Pravica, Željka Krsnik, Darko Marčinko, Marina Šagud, Patrick R. Hof, Mihovil Mladinov and Goran Šimić
Biomolecules 2024, 14(3), 302; https://doi.org/10.3390/biom14030302 - 04 Mar 2024
Viewed by 1312
Abstract
Schizophrenia is a complex mental condition, with key symptoms marked for diagnosis including delusions, hallucinations, disorganized thinking, reduced emotional expression, and social dysfunction. In the context of major developmental hypotheses of schizophrenia, notably those concerning maternal immune activation and neuroinflammation, we studied NLRP1 [...] Read more.
Schizophrenia is a complex mental condition, with key symptoms marked for diagnosis including delusions, hallucinations, disorganized thinking, reduced emotional expression, and social dysfunction. In the context of major developmental hypotheses of schizophrenia, notably those concerning maternal immune activation and neuroinflammation, we studied NLRP1 expression and content in the postmortem brain tissue of 10 schizophrenia and 10 control subjects. In the medial orbitofrontal cortex (Brodmann’s area 11/12) and dorsolateral prefrontal cortex (area 46) from both hemispheres of six schizophrenia subjects, the NLRP1 mRNA expression was significantly higher than in six control brains (p < 0.05). As the expression difference was highest for the medial orbitofrontal cortex in the right hemisphere, we assessed NLRP1-immunoreactive pyramidal neurons in layers III, V, and VI in the medial orbitofrontal cortex in the right hemisphere of seven schizophrenia and five control brains. Compared to controls, we quantified a significantly higher number of NLRP1-positive pyramidal neurons in the schizophrenia brains (p < 0.01), suggesting NLRP1 inflammasome activation in schizophrenia subjects. Layer III pyramidal neuron dysfunction aligns with working memory deficits, while impairments of pyramidal neurons in layers V and VI likely disrupt predictive processing. We propose NLRP1 inflammasome as a potential biomarker and therapeutic target in schizophrenia. Full article
(This article belongs to the Special Issue Brain Sterols: Biosynthesis and Physiology in Health and Disease)
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15 pages, 2820 KiB  
Article
Chronic Aripiprazole and Trazodone Polypharmacy Effects on Systemic and Brain Cholesterol Biosynthesis
by Zeljka Korade, Allison Anderson, Marta Balog, Keri A. Tallman, Ned A. Porter and Karoly Mirnics
Biomolecules 2023, 13(9), 1321; https://doi.org/10.3390/biom13091321 - 28 Aug 2023
Cited by 1 | Viewed by 2348
Abstract
The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole (ARI), an antipsychotic, and trazodone (TRZ), an antidepressant. In addition to their effects on dopamine and serotonin systems, both [...] Read more.
The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole (ARI), an antipsychotic, and trazodone (TRZ), an antidepressant. In addition to their effects on dopamine and serotonin systems, both of these compounds are inhibitors of the 7-dehydrocholesterol reductase (DHCR7) enzyme. To evaluate the systemic and nervous system distribution of ARI and TRZ and their effects on cholesterol biosynthesis, adult mice were treated with both ARI and TRZ for 21 days. The parent drugs, their metabolites, and sterols were analyzed in the brain and various organs of mice using LC-MS/MS. The analyses revealed that ARI, TRZ, and their metabolites were readily detectable in the brain and organs, leading to changes in the sterol profile. The levels of medications, their metabolites, and sterols differed across tissues with notable sex differences. Female mice showed higher turnover of ARI and more cholesterol clearance in the brain, with several post-lanosterol intermediates significantly altered. In addition to interfering with sterol biosynthesis, ARI and TRZ exposure led to decreased ionized calcium-binding adaptor molecule 1 (IBA1) and increased DHCR7 protein expression in the cortex. Changes in sterol profile have been also identified in the spleen, liver, and serum, underscoring the systemic effect of ARI and TRZ on sterol biosynthesis. Long-term use of concurrent ARI and TRZ warrants further studies to fully evaluate the lasting consequences of altered sterol biosynthesis on the whole body. Full article
(This article belongs to the Special Issue Brain Sterols: Biosynthesis and Physiology in Health and Disease)
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Review

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26 pages, 854 KiB  
Review
Lipid Rafts: The Maestros of Normal Brain Development
by Barbara Viljetić, Senka Blažetić, Irena Labak, Vedrana Ivić, Milorad Zjalić, Marija Heffer and Marta Balog
Biomolecules 2024, 14(3), 362; https://doi.org/10.3390/biom14030362 - 18 Mar 2024
Viewed by 843
Abstract
Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation of functional neuronal networks. This review focuses on the multifaceted involvement of lipid rafts in key neurodevelopmental processes, including [...] Read more.
Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation of functional neuronal networks. This review focuses on the multifaceted involvement of lipid rafts in key neurodevelopmental processes, including neural differentiation, synaptogenesis and myelination. Through the spatial organisation of signalling components, lipid rafts facilitate precise signalling events that determine neural fate during embryonic development and in adulthood. The evolutionary conservation of lipid rafts underscores their fundamental importance for the structural and functional complexity of the nervous system in all species. Furthermore, there is increasing evidence that environmental factors can modulate the composition and function of lipid rafts and influence neurodevelopmental processes. Understanding the intricate interplay between lipid rafts and neurodevelopment not only sheds light on the fundamental mechanisms governing brain development but also has implications for therapeutic strategies aimed at cultivating neuronal networks and addressing neurodevelopmental disorders. Full article
(This article belongs to the Special Issue Brain Sterols: Biosynthesis and Physiology in Health and Disease)
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20 pages, 1144 KiB  
Review
Methodological Pitfalls of Investigating Lipid Rafts in the Brain: What Are We Still Missing?
by Kristina Mlinac-Jerkovic, Svjetlana Kalanj-Bognar, Marija Heffer and Senka Blažetić
Biomolecules 2024, 14(2), 156; https://doi.org/10.3390/biom14020156 - 28 Jan 2024
Cited by 1 | Viewed by 1393
Abstract
The purpose of this review is to succinctly examine the methodologies used in lipid raft research in the brain and to highlight the drawbacks of some investigative approaches. Lipid rafts are biochemically and biophysically different from the bulk membrane. A specific lipid environment [...] Read more.
The purpose of this review is to succinctly examine the methodologies used in lipid raft research in the brain and to highlight the drawbacks of some investigative approaches. Lipid rafts are biochemically and biophysically different from the bulk membrane. A specific lipid environment within membrane domains provides a harbor for distinct raftophilic proteins, all of which in concert create a specialized platform orchestrating various cellular processes. Studying lipid rafts has proved to be arduous due to their elusive nature, mobility, and constant dynamic reorganization to meet the cellular needs. Studying neuronal lipid rafts is particularly cumbersome due to the immensely complex regional molecular architecture of the central nervous system. Biochemical fractionation, performed with or without detergents, is still the most widely used method to isolate lipid rafts. However, the differences in solubilization when various detergents are used has exposed a dire need to find more reliable methods to study particular rafts. Biochemical methods need to be complemented with other approaches such as live-cell microscopy, imaging mass spectrometry, and the development of specific non-invasive fluorescent probes to obtain a more complete image of raft dynamics and to study the spatio-temporal expression of rafts in live cells. Full article
(This article belongs to the Special Issue Brain Sterols: Biosynthesis and Physiology in Health and Disease)
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