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There is growing evidence that lithium used in the treatment of bipolar disorder (BD) affects molecular targets that are involved in neuronal growth, survival, and maturation, but it remains unclear if neuronal alterations in any of these molecules predict specific symptom changes in BD patients undergoing lithium monotherapy. The goals of this study were to (a) determine which molecular changes in the olfactory neurons of symptomatic patients receiving lithium are associated with antimanic or antidepressant response, and (b) uncover novel intraneuronal regulatory mechanisms of lithium therapy. Twenty-two treatment-naïve non-smoking patients, with symptomatic BD underwent nasal biopsies for collection of olfactory tissues, prior to their treatment and following a 6-week course of lithium monotherapy. Sixteen healthy controls were also biopsied. Combining laser capture microdissection with real-time polymerase chain reaction, we investigated baseline and treatment-associated transcriptional changes in candidate molecular targets of lithium action in the olfactory neuroepithelium. Baseline mRNA levels of glycogen synthase kinase 3 beta (GSK3β) and collapsin response mediator protein 1 (CRMP1) genes were significantly associated with BD status and with severity of mood symptoms. Among BD subjects, treatment-associated downregulation of CRMP1 expression was most predictive of decreases in both manic and depressive symptoms. This study provides a novel insight into the relevance of CRMP1, a key molecule in semaphorin-3A signaling during neurodevelopment, in the molecular mechanism of action of lithium, and in the pathophysiology of BD. It supports the use of human-derived olfactory neuronal tissues in the evaluation of treatment response of psychiatric disorders.
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http://dx.doi.org/10.1038/s41398-018-0126-6 | DOI Listing |
Biol Psychiatry Glob Open Sci
January 2025
Department of Psychiatry, New York University Grossman School of Medicine, New York, New York.
Background: An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.
Methods: We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels.
Ann Neurol
December 2024
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.
Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis.
Elife
December 2024
Sorbonne Université, Centre National de la Recherche Scientifique (CNRS UMR7622), Institut de Biologie Paris-Seine (IBPS), Developmental Biology Laboratory, Paris, France.
Despite recent progress, the complex roles played by the extracellular matrix in development and disease are still far from being fully understood. Here, we took advantage of the zebrafish mutation which affects Laminin γ1, a major component of basement membranes, to explore its role in the development of the olfactory system. Following a detailed characterisation of Laminin distribution in the developing olfactory circuit, we analysed basement membrane integrity, olfactory placode and brain morphogenesis, and olfactory axon development in mutants, using a combination of immunochemistry, electron microscopy and quantitative live imaging of cell movements and axon behaviours.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address:
Odorant binding proteins (OBPs) play key roles in the insect olfactory system by assisting the neuronal response to hydrophobic odor molecules, understanding their interaction with ligands will facilitate the virtual screening of behaviorally active compounds in insects. Here, we successfully cloned and confirmed CmedOBP13, an antennae-biased OBP from the rice leaffolder Cnaphalocrocis medinalis, as a secreted protein. Recombinant CmedOBP13 was obtained using the Escherichia coli system, and its binding affinities to 35 volatile compounds emitted by rice plants and three sex pheromone components from female moths were assessed by a competitive binding assay.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, China; Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China; Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, China. Electronic address:
In recent years, there has been a notable increase in the concentration of air pollutants in the troposphere, especially ozone. However, limited research has gone beyond examining histopathological alterations in the olfactory bulb (OB) to explore the effects of ozone exposure on olfactory and cognitive functions. In our study, we exposed nine-month-old C57BL/6 mice to ozone at a concentration of 1.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!