Studies have demonstrated alterations in brain membrane phospholipid metabolite levels in Alzheimer's disease (AD). The changes in phospholipid metabolite levels correlate with neuropathological hallmarks of the disease and measures of cognitive decline. This 31P nuclear magnetic resonance (NMR) study of Folch extracts of autopsy material reveals significant reductions in AD brain levels of phosphatidylethanolamine (PtdEtn) and phosphatidylinositol (PtdIns), and elevations in sphingomyelin (SPH) and the plasmalogen derivative of PtdEtn. In the superior temporal gyrus, there were additional reductions in the levels of diphosphatidylglycerol (DPG) and phosphatidic acid (PtdA). The findings are present in 3/3 as well as 3/4 and 4/4 apolipoprotein E (apoE) genotypes. The AD findings do not appear to reflect non-specific neurodegeneration or the presence of gliosis. The present findings could possibly contribute to an abnormal membrane repair in AD brains which ultimately results in synaptic loss and the aggregation of A beta peptide.
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http://dx.doi.org/10.1023/a:1011603916962 | DOI Listing |
Transl Psychiatry
January 2025
Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea.
Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests.
View Article and Find Full Text PDFProg Neurobiol
January 2025
Department of Biomedicine, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address:
The brain faces the challenging task of preserving a consistent portrayal of the external world in the face of disruptive sensory inputs. What alterations occur in sensory representation amidst noise, and how does brain activity adapt to it? Although it has previously been shown that background white noise (WN) decreases responses to salient sounds, a mechanistic understanding of the brain processes responsible for such changes is lacking. We investigated the effect of background WN on neuronal spiking activity, membrane potential, and network oscillations in the mouse central auditory system.
View Article and Find Full Text PDFLancet Neurol
January 2025
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. Electronic address:
The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.
View Article and Find Full Text PDFDev Cell
January 2025
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.
View Article and Find Full Text PDFJ Psychiatr Res
January 2025
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379, Oslo, Norway; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway; Department for Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway.
Biomarkers for the diagnosis and clinical management of psychiatric disorders are currently lacking. Extracellular vesicles (EVs), lipid membrane-encapsulated vesicles released by cells, hold promise as a source of biomarkers due to their ability to carry molecules that reflect the status of their donor cells and their ubiquitous presence in biofluids. This review examines the literature on EVs in biofluids from psychiatric disorder patients, and discuss how the published studies contribute to our understanding of the pathophysiology of these conditions and to the discovery of potential biomarkers.
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