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Two discoveries have put D-serine in the spotlight of neuroscience. First, D-serine was detected in brain tissue at high levels. Second, it was found to act on the N-methyl-D-aspartate receptor (NMDAR). This receptor is central to use-dependent synaptic plasticity, the cellular process which is widely believed to underlie learning. The ensuing quest for the mechanisms of D-serine synthesis, release and clearance, as well as for its physiological significance has provided a wealth of experimental evidence implicating D-serine in synaptic plasticity. However some key questions remain unanswered. Which cells release D-serine and upon what stimuli? Is D-serine supply dynamically regulated? What is the fate of released D-serine? Answering these questions appears to be an essential step in our understanding of how NMDARs trigger synaptic plasticity and learning. This review will highlight some recent advances and avenues of enquiry in dynamic D-serine signaling in the mammalian brain with emphasis on neurophysiology.
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http://dx.doi.org/10.1016/j.biocel.2012.01.005 | DOI Listing |
Life Sci
March 2025
Department of Chinese Medicine, Shandong Mental Health Center, Shandong University, Jinan, China. Electronic address:
Exosomes are a class of extracellular vesicles that encompass a diverse array of bioactive molecules, including proteins, lipids, mRNA, and microRNA(miRNA). Virtually all cell types release exosomes under both physiological and pathological conditions. In addition to electrical and chemical signals, exosomes are an alternative route of signaling between cells in the brain.
View Article and Find Full Text PDFNeuron
March 2025
Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA; Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO 63110, USA. Electronic address:
Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164 (57%) are novel.
View Article and Find Full Text PDFSTAR Protoc
March 2025
Section on Synapse Development Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
The temporoammonic pathway (TAP), the direct input from the entorhinal cortex to the hippocampus, is an important model structure for investigating synaptic plasticity. Here, we present a protocol for preparing TAP containing ex vivo slices from mice and conducting extracellular recordings of TAP inputs. We describe the specific slicing plane, an angled horizontal slice preparation, along with anatomical hallmarks for the identification of stimulation and recording electrode placement.
View Article and Find Full Text PDFInflammopharmacology
March 2025
Department of Pharmacology, Laureate Institute of Pharmacy Kathog, Kangra, 177101, India.
Alzheimer's disease, a neurodegenerative disorder, is characterized by cognitive impairment, neuronal loss, and synaptic dysfunction. The interplay between the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the caspase-mediated apoptotic cascade plays a pivotal role in its progression. The signaling pathway responsible for neuronal survival also regulates synaptic plasticity and resistance to oxidative stress, whereas caspase activation accelerates neurodegeneration by triggering cell death and inflammation.
View Article and Find Full Text PDFJ Neurosci
March 2025
Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
The endoplasmic reticulum (ER) is the largest intracellular Ca store, serving as the source and sink of intracellular Ca The ER Ca store is continuous yet organized into distinct subcompartments with spatial and functional heterogeneity. In cerebellar Purkinje cells (PCs), glutamatergic inputs trigger Ca release from specific ER domains via inositol 1,4,5-trisphosphate receptors (IPRs) or ryanodine receptors (RyRs). Upon ER store depletion, refilling occurs through store-operated Ca entry mediated by stromal interaction molecule-1 (STIM1).
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