Changes in cholesterol concentration in the plasma membrane of presynaptic nerve terminals nonspecifically modulate glutamate transport and homeostasis in the central nervous system. Reduction of the cholesterol content in isolated rat brain nerve terminals (synaptosomes) using cholesterol-depleting agents decreases the glutamate uptake and increases the extracellular level of glutamate in nerve terminals. Extraction of cholesterol from the plasma membrane and its further removal from the synaptosomes by external magnetic field can be achieved by means of magnetic nanoparticles with immobilized cholesterol-depleting agent such as O-methyl-β-cyclodextrin (MCD). A simple approach is developed for preparation of maghemite (γ-FeO) nanoparticles containing chemically bonded MCD. The method is based on preparation of a silanization agent containing MCD. It is synthesized by the reaction of triethoxy(3-isocyanatopropyl)silane with MCD. Base-catalyzed silanization of superparamagnetic γ-FeO provides a relatively stable colloid product containing 48μmol of MCDg. MCD-modified γ-FeO nanoparticles decrease the initial rate of the uptake and accumulation of l-[C]glutamate and increase the extracellular l-[C]glutamate level in the preparation of nerve terminals. The effect of MCD-immobilized nanoparticles is the same as that of MCD solution; moreover, magnetic manipulation of the nanoparticles enables removal of bonded cholesterol.
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http://dx.doi.org/10.1016/j.colsurfb.2016.10.007 | DOI Listing |
Neurobiol Pain
December 2024
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Painful diabetic neuropathy (PDN) is a challenging complication of diabetes with patients experiencing a painful and burning sensation in their extremities. Existing treatments provide limited relief without addressing the underlying mechanisms of the disease. PDN involves the gradual degeneration of nerve fibers in the skin.
View Article and Find Full Text PDFEur J Neurosci
January 2025
Department of Pharmacology, University of Oxford, Oxford, UK.
Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Complexins are a family of small presynaptic proteins that regulate neurotransmitter release at nerve terminals and are highly conserved in evolution. While direct interactions with SNARE proteins are critical for all complexin functions, binding of their disordered C-terminal domains (CTD) to membranes, especially to synaptic vesicle membranes, is essential for the ability of complexin to inhibit vesicle release. Furthermore, while some complexin CTDs possess an endogenous affinity for membranes, other complexin isoforms are subject to lipidation at their C-termini, which is presumed to confer additional membrane binding.
View Article and Find Full Text PDFCureus
December 2024
Department of Periodontology and Implantology, Government Dental College and Hospital, Jamnagar, Jamnagar, IND.
Introduction In their routine practice, dentists frequently encounter dentinal hypersensitivity, which is caused by the pulpal nerves' increased excitability due to fluid movement in the dentinal tubules. It is treated in-office using dentin desensitizers, which reduce hypersensitivity by obstructing the open tubules or desensitizing the free nerve endings present within the tubules. However, no substance or treatment plan has ever been proven to be the gold standard for the efficient treatment of dentinal hypersensitivity.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Anesthesiology & Perioperative Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Aging disrupts multiple homeostatic processes, including autophagy, a cellular process for the recycling and degradation of defective cytoplasmic structures. Acute treatment with the autophagy inhibitor chloroquine blunts the maximal forces generated by the diaphragm muscle, but the mechanisms underlying neuromuscular dysfunction in old age remain poorly understood. We hypothesized that chloroquine treatment increases the presynaptic retention of the styryl dye FM 4-64 following high-frequency nerve stimulation, consistent with the accumulation of unprocessed bulk endosomes.
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