Brain research
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To determine the normal mean reference normal value for metabolic ratios in the pons of healthy adult Chinese subjects by using proton magnetic resonance spectroscopy (1HMRS). ⋯ The ratios of NAA/Cr, NAA/Cho or Cho/Cr in the pons did not correlate with the age or gender of healthy subjects.
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The actions of neurotransmitter glycine are regulated by the Na+/Cl(-) dependent high-affinity glycine transporters, GlyT1 and GlyT2. These two members of the SLC6 transport family have been cloned and extensively characterized, however relatively little is known regarding their modulation. In the present study, glycine uptake in primary cultures of rat embryonic cortex has been characterized and the effects of the phosphatidylinositol 3 (PI3) kinase inhibitors LY 294002 and wortmannin on GlyT1- and GlyT2-mediated glycine uptake were investigated. ⋯ Kinetic analysis in the presence of LY 294002 demonstrated significant decreases of both Km and Vmax values, suggesting a mechanism of uncompetitive inhibition on GlyT1-mediated glycine uptake. In addition, glycine release was blocked by LY 294002. These results raised a possibility that LY 294002 might interact with GlyT1.
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The mechanisms by which agonists and other ligands bind ligand-gated ion channels are important determinants of function in neurotransmitter receptors. The partial agonist, kainic acid (KA) activates a less desensitized, and more robust AMPA receptor (AMPAR) current than full agonists, glutamate or AMPA. Cyclothiazide (CTZ), the allosteric modulator of AMPARs, potentiates receptor currents by inhibiting receptor desensitization resulting from agonist activation. ⋯ The potency of glutamate and KA activation of GluR1A782N was not significantly different from that of the wild-type GluR1 receptor although the mutant receptor currents were more sensitive to CTZ potentiation than the wild-type receptor current. This result is an indication that glutamate and KA binding to the agonist (S1/S2) domain on AMPAR can be modulated by an expendable splice-variable region of the receptor. Moreover, the effect of the allosteric modulator, CTZ on agonist activation of AMPAR can also be modified by a non-conserved amino acid residue substitution within the splice-variable "flip/flop" region.
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Neuronal differentiation and neurite outgrowth are key processes during development of the nervous system. Understanding the regulation of neurite outgrowth stimulated by neurotrophins is crucial to developing therapies to promote axon regeneration after injury or in neurodegenerative diseases. Treatment of PC12 cells with nerve growth factor (NGF) stimulates them to extend neurites and differentiate into a sympathetic neuron-like phenotype. ⋯ Inhibition of p38 MAPK signalling with SB202190 blocked phosphorylation of Hsp25 without affecting NGF-induced neurite outgrowth or the heat shock-dependent enhancement of elongation. These findings indicate that Hsp25 is not required for NGF-induced neurite outgrowth in PC12 cells and is not responsible for the heat shock-enhancement of NGF-induced neurite elongation. Instead, inhibition of MEK1/2 with U0126 partially reduced the heat shock-enhancement of NGF-stimulated neurite elongation.
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Recent studies have shown a close correspondence between perceptual detection thresholds for sounds in quiet and a measure of neuronal thresholds derived from the stimulus-dependent timing of the first spike of auditory-nerve fibers. In addition, stimulus properties might be encoded by differences in first-spike timing of neurons in the central auditory system. ⋯ Two of the 5 parameters can be considered constant (at least for the vast majority of fibers), while the other 3 vary in meaningful ways with the fibers' spontaneous discharge rates. The elements of the model and some implications are discussed.