Neuroscience
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Excitability and axon/dendrite specification are the most distinctive features in the establishment of neuronal polarization. Conditioned medium from rat sciatic nerve (CM) induced a neuronal-like morphology in PC12 cells. Here we show that CM neuritogenic activity is limited to the induction of dendrites in PC12 cells. ⋯ These results suggested that the effect of CM might be mediated through pro-NGF. The difference between the results obtained with the generic inhibitor for Trk receptors and the specific inhibitors for TrkA and p75(NTR) receptors in CM-treated cells, suggested that alternative pathways could be used to regulate neurite elongation, axon specification and sodium currents in PC12 cells. These findings represent important clues to improve the understanding of the initiation of neuronal polarity.
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This study aimed to determine the potential of in vivo functional magnetic resonance imaging (fMRI) methods as a non-invasive means of detecting effects of increased 5-HT release in brain. Changes in blood-oxygenation level-dependent (BOLD) contrast induced by administration of the 5-HT-releasing agent, fenfluramine, were measured in selected brain regions of halothane-anesthetized rats. Initial immunohistochemical measurements of the marker of neural activation, Fos, confirmed that in halothane-anesthetized rats fenfluramine (10 mg/kg i.v.) evoked cellular responses in cortical regions which were attenuated by pre-treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (300 mg/kg i.p. once daily for 2 days). ⋯ Pre-treatment with p-chlorophenylalanine, significantly attenuated the response to fenfluramine (10 mg/kg i.v.) in all regions with the exception of the motor cortex which showed a trend. These experiments demonstrate that increased 5-HT release evokes region-specific changes in the BOLD signal in rats, and that this effect is attenuated in almost all regions by 5-HT depletion. These findings support the use of fMRI imaging methods as a non-invasive tool to study 5-HT function in animal models, with the potential for extension to clinical studies.
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Bath application of 5-HT (1-1000 muM) induced a tetrodotoxin (TTX)-resistant outward current at the holding membrane potential (V(H)) of -50 mV in 104/162 (64.2%) of substantia gelatinosa (SG) neurons from the rat spinal cord in vitro. The 5-HT-induced outward current was suppressed by an external solution containing Ba(2+), or a pipette solution containing Cs(2)SO(4) and tetraethylammonium. It was reversed near the equilibrium potential of the K(+) channel. ⋯ Furthermore, frequency, but not amplitude, of miniature IPSCs increased with perfusion with 5-HT in the presence of TTX. These findings, taken together, suggest that 5-HT induces outward currents through 5-HT(1A) receptors in excitatory SG neurons. These findings also suggest that the inward currents are post- and presynaptically evoked through 5-HT(3) receptors, probably in inhibitory neurons.
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High doses of salicylate, the anti-inflammatory component of aspirin, induce transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of salicylate, a dose that reliably induces tinnitus in rats, significantly reduced the sound evoked output of the rat cochlea. Paradoxically, salicylate significantly increased the amplitude of the sound-evoked field potential from the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC). ⋯ Salicylate significantly increased the amplitude of the startle response. Collectively, these results suggest that high doses of salicylate increase the gain of the central auditory system, presumably by down-regulating GABA-mediated inhibition, leading to an exaggerated acoustic startle response. The enhanced startle response may be the behavioral correlate of hyperacusis that often accompanies tinnitus and hearing loss.
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Sustained intracellular Ca(2+) elevation is a well-established contributor to neuronal injury following excessive activation of N-methyl-d-aspartic acid (NMDA)-type glutamate receptors. Zn(2+) can also be involved in excitotoxic degeneration, but the relative contributions of these two cations to the initiation and progression of excitotoxic injury is not yet known. We previously concluded that extended NMDA exposure led to sustained Ca(2+) increases that originated in apical dendrites of CA1 neurons and then propagated slowly throughout neurons and caused rapid necrotic injury. ⋯ Removal of extracellular Ca(2+) reduced, but did not prevent FluoZin-3 increases. These results suggest that sustained Ca(2+) increases indeed underlie Fura-6F signals that slowly propagate throughout neurons, and that Ca(2+) (rather than Zn(2+)) increases are ultimately responsible for neuronal injury during NMDA. However, mobilization of Zn(2+) from endogenous sources leads to significant neuronal Zn(2+) increases, that in turn contribute to mechanisms of initiation and progression of progressive Ca(2+) deregulation.