Neuroscience
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We monitored survival of Purkinje cells in rat cerebellar slices to test the hypothesis that isoflurane preconditioning reduces ischemia-induced neuronal death. Preconditioning the brain slices with isoflurane, a volatile anesthetic commonly used in clinical practice, at 1-4% for 15 min at 37 degrees C significantly decreased Purkinje cell injury and death caused by a 20-min ischemia (simulated by oxygen-glucose deprivation, OGD). The effective concentration for half of the maximal effect (EC(50)) for this isoflurane preconditioning-induced neuroprotection was 1.17+/-0.31% and the maximal protective effects were achieved at 3% or higher concentrations of isoflurane. ⋯ Our results suggest that isoflurane preconditioning is neuroprotective. The isoflurane concentrations and times needed for the preconditioning to be neuroprotective are clinically relevant. The mechanisms of this protection seem to involve modulation of glutamate transporter activity.
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The expression and functional responses of P2X receptors in bladder and cutaneous sensory neurons of adult rats and mice have been studied using immunohistochemistry and patch clamp techniques. Cell bodies of bladder pelvic afferents were identified in L6 and S1 dorsal root ganglia (DRG), following Fast Blue injection into the muscle wall of the urinary bladder. Similarly, cutaneous sensory neurons were identified in L3 and L4 DRG, following Fast Blue injection into the saphenous nerve innervating the skin. ⋯ The remaining bladder sensory neurons demonstrated biphasic, transient or no response to P2X agonists. In contrast, only 24% of cutaneous afferent neurons gave persistent currents to alpha beta meATP (30 microM), with 66% of cells giving transient or biphasic currents and the remaining 10% being non-responsive. Our results suggest that, in contrast to DRG neurons in general, bladder sensory neurons projecting via pelvic nerves express predominantly P2X(2/3) heteromeric receptors, which are likely to mediate the important roles of ATP as a signaling molecule of urinary bladder filling and nociception.
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Disruption of the glucocorticoid negative feedback system is observed in approximate one half of human depressives, and a similar condition is induced in animals by chronic stress. This disruption is thought to involve down-regulation of glucocorticoid receptors (GRs) in the feedback sites of the brain. However, the responsible site of the brain has not been well elucidated. ⋯ In addition, when DEX was injected systemically to the chronically stressed rats, the suppressive response to DEX was significantly attenuated. These results suggest that the abnormal changes in GRs in the higher centers of the hypothalamo-pituitary-adrenal axis are involved in the chronic stress-induced attenuation of the feedback. Since dysfunction of the PFC or hippocampus is implicated in the pathogenesis of depression, the present findings would help to understand the mechanisms underlying the disrupted feedback system and its relation to brain dysfunction in depression.
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The main neuronal population of the striatum is composed of the medium spiny neurones (MSNs). In fact several sub-populations of MSNs can be distinguished according to the striatal compartment (striosomes and matrix) to which they belong, their afferents and their sites of projection, their biochemical markers and their morphologies. However, these cells are generally described as an electrophysiological homogeneous population. ⋯ Micro-domains differing by their magnitude of adaptation could be distinguished within the spike frequency adaptation process. A subgroup of MSNs exists, showing a marked spike frequency adaptation together with other distinct properties, such as shorter delay to first spike and membrane time constant, and higher initial frequency and action potential threshold. In conclusion, when strong cortical inputs are delivered in coincidence, adapting MSNs could not only transmit faster the first AP but also exert a sort of cutoff of the transmission due to their spike frequency adaptation process.
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Following the hypothesis of the "signal-to-noise" ratio we examined whether changes in the activity of group-I metabotropic glutamate (mGlu) receptors in the hippocampus are associated with a condition that specifically enhances the learning capacity in rats. As a model, we used rats that had been nursed by mothers drinking a solution of corticosterone (13.5 mg of daily intake of corticosterone hemisuccinate) during the lactation period. These rats were prone to learn, as indicated by a better performance in a passive avoidance test. ⋯ Western blot analysis showed a selective reduction in the expression of mGlu1a receptor protein in the hippocampus of corticosterone-nursed rats, whereas expression of mGlu5 and mGlu2/3 receptors was unchanged. The reduction in mGlu-receptor mediated PI hydrolysis in the hippocampus may contribute to the greater learning capacity of corticosterone-nursed rats by reducing the background noise over which a specific signal must be superimposed during learning. This hypothesis was supported by the evidence that mGlu-receptor stimulated PI hydrolysis was amplified in hippocampal slices from rats subjected to a passive avoidance learning paradigm, and that this amplification was greater in slices from corticosterone-nursed rats of both sexes.