Neuroscience
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Angiotensins (Angs) modulate blood pressure, hydro-electrolyte composition, and antinociception. Although Ang (5-8) has generally been considered to be inactive, we show here that Ang (5-8) was the smallest Ang to elicit dose-dependent responses and receptor-mediated antinociception in the rat ventrolateral periaqueductal gray matter (vlPAG). Ang (5-8) antinociception seems to be selective, because it did not alter blood pressure or act on vascular or intestinal smooth muscle cells. ⋯ Endopeptidase EP 24.11 and amastatin-sensitive aminopeptidase from the vlPAG catalyzed the synthesis (from Ang II or Ang III) and inactivation of Ang (5-8), respectively. Selective inhibitors of neuronal-nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and a non-selective opioid receptor (opioid-R) inhibitor blocked Ang (5-8)-induced antinociception. In conclusion, Ang (5-8) is a new member of the Ang family that selectively and strongly modulates antinociception via NO-sGC and endogenous opioid in the vlPAG.
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In this study, we assessed the effects of varying tetanus and test-pulse intensity on the magnitude of long-term potentiation (LTP) in the perforant path-dentate gyrus projection of urethane-anaesthetized rats. We developed a novel within-subjects procedure in which test-pulse-stimulation intensity (60-1000 μA) was varied quasi-randomly under computer control throughout the recording period. After a baseline period, we applied a high-frequency tetanus, the intensity of which was varied over the same range as test-pulse intensity, but between subjects. ⋯ After 1000-μA tetanization of the original ('upstream') site, fEPSPs were again depressed in response to test stimulation of the upstream site, but only potentiation was observed in response to stimulation of the downstream site. This is consistent with the idea that the depression induced by intense tetanization results from local changes at the stimulation site. In conclusion, while tetanus intensity must exceed the LTP induction threshold, intensities above 500 μA should be avoided; in the present study, tetanization at 250-500 μA yielded maximal levels of LTP.
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This review aims to characterize fatigue-related changes in corticospinal excitability and inhibition in healthy subjects. Transcranial magnetic stimulation (TMS) has been extensively used in recent years to investigate modifications within the brain during and after fatiguing exercise. Single-pulse TMS reveals reduction in motor-evoked potentials (MEP) when measured in relaxed muscle following sustained fatiguing contractions. ⋯ This review examines the mechanical and EMG responses elicited by TMS (single- and paired-pulse) and cervicomedullary stimulation both during and after a fatiguing exercise. Particular attention is given to the muscle state and the type of fatiguing exercise when assessing and interpreting fatigue-induced changes in these parameters. Methodological concerns and future research interests are also considered.
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Involvement of Nrf2 signaling pathway in the neuroprotective activity of natural kaurane diterpenes.
Oxidative stress is a common harmful condition of several neurodegenerative diseases. Antioxidants represent the medical choice strategy for protection against this unbalanced oxidant-antioxidant status. The present study was undertaken to address the role of kaurane diterpenes foliol, linearol and sidol in the protection against H(2)O(2)-induced oxidative stress in the human astrocytoma U373-MG cell line and to establish the underlying mechanisms. ⋯ Furthermore, these natural products increased Nrf2 nuclear levels, suggesting the activation of this master regulator of antioxidative gene expressions in the protective effect exhibited by the kaurane diterpenes studied. Collectively, these results suggest that the studied kaurane diterpenes, mainly linearol and sidol, protect U373-MG cells from H(2)O(2)-induced injury or degeneration presumably by antioxidant mechanisms. These compounds may be useful agents for counteracting the oxidative damage occurring during the pathological development of several CNS disorders.
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In adult mammals, newborn neural precursor cells (NPCs) derived from either the subventricular zone (SVZ) or the subgranular zone (SGZ) migrate into the olfactory bulb and the dentate gyrus (DG), respectively, where some of them mature into excitatory and inhibitory neurons. There is increasing evidence that this neurogenesis process is important for some types of learning and synaptic plasticity and vice versa. Survivin, a member of the inhibitor-of-apoptosis protein (IAP) family, has been suggested to have a central role in the regulation of neurogenesis. ⋯ Here we examined adult Survivin(Camcre) mice with a conditional deletion of the survivin gene in embryonic neurogenic regions. Although the deletion of survivin had no effect on basic excitability in DG and CA1-region, there was a marked impairment of long-term potentiation (LTP) in these areas. Our data support a function of survivin in hippocampal synaptic plasticity and learning and underline the importance of adult brain neurogenesis for proper operation of the hippocampal tri-synaptic circuit and the physiological functions that depend on it.