Brain research
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Long-term potentiation (LTP) at hippocampal mossy fiber-CA3 pyramidal neuron synapses was induced in the field excitatory postsynaptic potential (EPSP) by the delivery of HFS (a tetanus of two trains of 100 pulses at 100 Hz with a 10s interval) and was reversed (depotentiated) by a train of LFS of 1000 pulses at 2 Hz applied 60 min later. This depotentiation was triggered by activation of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) during HFS, which may increase the postsynaptic intracellular Ca(2+) concentration, leading to a cellular process responsible for modification of LTP expression at mossy fiber-CA3 synapses. Furthermore, we found that activation of IP3Rs or protein phosphatase during LFS was required for the reversal of LTP expressed at mossy fiber-CA3 synapses. These results suggest that, in hippocampal mossy fiber-CA3 neuron synapses, activation of IP3Rs by a preconditioning HFS results in modulation of IP3R activation and/or postsynaptic protein phosphorylation during a subsequent LFS, leading to a decrease in the field EPSP and the erasure of LTP.
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The bed nucleus of the stria terminalis (BST) is a limbic structure involved in cardiovascular regulation and modulation of responses to stress. The BST contains high levels of muscarinic receptors. This study was performed to find the effects of cholinergic system of the BST on the cardiovascular regulation and the baroreflex modulation in rats. ⋯ Acute ablation of the BST by cobalt chloride also significantly decreased the slope, indicating the excitatory action of the BST on the baroreflex parasympathetic component. In conclusion, we showed for the first time that microinjection of acetylcholine into the BST evokes a pressor response by activating the local muscarinic receptors. Release of Ach into the BST, probably during stress, inhibits the baroreflex, but with no stress, the BST facilitates the baroreflex.
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Inflammation and immunity play a crucial role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). CD137 is recognized as an independent costimulatory molecule of T cells and activator of monocytes. A growing body of evidence indicates that CD137 is vital for inflammation and immunity. ⋯ The elevated mRNA and protein of CD137 were detected after SAH and peaked on day 5. CD137 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH. These findings indicate the possible role of CD137 in the pathogenesis of cerebral vasospasm after SAH.
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Comparative Study
Glial NF-κB inhibition alters neuropeptide expression after sciatic nerve injury in mice.
We utilized a transgenic mouse model where nuclear factor kappa B (NF-κB) is selectively inhibited in glial fibrillary acidic protein (GFAP) expressing cells. The transgene, GFAP-IκBα-dn, overexpresses a dominant negative form of the inhibitor of NF-κB (IκBα) under the control of the GFAP promoter. In the present work, we sought to understand the impact of glial NF-κB inhibition on the expression of pain mediating sensory neuropeptides galanin and calcitonin gene related peptide (CGRP) in a model of neuropathic pain in mice. ⋯ CGRP gene expression in the DRG increased transiently on day 1 post-CCI in WT but not in GFAP-IκBα-dn mice, and no evidence of CGRP upregulation in sciatic nerve post-CCI was found. After CCI, upregulation of CD11b in sciatic nerve was less in GFAP-IκBα-dn mice compared to WT mice, indicative of less macrophage infiltration. Our results showed that glial NF-κB inhibition reduces galanin and CGRP expression, which are neuropeptides that correlate with pain behavior and inflammation after peripheral nerve injury.
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Erythropoietin (EPO) improves functional recovery after traumatic brain injury (TBI). This study was designed to investigate long-term (3 months) effects of EPO on brain remodeling and functional recovery in rats after TBI. Young male Wistar rats were subjected to unilateral controlled cortical impact injury. ⋯ Both EPO treatments significantly improved long-term sensorimotor and cognitive functional recovery after TBI. In conclusion, the beneficial effects of posttraumatic EPO treatment on injured brain persisted for at least 3 months. The long-term improvement in functional outcome may in part be related to the neurovascular remodeling induced by EPO.