Cellular and molecular neurobiology
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Cell. Mol. Neurobiol. · Nov 2013
Clonidine suppresses the induction of long-term potentiation by inhibiting HCN channels at the Schaffer collateral-CA1 synapse in anesthetized adult rats.
Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 synapse of rat hippocampus in vivo. ⋯ Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 μM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 μM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 μM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer collateral-CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.
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Cell. Mol. Neurobiol. · Nov 2013
Interleukin-1β plays key roles in LPA-induced amplification of LPA production in neuropathic pain model.
Lysophosphatidic acid (LPA) is a bioactive lipid mediator that exerts a wide range of biological actions. In recent decades, LPA has been demonstrated as an important initiator of neuropathic pain based on the mechanisms of LPA-induced feed-forward LPA amplification. In this study, we examined the possible involvement of interleukin (IL)-1β in such LPA production. ⋯ Moreover, enzyme assay experiments showed that LPA (i.t.) significantly activated calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) in the spinal dorsal horn at 1 and 2 h, respectively, and these biochemical changes were also significantly inhibited by IL-1β-neutralizing antibody. Similarly, IL-1β-neutralizing antibody reversed LPA-induced neuropathic pain-like behavior. These findings suggest that the early release of IL-1β is involved in LPA-induced amplification of LPA production, which underlies the initial mechanisms of LPA-induced neuropathic pain.