Neuroscience
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Comparative Study
The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain.
The cortical stab injury has been widely used for biochemical analysis of molecular changes following CNS injury. However, the cellular responses to this injury have not been accurately quantified. In order to provide a baseline for biochemical studies and future experiments on the manipulation of the CNS injury response we have undertaken a quantitative analysis of this injury. ⋯ They are likely to be blood-derived cells that express NG2 or have ingested it. NG2 immunohistochemistry and platelet-derived growth factor alpha receptor (PDGFalpha-R) in situ hybridisation on neighbouring sections was performed. In the lesioned area only 12% of NG2 positive (+ive) cells were PDGFalpha-R +ive (a ratio of 1:8 for PDGFalpha-R +ive cells: NG2 +ive cells) compared with 33% in the unlesioned cortex and an almost 100% overlap in the spinal cord.
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Using an in vitro microsuperfusion procedure, the release of newly synthesized [(3)H]-acetylcholine (ACh), evoked by N-methyl-D-aspartate (NMDA) receptor stimulation, was investigated in striosome-enriched areas and matrix of the rat striatum. The role of micro-opioid receptors, activated by endogenously released enkephalin, on the NMDA-evoked release of ACh was studied using the selective micro-opioid receptor antagonist, beta-funaltrexamine. Experiments were performed 2 (morning) or 8 (afternoon) h after light onset, in either the presence or absence (alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis) of dopaminergic transmission. ⋯ The selective micro-opiate agonist, [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (1 microM, coapplied with NMDA), was without effect on the NMDA-evoked release of ACh but abolished both dopamine-dependent (morning) and dopamine-independent (afternoon) responses of beta-funaltrexamine (10 nM and 1 microM). Therefore, in the limbic territory of the striatum enriched in striosomes, the micro-opioid-inhibitory regulation of ACh release follows diurnal rhythms. While dopamine is required for this regulation in the morning and the afternoon, an additional dopamine-independent process is present only in the afternoon.
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Comparative Study
Knockdown of spinal cord postsynaptic density protein-95 prevents the development of morphine tolerance in rats.
The activation of spinal cord N-methyl-D-aspartate (NMDA) receptors and subsequent intracellular cascades play a pivotal role in the development of opioid tolerance. Postsynaptic density protein-95 (PSD-95), a molecular scaffolding protein, assembles a specific set of signaling proteins around NMDA receptors at neuronal synapses. The current study investigated the possible involvement of PSD-95 in the development of opioid tolerance. ⋯ The PSD-95 antisense oligodeoxynucleotide at the doses we used did not affect baseline response to noxious thermal stimulation or locomotor function. The present study indicates that the deficiency of spinal cord PSD-95 attenuates the development of opioid tolerance. These results suggest that PSD-95 might be involved in the central mechanisms of opioid tolerance and provide a possible new target for prevention of development of opioid tolerance.
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Comparative Study
Skilled-learning-induced potentiation in rat sensorimotor cortex: a transient form of behavioural long-term potentiation.
The relation between the acquisition of a skilled motor task and synaptic plasticity in the sensorimotor cortex of the awake, freely behaving rat was examined. Skilled-motor training was previously found to induce a functional reorganization of the caudal forelimb area, and to induce an increase in synaptic efficacy, measured in vitro, on the side contralateral to the reaching forelimb. Here, we repeatedly measured neocortical evoked potential recordings in awake, freely behaving rats to examine whether skilled training would induce changes in polysynaptic efficacy on the side contralateral to the reaching forelimb. ⋯ We also tested the hypothesis that skilled learning induced potentiation shares similar mechanisms to long-term potentiation (LTP) and long-term depression by artificially manipulating polysynaptic efficacy in skilled rats with high- and low-frequency stimulation. We observed that, compared with the ipsilateral side, less potentiation but more depression could be induced on the side contralateral to the reaching forelimb. We conclude that a transient, network-based LTP-like mechanism operates during the learning of a skilled motor task.
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Previously we reported that glutamate and neuronal nitric oxide synthase (nNOS) colocalize in neurons of the nucleus tractus solitarii (NTS). That finding provided anatomical support for the suggestion that nitric oxide and glutamate interact in cardiovascular regulation by the NTS. Here we test the hypothesis that nNOS colocalizes with vesicular glutamate transporters (VGluT1 and VGluT2) in the NTS. ⋯ When compared with the other NTS subnuclei, the dorsolateral, gelatinosus and subpostremal subnuclei had higher frequencies of colocalization of VGluT2-IR and nNOS-IR. VGluT2-IR positive fibers were also apposed to nNOS-IR positive fibers throughout the NTS. These data support our hypothesis and confirm that glutamatergic fibers in the NTS contain nNOS.