Brain research. Molecular brain research
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Brain Res. Mol. Brain Res. · Mar 2001
Selective upregulation of the flip-flop splice variants of AMPA receptor subunits in the rat spinal cord after hindpaw inflammation.
Glutamate receptors are involved in spinal nociceptive transmission and the development of persistent inflammatory hyperalgesia. It is unclear, however, whether there are changes in glutamate receptor gene expression associated with tissue injury. In the present study, we used reverse transcription-polymerase chain reaction (RT-PCR) to examine the modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor gene expression in the rat spinal cord by inflammation. ⋯ Immunocytochemical analysis of GluR1 and GluR2 subunits indicate that the protein translation products of these subunits were also increased in the spinal cord. These results demonstrate an increased expression of AMPA receptor subunits that correlates with the acute phase of CFA-induced inflammation and hyperalgesia. Selective changes in the expression of the flip-flop splice variants of the AMPA receptor suggest a reorganization of the composition of the AMPA receptor complex and its involvement in the development of inflammatory hyperalgesia.
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Brain Res. Mol. Brain Res. · Mar 2001
Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors.
In the primary olfactory pathway axons of olfactory neurons (ONs) are accompanied by ensheathing cells (ECs) as the fibres course towards the olfactory bulb. Ensheathing cells are thought to play an important role in promoting and guiding olfactory axons to their appropriate target. In recent years, studies have shown that transplants of ECs into lesions in the central nervous system (CNS) are able to stimulate the growth of axons and in some cases restore functional connections. ⋯ RT-PCR analysis demonstrated expression of mRNA for NGF, BDNF, GDNF and neurturin (NTN). In addition, ECs also expressed the receptors trkB, GFRalpha-1 and GFRalpha-2. The results of the experiments show that ECs express a number of growth factors and that BDNF in particular could act both in a paracrine and autocrine manner.
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Controversies surround the possible long-term physiological and psychological consequences of opioid use. Analgesic tolerance and addiction are commonly at the center of these controversies, but other concerns exist as well. A growing body of evidence suggests that hyperalgesia caused by the chronic administration of opioids can occur in laboratory animals and in humans. ⋯ Finally, we explored the pharmacological sensitivities of OIH. We found that the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the heme oxygenase (HO) inhibitor tin protoporphyrin (Sn-P) dose-dependently reduced OIH in this model while the NSAID indomethacin had no effect. Thus we have characterized a murine model of OIH which will be useful in the pursuit of the molecular mechanisms underlying this phenomenon.
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Brain Res. Mol. Brain Res. · Nov 2000
Cocaine self-administration in rats differentially alters mRNA levels of the monoamine transporters and striatal neuropeptides.
The potential neuroadaptations to cocaine self-administration (SA) were evaluated using quantitative in situ hybridisation histochemistry. Levels of mRNAs of the monoamine transporters, i.e. the primary molecular targets of cocaine, and the striatal neuropeptides substance P and enkephalin, which predominantly exist in different populations of dopaminoceptive striatal neurons, were quantified in rats which had reached different stages of acquisition of cocaine SA. Thus, animals were killed 1 h after completing a self-administration session (i) early in or after acquisition of cocaine SA (ii) after various regimes of chronic cocaine SA, and (iii) a 10-day period of withdrawal from chronic cocaine intake. ⋯ Monoamine transporter expression was differentially altered by cocaine; dopamine transporter mRNA levels in the ventral tegmental area, but not in the substantia nigra, were increased following withdrawal from cocaine, suggesting a role for the upregulated mesolimbic dopamine transporter in the mechanisms underlying relapse to cocaine taking. By contrast, serotonin transporter mRNA in the dorsal raphé and noradrenaline transporter mRNA in the locus coeruleus remained unaltered under all experimental conditions. In addition, the expression of the striatal neuropeptides was also differentially altered; substance P mRNA levels were transiently increased in the shell of the nucleus accumbens by prolonged cocaine self-administration, but enkephalin mRNA levels in the dorsal and ventral striatum remained unaltered under all conditions.
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Brain Res. Mol. Brain Res. · May 2000
Seizures and sensory stimulation result in different patterns of brain derived neurotrophic factor protein expression in the barrel cortex and hippocampus.
Brain-derived neurotrophic factor (BDNF) is important for the development and trophic support of neurons, and may be involved in controlling axonal sprouting and synaptic plasticity. In order to investigate the activity-dependent regulation of the BDNF gene, BDNF expression was examined within the rat somatosensory cortex (SSC) and hippocampus following vibrissae stimulation, kainic acid induced seizure, and pentylenetetrazol (PTZ) induced seizure. The specific goals of this study were to determine the time course and magnitude of BDNF's activity-dependent expression, and to compare the expression patterns of three commonly used neuronal activation paradigms. ⋯ Finally, whisker stimulation resulted in an unexpected increase in BDNF mRNA and protein levels within the hippocampus. These results suggest specific types of neuronal activity can regulate gene expression differently. Furthermore, temporal and spatial differences between the expression of BDNF protein and mRNA levels suggest that the BDNF gene is regulated at the level of translation as well as transcription.