The European journal of neuroscience
-
Intra-articularly injected complete Freund's adjuvant creates in rats a chronic monoarthritis suitable for studying neuronal plasticity and chronic pain. Using such a model, we report electrophysiological and morphological evidence of alterations in somatosensory synaptic function. In arthritic rats, the baseline activity of dorsal spinal cord wide dynamic range or nociceptive-specific neurons was greater than in control animals. ⋯ Morphological examination revealed significantly increased expression of substance P and its receptor within the superficial dorsal horn of monoarthritic animals. These unique functional and chemical changes reflect alterations in both presynaptic and postsynaptic mechanisms in nociceptive transmission at the spinal level. Thus, although treatment of arthritis should obviously target its peripheral aetiology, targeting its central components is a logical therapeutic complementary objective.
-
Comparative Study
Involvement of spinal cord nuclear factor kappaB activation in rat models of proinflammatory cytokine-mediated pain facilitation.
Proinflammatory cytokines, such as interleukin-1beta and tumour necrosis factor-alpha, are released by activated glial cells in the spinal cord and play a major role in pain facilitation. These cytokines exert their actions, at least partially, through the activation of the transcription factor, nuclear factor kappaB (NF-kappaB). In turn, NF-kappaB regulates the transcription of many inflammatory mediators, including cytokines. ⋯ No or low levels of IkappaBalpha mRNA were detected in the lumbar spinal cord of vehicle-injected rats, whereas IkappaBalpha mRNA expression was markedly induced in the spinal cord following intrathecal gp120 in predominantly astrocytes and endothelial cells. Moreover, IkappaBalpha mRNA expression positively correlated with proinflammatory cytokine protein levels in lumbosacral cerebrospinal fluid. Together, these results demonstrate that spinal cord NF-kappaB activation is involved, at least in part, in exaggerated pain states.
-
Comparative Study
Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation.
Co-localization of dopamine D1 and D3 receptors in striatal neurons suggests that these two receptors interact at a cellular level in mediating dopaminergic function including psychostimulant-induced behaviour. To study D1 and D3 receptor interactions in cocaine-mediated effects, cocaine-induced locomotion and reward in mice lacking either D1, D3 or both receptors were analysed. Spontaneous locomotor activity was increased in D1-/- and D1-/-D3-/- mice and D1-/-D3-/- mice did not exhibit habituation of spontaneous rearing activity. ⋯ After repeated administration of 2.5 mg/kg of cocaine, D1-/- mice had lower pCREB levels in caudate-putamen and nucleus accumbens. Our findings suggest that, although spontaneous and cocaine-induced horizontal activity depended mainly on the presence of the D1 receptor, there may be crosstalk between D1 and D3 receptors in rearing habituation and the perception of cocaine reward at low doses of the drug. Furthermore, alterations in pCREB levels were associated with changes in cocaine-induced locomotor activity but not reward.
-
We reported previously that 96 h of sleep deprivation (SD) reduced cell proliferation in the dentate gyrus (DG) of the hippocampus in adult rats. We now report that SD reduces the number of new cells expressing a mature neuronal marker, neuronal nuclear antigen (NeuN). Rats were sleep-deprived for 96 h, using an intermittent treadmill system. ⋯ The percentages of BrdU-labeled cells co-expressing markers of immature neuronal (DCX) or glial (S100-beta) cells were not different in SD and CT groups. Thus, SD reduces neurogenesis in the DG by affecting both total proliferation and the percentage of cells expressing a mature neuronal phenotype. We hypothesize that sleep provides anabolic or signaling support for proliferation and cell fate determination.
-
Comparative Study
Time-sensitive enhancement of motor learning with the less-affected forelimb after unilateral sensorimotor cortex lesions in rats.
Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) results in time-dependent changes in neuronal activity, structure and connectivity in the contralateral motor cortex of adult rats. These changes have been linked to facilitation of motor skill learning in the less-affected/ipsilesional forelimb, which is likely to promote its use in the development of behavioral compensation. The goal of this study was to determine whether an early post-lesion-sensitive time period exists for this enhanced learning and whether it is linked to synaptogenesis in the contralesional motor cortex. ⋯ In layer V of the contralesional motor cortex, stereological methods for light and electron microscopy revealed significantly more total, multisynaptic bouton and perforated synapses per neuron compared with sham-operates, but there were no significant differences between early- and late-trained lesion groups. Thus, there appears to be a sensitive time window for the maximal expression of the enhanced learning capacity of the less-affected forelimb but this window is broadly, rather than sharply, defined. These results indicate that relatively long-lasting lesion-induced neuronal changes are likely to underlie the facilitation of learning with the less-affected forelimb.