Neuroscience
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Glial cell line-derived neurotrophic factor was initially identified as a survival factor for developing midbrain dopamine neurons (for reviews, see Refs 17 and 19). Subsequent studies have demonstrated a more wide-spread role for glial cell line-derived neurotrophic factor in the developing and adult CNS. In the adult rat brain, for instance, prior administration of glial cell line-derived neurotrophic factor protects nigrostriatal dopamine neurons from 6-hydroxydopamine-induced damage. ⋯ Following extensive unilateral 6-hydroxydopamine lesions of the medial forebrain bundle, ret immunoreactivity in the substantia nigra and striatum was reduced significantly, to a similar extent as tyrosine hydroxylase immunoreactivity. In contrast, excitotoxic lesions of the striatum, achieved by intrastriatal quinolinic acid injections, resulted in increased ret staining in this brain region. In addition, marked decrements in septal ret immunoreactivity were consequent to complete transections of the fimbria-fornix.
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Neuropeptide expression in primary sensory neurons is highly plastic in response to peripheral nerve axotomy. While neuropeptide changes following complete sciatic nerve injury have been extensively studied, much less is known about the effects of partial sciatic nerve injuries on neuropeptide plasticity. Galanin. a possible endogenous analgesic peptide, was up-regulated in primary sensory neurons following complete sciatic nerve injury. ⋯ Furthermore, more galanin-immunoreactive axonal fibres were observed in the ipsilateral gracile nuclei of partially injured rats than in completely injured rats. We conclude that partial sciatic nerve injuries induced greater galanin up-regulation in medium- and large-size dorsal root ganglion neurons than complete sciatic nerve injury. Galanin expression in primary sensory neurons seems to be differentially regulated following partial and complete sciatic nerve injuries.
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Electrophysiological techniques and computational methods were used to study the effect of the selective serotonin reuptake inhibitors fluvoxamine, paroxetine and sertraline on the basal activity of dopamine neurons in the ventral tegmental area. Acute injection of fluvoxamine, paroxetine and sertraline (20-1280 microg/ kg, i.v.) caused a dose-dependent inhibition of some ventral tegmental area DA neurons but it did not affect the basal firing rate of other DA cells. A Fast-Fourier-Transformation based analysis of the basal activity of 32 ventral tegmental area DA neurons showed a positive correlation between the value of a functional operator (psi) equivalent to the density-power-spectrum of the signals and the degree of selective serotonin reuptake inhibitor-induced inhibition of ventral tegmental area DA cells. ⋯ The neurons belonging to subclass A showed a more regular behavior of the interspike interval functions corresponding to lower values detected by the functional operator psi, whereas the neurons belonging to subclass B showed a less regular behavior of interspike interval functions corresponding to higher psi values detected by the same functional operator. Fluvoxamine, paroxetine and sertraline also caused a dose-dependent increase of the percentage of spikes occurring in bursts in neurons belonging to subclass A (low values of psi), whereas the mean basal firing rate of these cells was not affected. It is suggested that this difference in density-power-spectrum could reflect the asymmetry of serotonergic input to the ventral tegmental area DA neurons, and the differential effects of selective serotonin reuptake inhibitors on these neurons might depend on the characteristics of their basal firing mode.
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Impairment in energy metabolism is thought to be involved in the aetiology of Huntington's disease. In line with this hypothesis, chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid to rats and monkeys produces selective striatal lesions similar to Huntington's disease. The present study examined whether rats treated with varying regimen of 3-nitropropionic acid could present motor abnormalities reminiscent of Huntington's disease symptomatology, correlated with Huntington's disease specific striatal symptomatology. ⋯ In these chronic animals, the degree of striatal neuronal loss was significantly correlated with the severity of spontaneous motor abnormalities, as is the case in Huntington's disease. The present study demonstrates that chronic low-dose 3-nitropropionic acid treatment in rats results in a valuable model of both the histological features and motor deficits which occur in Huntington's disease. Despite the interanimal variability in terms of response to 3-nitropropionic acid treatment, this rat model may be particularly useful for evaluating the functional benefits of new therapeutic strategies for Huntington's disease, particularly those aiming to reduce the severity of motor symptoms.
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Neurons in the central nervous system regulate their intracellular pH using particular membrane proteins of which two, namely the Na+-dependent Cl-/HCO3- exchanger and the Na+/H+ exchanger, are essential. In this study we examined messenger RNA expression and distribution of Na+/H+ exchanger in the newborn rat central nervous system and with maturation using Northern blot analysis and in situ hybridization. Our study clearly shows that each Na+/H+ exchanger has a different expression pattern in the rat central nervous system. ⋯ The messenger RNA for Na+/H+ exchanger 3, however, increased its level with age in cerebellum. From our data we conclude that: i) the expression of the Na+/H+ exchanger is age-, region-, and subtype-specific, with Na+/H+ exchanger 1 being the most prevalent in the rat central nervous system; ii) specialization of groups of neurons with respect to the type of Na+/H+ exchanger is clearly illustrated by Na+/H+ exchanger 3 which is almost totally localized in cerebellar Purkinje cells; and iii) the developmental increase in the messenger RNA for Na+/H+ exchanger 1 in the cerebral cortex and hippocampus is consistent with our previous studies on intracellular pH physiology in neonatal and mature neurons. Together this study indicates that expression of each Na+/H+ exchanger messenger RNA is differentially regulated both during development and in the different regions of rat central nervous system.