Neuroscience
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Dysfunction of subcortical serotoninergic neurons has been implicated in some behaviour disturbances. The serotoninergic neurons in the dorsal and median raphe project widely in the brain. They innervate the olfactory bulbs and can be targets for exogenous agents attacking the olfactory epithelium and bulbs. ⋯ In spite of this the animals, as adults, had a severe serotonin depletion in the cerebral cortex and hippocampus, and showed abnormal locomotor and explorative behaviour as well as learning deficits. The neocortex was histologically intact and parameters related to other neurotransmitters such as dopamine, noradrenaline, GABA and acetylcholine showed no marked changes. A relatively selective damage to serotoninergic nuclei as a result of virus neuroinvasion through a natural portal of entry, may constitute a new pathogenetic mechanism for cortical dysfunction and behavioural deficits.
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Comparative Study
Characterization and regional distribution of strychnine-insensitive [3H]glycine binding sites in rat brain by quantitative receptor autoradiography.
Recent evidence suggests that a strychnine-insensitive glycine modulatory site is associated with the N-methyl-D-aspartate receptor-channel complex. A quantitative autoradiographic method was used to characterize the pharmacological specificity and anatomical distribution of strychnine-insensitive [3H]glycine binding sites in rat brain. [3H]Glycine binding was specific, saturable, reversible, pH and temperature-sensitive and of high affinity. [3H]Glycine interacted with a single population of sites having a KD of approximately 200 nM and a maximum density of 6.2 pmol/mg protein (stratum radiatum, CA1). Binding exhibited a pharmacological profile similar to the physiologically defined strychnine-insensitive glycine modulatory site. ⋯ The distribution of strychnine-insensitive [3H]glycine binding was heterogeneous with the following rank order of binding densities: hippocampus greater than cerebral cortex greater than caudate-putamen greater than or equal to thalamus greater than cerebellum greater than brain stem. This distribution of binding was correlated with N-methyl-D-aspartate-sensitive [3H]glutamate binding (r2 = 0.77; P less than 0.001; Pearson product-moment) and [3H]thienylcyclohexylpiperidine binding (r2 = 0.72; P less than 0.001). These observations are consistent with the hypothesis that the strychnine-insensitive glycine binding site is closely associated with the N-methyl-D-aspartate receptor-channel complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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The regional, cellular and subcellular distribution of GABA, GABA receptors and benzodiazepine receptors was investigated by light and electron microscopy in the human lumbar spinal cord taken post-mortem from eight cases aged 20-76 years. Firstly, the regional distribution of GABA receptors and benzodiazepine receptors was studied using autoradiography following in vitro labelling of cryostat sections with tritiated ligands. This was followed by a detailed study of the cellular and subcellular distribution and localization of GABA and benzodiazepine/GABAA receptors by light and electron microscopy using immunohistochemical techniques with monoclonal antibodies to GABA and to the alpha and beta subunits of the benzodiazepine/GABAA receptor complex. ⋯ Benzodiazepine/GABAA receptors were localized within the same types of synaptic complexes in which GABA-immunoreactive axon terminals were found. In these synaptic complexes, benzodiazepine/GABAA receptor immunoreactivity was associated with presynaptic and postsynaptic membranes and on apparent non-synaptic membranes. These results show a high concentration of GABA, GABA receptors and benzodiazepine receptors in lamina II of the dorsal horn of the human spinal cord and suggest a possible role for GABA in spinal sensory functions.
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Electrical stimulus intensity, capsaicin, excitatory amino acid antagonists and the substance P antagonist, spantide, have been used to investigate the roles of primary afferent C fibres and excitatory amino acid receptors in the generation of long duration (half time 9.1 s +/- 1.1 S. E. M., N = 24) contralateral reflexes recorded in ventral roots of immature rat spinal cords in vitro. ⋯ The depressant effect of spantide, unlike that of (+/-)-2-amino-5-phosphonopentanoic acid, was associated with a long lasting excitatory action. In the presence of tetrodotoxin (0.1 microM), spantide (33 microM) failed to antagonize substance P-induced depolarizations. It is suggested that long duration of the dorsal root-evoked contralateral ventral root potential is a consequence of the activation of the N-methyl-D-aspartate receptor operated ion channels by excitatory amino acid transmitters.
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Comparative Study
Dopamine high-affinity transport site topography in rat brain: major differences between dorsal and ventral striatum.
Investigations were conducted to determine the topography of the high-affinity dopamine uptake process within the rat striatum. [3H]Dopamine uptake into crude synaptosomes prepared from micropunch samples was found to be two- to three-fold higher in dorsal caudate-putamen relative to nucleus accumbens septi. In contrast, the concentrations of dopamine in the two regions were equivalent. The recognition site associated with high-affinity dopamine uptake was labeled using [3H]mazindol, and the binding of this ligand was also found to be two- to three-fold higher in homogenates from dorsal caudate-putamen samples relative to nucleus accumbens septi. ⋯ Further autoradiographic studies revealed less striatal heterogeneity in the pattern of binding of [3H]ketanserin, another radioligand associated with the striatal dopaminergic innervation but not linked to the dopamine uptake process of the plasma membrane. The findings suggest that the dopaminergic fibers of the ventral striatum, especially the medial nucleus accumbens septi, may be relatively lacking in their capacity for dopamine uptake following its release. This organization may result in regional differences in the time-course of of extraneuronal dopamine following transmitter release and may render the dopamine-containing terminals of the ventral striatum less susceptible to the degenerative influences of neurotoxins that are incorporated by the high-affinity dopamine uptake process.