Neuroscience
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The expression of enkephalin and substance P messenger RNAs was examined in the caudate-putamen of human post mortem tissue from control and Huntington's disease tissue using in situ hybridization techniques and human specific enkephalin and substance P [35S] oligonucleotides. Macroscopic and microscopic quantification of enkephalin and substance P gene expression was carried out using computer-assisted image analysis. Tissue was collected from six control cases with no sign of neurological disease and six Huntington's disease cases ranging from grades 0 to 3 as determined by neuropathological evaluation. ⋯ For the early grade (0/1) Huntington's disease cases, a heterogeneous reduction in both enkephalin and substance P messenger RNAs were noted; for enkephalin messenger RNA the striatal autoradiograms displayed a conspicuous patchy appearance. Detailed cellular analysis of the dorsal caudate revealed a striking reduction in the number of enkephalin and substance P messenger RNA-positive cells detected and in the intensity of hybridization signal/cell. These data suggest that both the "indirect" GABA/enkephalin and "direct" GABA/substance P pathways are perturbed very early in the course of the disease and that these early changes in chemical signalling may possibly underlie the onset of clinical symptoms.
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The opiate system is involved in a wide variety of neural functions including pain perception, neuroendocrine regulation, memory, drug reward, and tolerance. Such functions imply that endogenous opioid peptides should have anatomical interactions with limbic brain structures believed to be involved in the experience and expression of emotion. Using in situ hybridization histochemistry, the messenger RNA expression of the opioid precursors, prodynorphin and proenkephalin, was studied in whole hemisphere human brain tissue. ⋯ Brain regions traditionally included within the limbic system (e.g. amygdala, hippocampus, entorhinal cortex and cingulate cortex) as well as limbic-associated regions including the ventromedial prefrontal cortex and patch compartment of the neostriatum showed high prodynorphin messenger RNA expression. In contrast, high levels of proenkephalin messenger RNA were more widely expressed in the hypothalamus, periaqueductal gray, various mesencephalic nuclei, bed nucleus of the stria terminalis, and ventral pallidum; brain regions associated with endocrine-reticular-motor continuum of the limbic system. The marked anatomical dissociation between the expression of these two opioid peptide genes, seen clearly in whole hemisphere sections, indicates that distinct functions must be subserved by the prodynorphin and proenkephalin systems in the human brain.
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The differentiation of neurons involves the establishment of distinct molecular compartments which regulate neuronal shape and function. This requires targeting of specific gene products to growth-associated regions of the neuron. We have investigated the temporal and spatial regulation of SCG10 gene expression during neuronal differentiation. ⋯ In neurons which had developed polarity, the 2 kb SCG10 messenger RNA was consistently found in the cell body and axon. This study demonstrates both temporal and spatial post-transcriptional regulation of SCG10 expression which is associated with neurite outgrowth. The directed transport and positional translation of SCG10 messenger RNA provide a potential mechanism for protein targeting and the creation of molecular compartments during neuronal differentiation.
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Under control conditions, stimulation of area CA3 pyramidal cells in slices can produce inhibitory postsynaptic potentials in granule cells by a polysynaptic pathway that is likely to involve hilar neurons [Muller W. and Misgeld U. (1990) J. Neurophysiol. 64, 46-56; Muller W. and Misgeld U. (1991) J. Neurophysiol. 65, 141-147; Scharfman H. ⋯ Excitatory postsynaptic potentials were produced without bicuculline application in three of seven cells, simply by stimulating the fimbria repetitively. Thus, if bicuculline is applied to different sites in the slice, different effects occur on the inhibitory postsynaptic potentials of granule cells that are evoked by a fimbria stimulus. If bicuculline is applied to both the granule cell soma and either area CA3 or the hilus, inhibitory postsynaptic potentials are reduced, and reveal that excitatory postsynaptic potentials can be produced by the same stimulus. (ABSTRACT TRUNCATED)