Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyramidal neurones of the neocortex have been implicated in a number of neuropsychiatric diseases, such as Alzheimer's disease. Markers that may identify these cells have been investigated using a novel technique. A subpopulation of corticifugal neocortical pyramidal neurones was destroyed by the unilateral striatal injection of volkensin, a toxin that undergoes retrograde suicide transport from the site of injection. Striatal volkensin injections produced significant reductions in the number of large pyramidal neurones of the infragranular cortical layer. The selectivity of the lesion was demonstrated by the preservation of cells containing glutamic acid decarboxylase mRNA, which are considered to be cortical interneurones. Ricin, another toxic lectin, but effective as a suicide transport agent exclusively in the PNS, produced local striatal damage but no cortical cell loss. In autoradiographic binding studies of animals treated with volkensin, binding in deep neocortical layers of [3H]8-hydroxy-2-(n-dipropylamino) tetralin ([3H]8-OH-DPAT) to 5-HT1A but not of [3H]ketanserin to 5-HT2 receptors was significantly reduced. The N-methyl-D-aspartate receptor complex was investigated using the novel glycine site antagonist [3H]L-689,560, and the muscarinic M1 receptor using [3H]pirenzepine. Significant reductions in binding of [3H]L-689,560 and [3H]pirenzepine were observed in the deep neocortical layers of the animals that had been injected with volkensin. The rank order of the ligands as effective markers for this subpopulation of pyramidal neurones was [3H]8-OH-DPAT >> [3H]pirenzepine > [3H]L-689,560 >> [3H]ketanserin. These findings are thought to have advanced the understanding of the biology of pyramidal neurones. Implications for in vivo imaging treatment of neuropsychiatric conditions such as Alzheimer's disease are discussed.
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PMID:Neurotransmitter receptors of rat cortical pyramidal neurones: implications for in vivo imaging and therapy. 839 Oct 81

Cajal described both the morphology and plasticity of neurons. He summarized the structure of neurons as composed of membrane, protoplasm, Golgi apparatus, nucleus, spongioplasm and neurofibrils (cytoskeleton). He initially considered the cytoskeleton as absorbing excitation energy and forming a "conductive pathway in the protoplasm" within the neuron. Later, he viewed the neurofibrillary threads as independent, living entities and called them neurobiones. Cajal recognized neuroplasticity in development, memory, sleep, injury and dementia, as well as after exposure to cold and starvation. He noted cytoskeletal changes during these events. However, he did not causatively connect the plastic changes in neurons with the changes in cytoskeleton. Finally, Cajal proposed a theory of chemoaffinity in 1892, and modified his neurotropic theory over the next 40 years. Today we accept that changes in the cytoskeleton produce changes in neuronal morphology. The properties of the cytoskeleton and neurobione as described by Cajal are similar to those of microtubules. These long intraneuronal neurofibrils are polymers of the protein tubulin and, whilst not being living entities, are highly dynamic, sensitive to environmental stimuli, and stabilized by microtubule associated proteins (MAPs). Furthermore, Cajal was very specific in his characterization of the neurotropic factor derived from Schwann cells. Initially, he thought the chemicals attracted the axonal fibers, but later he wrote that the factor was not attractant but rather was involved in assimilation, growth and ramifications. The neurotropic hypothesis described by Cajal in Degeneration and Regeneration in the Nervous System is more similar to a neurite extension factor (NEF) than to a neurotrophic growth factor or specific chemoaffinity (attractant) molecule. S-100 beta is the major NEF found in PNS Schwann cells and CNS astroglial cells. In summary, the views of Cajal on neuroplasticity, its frequency and function, agree with the modern hypothesis of neuronal instability. This concept states that MAPs regulate microtubule stability by a S-100 beta sensitive phosphorylation processes. Serotonin, by acting on the astroglial 5-HT1A receptor, releases S-100 beta and regulates neuronal morphology and apoptosis. This neuronal-glial connection provides a fresh view for linking neuroplasticity, mental illness, and memory with changes in the cytoskeleton.
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PMID:Cajal's hypotheses on neurobiones and neurotropic factor match properties of microtubules and S-100 beta. 1214 7