Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence and distribution of calsequestrin (CS), Ca2+ pump, and inositol 1,4,5-trisphosphate (IP3) receptor were investigated biochemically and immunologically in microsomal (P3) fractions isolated from chicken cerebrum and cerebellum. Two different batches of polyclonal antibodies specific for chicken skeletal muscle CS identified a Ca2+ binding, CS-like protein that was extremely enriched in cerebellum P3 fractions and absent from all cerebrum fractions. The cerebellum CS-like protein was deemed authentic CS because the N-terminal amino acid domain and peptide mapping were identical to those of skeletal muscle CS in the same species. CS was detected in striated muscles and cerebellum only. Cerebellum P3 fractions were also found to be considerably enriched in Ca2+ pump and IP3 receptor compared with the homologous cerebrum fractions, as judged by measurements of Ca2+ uptake, Ca2(+)-ATPase activity, IP3-induced Ca2+ release, and [3H]IP3 binding, respectively. Cerebellum microsomal fractions therefore appear to contain membrane fragments endowed with Ca2+ pump, IP3 receptor, and CS, i.e., three key components of a Ca2+ storage organelle.
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PMID:Calsequestrin, a component of the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of chicken cerebellum. 214 79

Four regions of the canine brain (frontal lobe, parieto-occipital lobe, brainstem, and cerebellum) were each fractionated by differential centrifugation into a crude mitochondrial pellet (P2) and a crude microsomal pellet (P3). Markers of endoplasmic reticulum (glucose-6-phosphate phosphatase and rotenone-insensitive NADPH cytochrome c reductase) and markers of the 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store ([3H]IP3 binding and IP3-induced Ca2+ release) were measured. No correlation was found between the two classes of markers, which suggests that the IP3 receptor does not belong to the endoplasmic reticulum in canine brain. Cerebellum P2 and P3 fractions displayed levels of [3H]IP3 binding 10- to 30-fold higher, and rates of IP3-induced Ca2+ release greater than 15-fold faster than the homologous cerebrum and brainstem fractions. Actively accumulated Ca2+ was only partially released by IP3, both before and after saponin disruption of the plasma membrane compartment. The proportion of the IP3-sensitive Ca2+ store relative to that of the total (IP3-sensitive and IP3-insensitive) Ca2+ store was variable; i.e., it was larger in cerebellum P2 (approximately 90%) than in cerebrum fractions (less than 30%). Cerebellum fractions constitute the best source from which an IP3-sensitive Ca2+ storing organelle can be purified.
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PMID:Distribution of endoplasmic reticulum and calciosome markers in membrane fractions isolated from different regions of the canine brain. 254 41

Postsynaptic densities (PSDs) have been isolated from cerebral cortex, midbrain, cerebellum, and brain stem by the Triton X-100 method previously used in the isolation of cerebral PSDs (Cohen et al., 1977, J. Cell Biol. 74:181). These PSDs have been compared in protein composition, protein phosphorylation, and morphology. Thin-section electron microscopy revealed that cerebral cortex and midbrain PSDs were identical, being approximately 57 nm thick and composed of apparent aggregates 20-30 nm in diameter. Isolated cerebellar PSDs appeared thinner (33 nm) than cerebral cortex PSDs and lacked the apparent 20- to 30-nm aggregates, but had a latticelike structure. In unidirectional and rotary-shadowed replicas, the cerebrum and midbrain PSDs were circular in shape with a large central perforation or hole in the center of them. Cerebellum PSDs did not have a large perforation, but did have numerous smaller perforations in a lattice like structure. Filaments (6-9 nm) were observed connecting possible 20- to 30-nm aggregates in cerebrum PSDs and were also observed radiating from one side of the PSD. Both cerebral cortex and midbrain PSDs exhibited identical protein patterns on SDS gel electrophoresis. In comparison, cerebellar PSDs (a) lacked the major 51,000 Mr protein, (b) contained two times less calmodulin, and (c) contained a unique protein at 73,000 Mr. Calcium plus calmodulin stimulated the phosphorylation of the 51,000 and 62,000 Mr bands in both cerebral cortex and midbrain PSDs. In cerebellar PSDs, only the 58,000 and 62,000 Mr bands were phosphorylated. In the PSDs from all brain regions, cAMP stimulated the phosphorylation of Protein Ia (73,000 Mr), Protein Ib (68.000 Mr), and a 60,000 Mr protein, although cerebrum and midbrain PSDs contained very much higher levels of phosphorylated protein than did the cerebellum. On the basis of the morphological criteria, it is possible that PSDs isolated from cerebrum and midbrain were derived from the Gray type I, or asymmetric, synapses, whereas cerebellum PSDs were derived from the Gray type II, or symmetric, synapses. Since there is some evidence that the type I synapses are involved in excitatory mechanisms while the type II are involved in inhibitory mechanisms, the role of the PSD and of some of its proteins in these synaptic responses is discussed.
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PMID:Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities. 741 Apr 81

In the present investigation, the behavior of learning and memory of 1-month and 6-month-old mice was studied by using Y-maze and one-trial passive avoidance response device. The synaptosomal free [Ca2+]i of four main brain regions (Hippocampus, Cerebral cortex, Cerebellum, Tectum of midbrain) of these mice were measured by fluorescent probe Ca2+ indicator Fura-2 and an AR-CM-MIC cation measurement system. The results showed that, in comparison with 1-month-old mice, the ability of discrimination learning and memory of 6-month-old ones were attenuated, and the synaptosomal free [Ca2+]i of hippocampus was increased.
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PMID:[Correlation between ability of learning-memory and synaptosomal free [Ca2+]i in mice of different age]. 875 89

Calretinin (CR), calbindin D-28k (CB) and parvalbumin (PV) belong to the large family of EF-hand calcium-binding proteins, which comprises more than 200 members in man. Structurally these proteins are characterized by the presence of a variable number of evolutionary well-conserved helix-loop-helix motives, which bind Ca2+ ions with high affinity. Functionally, they fall into two groups: by interaction with target proteins, calcium sensors translate calcium concentrations into signaling cascades, whereas calcium buffers are thought to modify the spatiotemporal aspects of calcium transients. Although CR, CB and PV are currently being considered calcium buffers, this may change as we learn more about their biology. Remarkable differences in their biophysical properties have led to the distinction of fast and slow buffers and suggested functional specificity of individual calcium buffers. Evaluation of the physiological roles of CR, CB and PV has been facilitated by the recent generation of mouse strains deficient in these proteins. Here, we review the biology of these calcium-binding proteins with distinct reference to the cerebellum, since they are particularly enriched in specific cerebellar neurons. CR is principally expressed in granule cells and their parallel fibres, while PV and CB are present throughout the axon, soma, dendrites and spines of Purkinje cells. PV is additionally found in a subpopulation of inhibitory interneurons, the stellate and basket cells. Studies on deficient mice together with in vitro work and their unique cell type-specific distribution in the cerebellum suggest that these calcium-binding proteins have evolved as functionally distinct, physiologically relevant modulators of intracellular calcium transients. Analysis of different brain regions suggests that these proteins are involved in regulating calcium pools critical for synaptic plasticity. Surprisingly, a major role of any of these three calcium-binding proteins as an endogenous neuroprotectant is not generally supported.
Cerebellum 2002 Dec
PMID:'New' functions for 'old' proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice. 1287 63

Metabotropic glutamate receptors (mGluRs) are a family of proteins that have seven transmembrane segments and that couple to G proteins. They differ from ionotropic glutamate receptors in that they do not form ion channels but instead affect intracellular chemical messenger systems. Eight genes coding for different subtypes of mGluRs have been identified to date and numbered accordingly in the order in which the cDNAs were cloned. Based on their principal signal-transduction capabilities in recombinant expression systems and sequence similarities, the family of mGluR subtypes is subdivided into three groups. Group 1 mGluRs (consisting of mGluR1 and 5) functionally couple to phospholipase C and affect the IP3/Ca2+ signaling pathway. The subtypes of group 2 (mGluR2 and 3) and group 3 (mGluR4, 6 7 and 8) inhibit adenylate cyclase and, thereby, mediate a decrease in cAMP concentration. All mGluR subtypes are found in the cerebellar cortex with the exception of mGluR6 which is exclusively expressed in the retina. At the parallel fiber-Purkinje cell synapses mGluR1 is localized in the peri- and extra-synaptic membrane of Purkinje cells. The main focus of this review deals with the functions of this postsynaptically localized mGluR1. These functions include (i) mediation of an inward current and a slow excitatory postsynaptic potential, and (ii) a role in induction of parallel fiber-Purkinje cell long-term depression. We discuss the mechanism underlying the mGluR1-mediated postsynaptic current as well as current theories on the role of mGluR1 in parallel fiber-Purkinje cell long-term depression.
Cerebellum
PMID:Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. 1287 70

Cerebellar long-term depression (LTD) is classically observed when climbing fibers, originating from the inferior olive, and parallel fibers, axons of granule cells, are activated repetitively and synchronously. On the basis that the climbing fiber signals errors in motor performance, LTD provides a mechanism of learning whereby inappropriate motor signals, relayed to the cerebellar cortex by parallel fibers, are selectively weakened through their repeated, close temporal association with climbing fiber activity. LTD therefore provides a cellular substrate for error-driven motor learning in the cerebellar cortex. In recent years, it has become apparent that depression at this synapse can also occur without the need for concurrent climbing fiber activation provided the parallel fibers are activated in such a way as to mobilize calcium within the Purkinje cell. A form of long-term potentiation (LTP) has also been uncovered at this synapse, which similarly relies only upon parallel fiber activation. In brain slice preparations and contrary to expectation, each of these forms of parallel fiber induced plasticity, as well as classical LTD, does not remain confined to activated parallel fibers as previously thought, but both depression and potentiation have the capacity to spread to neighboring parallel fiber synapses several tens of microns away from the activated fibers. Here, the cellular mechanisms responsible for the induction and heterosynaptic spread of parallel fiber LTP and LTD are compared to those involved in classical LTD and the physiological implications that the heterosynaptic spread of plasticity may have on cerebellar signal processing are discussed.
Cerebellum
PMID:Parallel fiber plasticity. 1287 69

Taurine efflux occurs in association with cell swelling in both hyposmotic and isosmotic conditions and during cell shrinkage in apoptotic death. Release occurs through a leak pathway, is largely Ca2+-independent and is sensitive to Cl- channel blockers. Taurine efflux elicited by hyposmolarity is reduced or suppressed by tyrosine kinase blockers and increased by tyrosine phosphatase inhibitors. The specific kinases involved are still unknown and may be different in the various cell types. Non-receptor and scr-related protein kinases have been identified in some cells as elements that directly phosphorylate the taurine efflux pathway. Possible tyrosine kinase targets are the phosphinositide kinase (PI3K), which if inhibited, prevents the osmosensitive taurine efflux in brain cells, or the small GTP-binding proteins associated with remodeling of the cytoskeleton. The similar effects of tyrosine kinase modulators on volume-activated taurine fluxes and Cl- currents are suggestive of either a shared translocation pathway or a common step in the signaling network. The effects of tyrosine kinases on taurine efflux activated in isosmotic swelling and in the release associated with apoptosis are essentially unexplored.
Cerebellum 2002 Apr
PMID:Influence of protein tyrosine kinases on cell volume change-induced taurine release. 1288 59

Several human neurological disorders have been associated with mutations in the gene coding for the alpha1 subunit of the P/Q type voltage-gated calcium channel (alpha1A/Ca(v)2.1). Mutations in this gene also occur in a number of neurologically affected mouse strains, including leaner (tg(la)/tg(la)). Because the P-type calcium current is very prominent in cerebellar Purkinje neurons, these cells from mice with alpha1 subunit mutations make excellent models for the investigation of the functional consequences of native mutations in a voltage-gated calcium channel of mammalian central nervous system. In this review, we describe the impact of altered channel function on cellular calcium homeostasis and signaling. Remarkably, calcium buffering functions of the endoplasmic reticulum and calcium-binding proteins appear to be regulated in order to compensate for altered calcium influx through the mutant channels. Although this compensation may serve to maintain calcium signaling functions, such as calcium-induced calcium release, it remains uncertain whether such compensation alleviates or contributes to the behavioral phenotype.
Cerebellum 2002 Apr
PMID:Homeostatic compensation maintains Ca2+ signaling functions in Purkinje neurons in the leaner mutant mouse. 1288 61

Low-voltage activated (LVA) Ca2+ currents have been characterized in a large variety of neurons including cerebellar Purkinje cells (PCs). This review summarizes and discusses the biophysical, pharmacological properties, as well as the molecular identity of LVA Ca2+ channels described in PCs in various experimental conditions. Putative functional roles for LVA Ca2+ currents include generation of low-threshold Ca2+ spikes (LTS) that underlie burst firing, promotion of intrinsic oscillatory behaviour, Ca2+ entry close to the resting membrane potential and synaptic potentiation. Based on our recent findings on cerebellar rat PCs in slice cultures, this review presents the major evidence demonstrating that LVA Ca2+ channels produce a dendritic initiated LTS with a regulated propagation to the soma. This new role for LVA Ca2+ channels is particularly important in determining firing patterns in PCs.
Cerebellum 2003
PMID:Dendritic low-threshold Ca2+ channels in rat cerebellar Purkinje cells: possible physiological implications. 1450 69


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