Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Synapsins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed1987

Calcium-calmodulin-dependent protein kinase in hyperplastic human parathyroid glands.

The function of the parathyroid gland is closely linked to intracellular and extracellular Ca2+ concentrations. As a step toward understanding the mechanism of action of Ca2+ on the parathyroid, we examined hyperplastic human parathyroid tissue for Ca2+ and calmodulin-dependent protein kinase activity. In parathyroid homogenates, Ca2+ stimulates the phosphorylation of substrate protein in the presence of calmodulin or phospholipid. The calmodulin (CaM)-stimulated activity is present in a soluble fraction of parathyroid and can be separated from other protein kinase activities by gel filtration chromatography. The concentration dependence of CaM kinase on Ca2+ and CaM was determined using the gel filtration. The Ka values for CaM and calcium were 100 nM and 5 microM, respectively. The fraction containing the CaM kinase activity had a calculated mol wt of 5.5 X 10(5). It contained a protein with a mol wt of 4.9 X 10(4) whose phosphorylation was Ca2+ CaM dependent and a CaM-binding protein of mol wt 4.9 X 10(4) which we suggest may be the catalytic subunit of a type II Ca2+-CaM dependent protein kinase. Hyperplastic human parathyroid tissue contains a type II Ca2+-CaM dependent protein kinase which may serve an important function in Ca2+-directed metabolism.

Calcium↗
PubMed2004

Cell cultures from animal models of Alzheimer's disease as a tool for faster screening and testing of drug efficacy.

Approximately 2 million people in the United States suffer from Alzheimer's disease (AD), which is the most common cause of chronic dementia among the aging population. During the last 7 yr, excellent opportunities to screen drugs against AD have been provided by animal models of the disease. Because even in the fastest model, AD pathology does not start before the end of the second month, it has been necessary to wait at least until that age to inject drugs into the animal to assess whether they prevent, reduce, or revert synaptic impairment, plaque formation, and increase of beta-amyloid (Abeta) levels, the main features of the disease. A solution to the problems mentioned above is achieved by the present fast, efficient, and reproducible cultured cell system from animal models of AD or Abeta-associated diseases, for the screening and testing of compounds for the treatment and therapy of AD or Abeta-associated diseases.

Age Factors↗
PubMed1994

Sex-associated differences in protein 1 values in urine: immunochemical detection of protein 1 in genital tissues.

Immunochemical methods were used to analyse sex-associated differences in urinary protein 1 concentration. Spot urine from seven normal men and seven women of reproductive age was collected in four sequentially divided fractions, and protein 1 concentration in each fraction was measured by an enzyme immunoassay using the sandwich method: protein 1 values in the first of the sequential urine samples from the male subjects were remarkably high (81.4 +/- 80.4 micrograms/l; mean +/- 1 SD), but were much lower in the remaining three fractions. In females, on the other hand, protein 1 values were low (0.7 +/- 0.4 microgram/l), were uniform in all four sequential fractions, and were close to those of the last three fractions of urine from male subjects. Based on this finding, protein 1 concentration was measured in 14 specimens of seminal plasma, where concentration of protein 1 was high (1259.1 +/- 1716.5 micrograms/l; range, 201.9 to 6580.0 micrograms/l). On Western blotting, protein 1 in seminal plasma had a molecular mass of M(r) 14,000, the same as that of protein 1 purified from the urine of patients with chronic renal failure of probable plasma origin, and of concentrated male urine collected at the initiation of voiding, which is thus thought to come mainly from genital tissue. Protein 1 was found to be in high concentration (434.8 +/- 504.6 micrograms/l) in five aspirated fluids collected at the ejaculatory duct after squeezing the prostate. Three prostate tissue extracts contained protein 1 concentrations ranging from 8.6 to 50.1 micrograms/l. Protein 1 is also present in seminal vesicle fluids (7.1 +/- 2.8 micrograms/l; range, 2.3 to 9.5 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

TrkB has a cell-autonomous role in the establishment of hippocampal Schaffer collateral synapses.

Neurotrophin signaling has been implicated in the processes of synapse formation and plasticity. To gain additional insight into the mechanism of BDNF and TrkB influence on synapse formation and synaptic plasticity, we generated a conditional knock-out for TrkB using the cre/loxp system. Using three different cre-expressing transgenic mice, three unique spatial and temporal configurations of TrkB deletion were obtained with regard to the hippocampal Schaffer collateral synapse. We compare synapse formation in mutants in which TrkB is ablated either in presynaptic or in both presynaptic and postsynaptic cells at early developmental or postdevelopmental time points. Our results indicate a requirement for TrkB at both the presynaptic and postsynaptic sites during development. In the absence of TrkB, synapse numbers were significantly reduced. In vivo ablation of TrkB after synapse formation did not affect synapse numbers. In primary hippocampal cultures, deletion of TrkB in only the postsynaptic cell, before synapse formation, also resulted in deficits of synapse formation. We conclude that TrkB signaling has a cell-autonomous role required for normal development of both presynaptic and postsynaptic components of the Schaffer collateral synapse.

Animals↗
PubMed2006

Role of efficient neurotransmitter release in barrel map development.

Cortical maps are remarkably precise, with organized arrays of thalamocortical afferents (TCAs) that project into distinct neuronal modules. Here, we present evidence for the involvement of efficient neurotransmitter release in mouse cortical barrel map development using barrelless mice, a loss-of-function mutant of calcium/calmodulin-activated adenylyl cyclase I (AC1), and mice with a mutation in Rab3-interacting molecule 1alpha (RIM1alpha), an active zone protein that regulates neurotransmitter release. We demonstrate that release efficacy is substantially decreased in barrelless TCAs. We identify RIMs as important phosphorylation targets for AC1 in the presynaptic terminal. We further show that RIM1alpha mutant mice have reduced TCA neurotransmitter release efficacy and barrel map deficits, although not as severe as those found in barrelless mice. This supports the role of RIM proteins in mediating, in part, AC1 signaling in barrel map development. Finally, we present a model to show how inadequacies in presynaptic function can interfere with activity-dependent processes in neuronal circuit formation. These results demonstrate how efficient synaptic transmission mediated by AC1 function contributes to the development of cortical barrel maps.

Adenylyl Cyclases↗
PubMed2005

Postsynaptic expression of homeostatic plasticity at neocortical synapses.

Synaptic scaling is a form of homeostatic plasticity that scales synaptic strengths up or down to compensate for prolonged changes in activity. It has been controversial whether this plasticity is expressed presynaptically, postsynaptically, or both. Here we describe in detail the homeostatic changes that take place at excitatory synapses in visual cortical cultures after 1 or 2 d of activity blockade. After 7-10 d in vitro, activity blockade significantly increased postsynaptic accumulation of synaptic AMPA receptors via proportional increases in glutamate receptor 1 (GluR1) and GluR2. Time-lapse imaging of enhanced green fluorescent protein-tagged AMPA receptors revealed that receptor accumulation increased progressively over 2 d of activity blockade and affected the entire population of imaged synapses. The strength of synaptic connections between pyramidal neurons was more than doubled after activity blockade without affecting short-term depression or the coefficient of variation of the postsynaptic responses. Furthermore, uptake of the fluorescent styryl dye FM1-43 (N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl] pyridinium dibromide) by presynaptic terminals was not different at control and activity-blocked synapses. In addition to the increased accumulation of postsynaptic AMPA receptors, boosting of dendritic AMPA currents by sodium channels was increased by activity blockade. These data indicate that, at young neocortical synapses, synaptic scaling has a predominantly postsynaptic locus and functions as a gain control mechanism to regulate neuronal activity without affecting the dynamics of synaptic transmission.

Action Potentials↗
PubMed2001

Calcium and the control of mammalian cortical granule exocytosis.

At fertilization, the release of intracellular calcium is necessary and sufficient for most, if not virtually all, of the major events of egg activation that are responsible for the onset of embryonic development. In mammalian eggs, repetitive calcium oscillations stimulate egg activation events through calcium-dependent effectors, such as calmodulin, protein kinases, and specific proteins involved in exocytosis. One of the earliest calcium-dependent events is the exocytosis of cortical granules (CGs), a secretory event resulting in the block to polyspermy and the prevention of triploidy. Emerging studies suggest that CG release in mature eggs is dependent upon calcium-dependent proteins similar to those in somatic cells employed to undergo calcium-regulated exocytosis. In contrast, pre-ovulatory oocytes are incompetent to undergo CG exocytosis due to deficiencies in the ability to release and respond to increases in intracellular calcium. The development of competence to release and respond to calcium is relevant to both animal and human in vitro fertilization programs that largely utilize ovarian oocytes not all of which are fully activation competent.

Adaptor Proteins, Signal Transducing↗
PubMed1999

A new look at embryonic development of the visual system in decapod crustaceans: neuropil formation, neurogenesis, and apoptotic cell death.

In recent years, comparing the structure and development of the central nervous system in crustaceans has provided new insights into the phylogenetic relationships of arthropods. Furthermore, the structural evolution of the compound eyes and optic ganglia of adult arthropods has been discussed, but it was not possible to compare the ontogeny of arthropod visual systems, owing to the lack of data on species other than insects. In the present report, we studied the development of the crustacean visual system by examining neurogenesis, neuropil formation, and apoptotic cell death in embryos of the American lobster, Homarus americanus, the spider crab, Hyas araneus, and the caridean shrimp, Palaemonetes argentinus, and compare these processes with those found in insects. Our results on the patterns of stem cell proliferation provide evidence that in decapod crustaceans and hemimetabolous insects, there exist considerable similarities in the mechanisms by which accretion of the compound eyes and growth of the optic lobes is achieved, suggesting an evolutionary conservation of these mechanisms.

Animals↗
PubMed2000

Ionic currents of Drosophila embryonic neurons derived from selectively cultured CNS midline precursors.

In order to investigate the electrogenesis of defined cell populations, we applied an in vitro system that allows the selective culturing of individual Drosophila CNS precursors under different conditions. CNS midline (ML) precursors prepared from gastrula stage embryos gave rise to progeny cells with neuronal and glial morphology that expressed specific markers. Using whole-cell patch-clamp recordings, a detailed description of ionic currents present in this defined cell population is provided. Most ionic currents of cultured ML neurons were similar to other cultured Drosophila neurons, even though their embryonic origin is different. They displayed at least two voltage-gated potassium currents, a voltage-gated sodium, two voltage-gated calcium currents, and responded to the neurotransmitters ACh and GABA. They showed homogeneity in action potential firing properties, generating only a single spike even upon sustained depolarization. Interestingly, although the expression of the voltage-gated potassium currents appeared to be highly cell autonomous, for all other currents significant changes were observed in the presence of fiber contacts.

Acetylcholine↗
PubMed1998

[A clinical and pathological study of cerebellar medulloblastoma in adult patients].

OBJECTIVE: In order to study the clinicopathological characteristics, histogenesis and prognosis of medulloblastoma in the adult patients. METHODS: Altogether 27 patients of medulloblastoma admitted form 1974-1995 were reviewed. RESULTS: In all of the cases, age ranged from 16 to 55, (average 25.8 years) with 21 tumors localized in the cerebellar vermis, and 6 tumors in the cerebellum. Among them, 12 cases were completely while 14 cases were subtotally removed and biopsy was done in only one case. In the 21 patients to be followed up, 7 survived for 2.5-17 years after the operation, and 14 died. The average survival period was 41.6 months. One year survival rate was 71.4%, five years and ten years survival rates were 14.3% respectively. Regarding to the histological types, 14 cases were considered to be classic and 13 cases were desmoplastic by histological classification. CONCLUSION: Medulloblastoma keeps still the ability of differentiation to neurons and astrocytes confirmed by electronmicroscopy and immunohistochemical staining for Syn, NSE and GFAP. Factors considered responsible to the prognosis included age, tumor location, various therapeutic measurements and the histological classification.

Adolescent↗
PubMed1998

[A clinicopathological analysis of primitive neuroectodermal tumors of the CNS].

OBJECTIVE: To investigate the difference between cerebellar medulloblastoma (MB) and primary cerebral small cell tumor in histogenesis, morphologic features and biological behavior. METHODS: 210 cases of MB and 9 cases of small cell tumor of cerebrum were observed with histologic and immunohistochemical techniques. RESULTS: Both tumors were composed of primitive cells with focal evidence of glial and/or neuronal differentiation. In 63.2% of MB and five-eighths of small cell tumor of cerebrum coexpressed GFAP and Syn. Both types of tumors were highly malignant. The overall 1 year survival rates were 34.63% and 25.65% respectively. The survival rate was lower for patients with high proliferative index, with necrosis or without receiving radiation therapy. CONCLUSION: MB is similar to other small cell tumors of CNS in morphological features, specific marker expression and biological behavior. These tumors can be classified as primitive neuro-ectodermal tumors (PNET).

Adolescent↗
PubMed2001

Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release.

Spectrins are plasma membrane-associated cytoskeletal proteins implicated in several aspects of synaptic development and function, including presynaptic vesicle tethering and postsynaptic receptor aggregation. To test these hypotheses, we characterized Drosophila mutants lacking either alpha- or beta-spectrin. The Drosophila genome contains only one alpha-spectrin and one conventional beta-spectrin gene, making it an ideal system to genetically manipulate spectrin levels and examine the resulting synaptic alterations. Both spectrin proteins are strongly expressed in the Drosophila neuromusculature and highly enriched at the glutamatergic neuromuscular junction. Protein null alpha- and beta-spectrin mutants are embryonic lethal and display severely disrupted neurotransmission without altered morphological synaptogenesis. Contrary to current models, the absence of spectrins does not alter postsynaptic glutamate receptor field function or the ultrastructural localization of presynaptic vesicles. However, the subcellular localization of numerous synaptic proteins is disrupted, suggesting that the defects in presynaptic neurotransmitter release may be attributable to inappropriate assembly, transport, or localization of proteins required for synaptic function.

Animals↗
PubMed2002

Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABA(A) receptors clustered at neocortical synapses.

Maintaining the proper balance between excitation and inhibition is necessary to prevent cortical circuits from either falling silent or generating epileptiform activity. One mechanism through which cortical networks maintain this balance is through the activity-dependent regulation of inhibition, but whether this is achieved primarily through changes in synapse number or synaptic strength is not clear. Previously, we found that 2 d of activity deprivation increased the amplitude of miniature EPSCs (mEPSCs) onto cultured visual cortical pyramidal neurons. Here we find that this same manipulation decreases the amplitude of mIPSCs. This occurs with no change in single-channel conductance but is accompanied by a reduction in the average number of channels open during the mIPSC peak and a reduction in the intensity of staining for GABA(A) receptors (GABA(A)Rs) at postsynaptic sites. In addition, the number of synaptic sites that express detectable levels of GABA(A)Rs was decreased by approximately 50% after activity blockade, although there was no reduction in the total number of presynaptic contacts. These data suggest that activity deprivation reduces cortical inhibition by reducing both the number of GABA(A)Rs clustered at synaptic sites and the number of functional inhibitory synapses. Because excitatory and inhibitory synaptic currents are regulated in opposite directions by activity blockade, these data suggest that the balance between excitation and inhibition is dynamically regulated by ongoing activity.

Animals↗
PubMed2002

Brain-derived neurotrophic factor promotes the maturation of GABAergic mechanisms in cultured hippocampal neurons.

Brain-derived neurotrophic factor (BDNF) has been implicated in activity-dependent plasticity of neuronal function and network arrangement. To clarify how BDNF exerts its action, we evaluated the physiological, histological, and biochemical characteristics of cultured hippocampal neurons after long-term treatment with BDNF. Here we show that BDNF facilitates high K(+)-elicited release of GABA but not of glutamate and induces an increase in immunoreactive signals of glutamic acid decarboxylase, a GABA-synthesizing enzyme. The soma size of GABAergic neurons was enlarged in BDNF-treated cultures, whereas the average soma size of all neurons was virtually unchanged. BDNF also upregulated protein levels of GABA(A) receptors but not of glutamate receptors. These data imply that BDNF selectively advances the maturation of GABAergic synapses. However, immunocytochemical analyses revealed that a significant expression of TrkB, a high-affinity receptor for BDNF, was detected in non-GABAergic as well as GABAergic neurons. BDNF also increased to total amount of synaptic vesicle-associated proteins without affecting the number of presynaptic vesicles that can be labeled with FM1-43 after K(+) depolarization. Together, our findings indicate that BDNF principally promotes GABAergic maturation but may also potentially contribute to excitatory synapse development via increasing resting synaptic vesicles.

Animals↗