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At least 1,495 records · Page 83Linked to original sources
PubMed2002

Focused ultrasound ablation of the epididymis with use of thermal measurements in a canine model.

OBJECTIVE: To explore the epididymis as an alternative anatomical target to the vas deferens for noninvasive male sterilization using therapeutic focused ultrasound. DESIGN: Controlled preclinical study. SETTING: Canine animal model in an academic research environment. PATIENT(S): Four healthy male mongrel dogs (30-35 kg). INTERVENTION(S): A transducer mounted on a plastic clip delivered ultrasound energy to the canine epididymis. Thermocouples placed transcutaneously into the epididymis, intradermally, and on the skin surface recorded temperatures during ablation with a wide range of acoustic powers and sonication times (control, 3 W/120 s, 5 W/90 s, 7 W/60 s). MAIN OUTCOME MEASURE(S): Thermocouple temperature measurements determined the optimal range of ablation parameters that produced successful thermal occlusion of the epididymis without adverse effects (e.g., skin burns, testicular injury). RESULT(S): A large "therapeutic window" was determined (power = 3-7 W, time = 20-120 seconds) over which noninvasive thermal occlusion of the epididymis can be achieved. Thermal occlusion rates were higher, and complications lower, than found previously with vas deferens ablation. CONCLUSION(S): The epididymis represents a larger and easier target than the vas deferens for performing noninvasive male sterilization using focused ultrasound. Long-term azoospermia studies will be necessary to confirm permanent sterilization with this technique.

Animals↗
PubMed2007

Oculomotor plasticity: are mechanisms of adaptation for reactive and voluntary saccades separate?

Saccadic eye movements are permanently controlled and their accuracy maintained by adaptive mechanisms that compensate for physiological or pathological perturbations. In contrast to the adaptation of reactive saccades (RS) which are automatically triggered by the sudden appearance of a single target, little is known about the adaptation of voluntary saccades which allow us to intentionally scan our environment in nearly all our daily activities. In this study, we addressed this issue in human subjects by determining the properties of adaptation of scanning voluntary saccades (SVS) and comparing these features to those of RS. We also tested the reciprocal transfers of adaptation between the two saccade types. Our results revealed that SVS and RS adaptations disclosed similar adaptation fields, time course and recovery levels, with only a slightly lower after-effect for SVS. Moreover, RS and SVS main sequences both remained unaffected after adaptation. Finally and quite unexpectedly, the pattern of adaptation transfers was asymmetrical, with a much stronger transfer from SVS to RS (79%) than in the reverse direction (22%). These data demonstrate that adaptations of RS and SVS share several behavioural properties but at the same time rely on partially distinct processes. Based on these findings, it is proposed that adaptations of RS and SVS may involve a neural network including both a common site and two separate sites specifically recruited for each saccade type.

Adaptation, Ocular↗
PubMed2003

Plasticity of the GABAergic phenotype of the "glutamatergic" granule cells of the rat dentate gyrus.

The "glutamatergic" granule cells of the dentate gyrus transiently express a GABAergic phenotype when a state of hyperexcitability is induced in the adult rat. Consequently, granule cell (GC) activation provokes monosynaptic GABAergic responses in their targets of area CA3. Because GABA exerts a trophic action on neonatal CA3 and mossy fibers (MF) constitute its main input, we hypothesized that the GABAergic phenotype of the MF could also be transiently expressed early in life. We addressed this possibility with a multidisciplinary approach. Electrophysiological recordings in developing rats revealed that, until day 22-23 of age, glutamate receptor antagonists block the excitatory response evoked in pyramidal cells by GCs, isolating a fast metabotropic glutamate receptor-sensitive GABAergic response. In a clear-cut manner from day 23-24 of age, GC activation in the presence of glutamatergic antagonists was unable to evoke synaptic responses in CA3. Immunohistological experiments showed the presence of GABA and GAD67 (glutamate decarboxylase 67 kDa isoform) in the developing GCs and their MF, and, using reverse transcription-PCR, we confirmed the expression of vesicular GABA transporter mRNA in the developing dentate gyrus and its downregulation in the adult. The GABAergic markers were upregulated and MF inhibitory transmission reappeared when hyperexcitability was induced in adult rats. Our data evidence for the first time a developmental and activity-dependent regulation of the complex phenotype of the GC. At early ages, the GABAergic input from the MF may add to the interneuronal input to CA3 to foster development, and, in the adult, it can possibly protect the system from enhanced excitability.

Age Factors↗
PubMed1979

Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.

Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F-265). The effector cells were adherent and were probably monocytes. Sephadex G-10 column passage or adherence to plastic removed most growth-inhibitory activity. Adherent cells recovered from plastic flasks (88-94% monocytes) were strongly growth-inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth-inhibitory activity was not species-restricted, since human effector cells and also effector cells from tumor-bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL-5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non-adherent and have little reactivity against F-265 or RBL-5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F-265 resulted in similar degrees of reduction in the number of target cells and in [3H] thymidine uptake.

Animals↗
PubMed2006

Plasticity in brain processing and modulation of pain.

Brain processing of pain in humans is based on multiple ascending pathways and brain regions that are involved in several pain components, such as sensory, immediate affective, and secondary affective dimensions. These dimensions are processed both serially and in parallel. They include spinal ascending pathways that directly target limbic and brainstem structures involved in pain-related emotions as well as a pathway proceeding from the somatosensory cortices to limbic cortical areas. Superimposed on this neural organization is the capacity to process the dimensions of pain in multiple ways, as in patients who lack one cerebral hemisphere but can nevertheless locate and rate pain intensity and pain unpleasantness on both sides of the body. The dimensions of pain also can be psychologically modulated in multiple ways and these changes are accompanied by corresponding changes in relevant brain structures. Finally, understanding psychological modulation of pain and pain-related brain activity is optimized by a scientific framework that integrates principles of contemporary physics, neuroscience, and human experiential science.

Animals↗
PubMed1994

Plasticity of postganglionic sympathetic neurons in the rat superior cervical ganglion after axotomy.

The neuropeptides galanin (GAL) and vasoactive intestinal polypeptide (VIP) are upregulated in spinal and vagal sensory as well as in cranial motor neurons after axonal transection. In this study an increase of both peptides is demonstrated in axotomized principal ganglionic neurons (PGN) of the rat sympathetic superior cervical ganglion by use of double-labeling immunofluorescence. Compared to control ganglia that do not contain more than 1% GAL- or VIP-positive cells, about 26% of all PGN exhibit GAL immunoreactivity by day 1 after transection of the major postganglionic branches. The proportion of immunoreactive neurons reaches its maximum after 30 days (40%) and decreases to about 27% within the second month after axotomy. The percentage of VIP-positive neurons is much lower than for GAL: 2% of the PGN exhibit VIP immunoreactivity at day 1 and about 7% are observed 30 and 60 days after axotomy. In order to further characterize newly GAL- and VIP-positive PGN, their cell diameters were determined 12 days after axotomy. Compared to the mean overall neuron diameter of 24.8 microns, GAL-immunoreactive neurons are predominantly of small and intermediate size (22.2 microns), whereas VIP occurs mainly in larger neurons (26.1 microns). Besides cell bodies, many intraganglionic nerve fibers stain positive for GAL or VIP, particularly at day 6. Most likely, these fibers represent axons, as indicated by the absence of MAP2, a cytoskeletal protein found in neuronal somata and dendrites. They establish direct membrane contacts with postganglionic perikarya, as revealed by pre-embedding immuno-electron microscopy. Some cell bodies and fibers contain both peptides. Colocalization of GAL or VIP with tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis, reveals a reduced immunoreactivity for TH in intensely GAL- or VIP-positive cells, and vice versa at day 6. However, no difference in staining intensity for VIP or GAL, and TH, is observed after 30 and 60 days. Possible implications of GAL and VIP for peripheral nerve regeneration and their regulation by target-derived factors are discussed.

Animals↗
PubMedDate not supplied

Behavioral plasticity of Myrmica rubra ants during learning in a multi-alternative symmetrical labyrinth.

The problem of behavioral plasticity in insects was studied with red ants, Myrmica rubra, by altering a habit developed in a multi-alternative labyrinth with care for offspring as motivation. In altering the habit, location of reinforcement was changed: in the first series, the brood was transferred from the target areas to relatively symmetrical areas of the transverse axis of the labyrinth; in the second, reinforcement was left on one area that had not been preferred during learning of the target area. In both situations, the ants displayed the ability to alter labyrinth habits. The first alteration was the more complex, and 62.5% of the ants were able to manage it while 87.5% managed the second. Such indices as the first correct solution, the average number of movements in the cycle, and total number of correct cycles were also poorer for the first alteration. Development of a new motor habit was accompanied by a change (intensification) of the initial spatial-motor asymmetry. Individual variability in ant behavior were more evident in alterations. The animals not able to manage alterations exhibited definite preneurotic traits. It is suggested that ants have high plasticity and ability to successfully modify their behavior to correspond to change in the experimental situation.

Animals↗
PubMed1997

Intracerebroventricular infusion of the NMDA receptor-associated glycine site antagonist 7-chlorokynurenate impairs water maze performance but fails to block hippocampal long-term potentiation in vivo.

Most previous studies investigating the relationship between N-methyl-D-aspartate receptor-dependent synaptic plasticity and learning have employed drugs that either compete with glutamate for access to the primary agonist binding site (e.g., D-2-amino-5-phosphopentanoic acid) or block the associated ion channel (e.g., dizocilpine). This study targeted the glycine receptor site located on the NMDA receptor complex. Chronic intracerebroventricular infusion of the glycine site antagonist 7-chlorokynurenate (7CK; 75 mM, 0.5 microliter/h, icv, for up to 14 days) impaired performance of male Lister hooded rats during acquisition of a spatial reference memory task in the water maze. In addition, however, these animals showed sensorimotor deficits, including a prolonged righting reflex, ataxia, and difficulty in staying on the escape platform. On completion of behavioral testing, the rats were anesthetized with urethane and an attempt was made to induce LTP in the hippocampus ipsilateral to the infusion cannula. Both control and 7CK-infused animals displayed equivalent long-term potentiation (LTP) 60 min posttetanus. A novel analytical technique for assaying drug tissue levels involving high-performance liquid chromotography with fluorescence detection revealed that tissue levels of 7CK in hippocampus were extremely low and unlikely to be sufficient to affect LTP, as observed. These findings neither support nor compromise the LTP/learning hypothesis, but they illustrate some of the problems of using drugs to elucidate the neurobiological mechanisms of learning and memory and the importance of a within-subjects design incorporating behavioral, physiological, and biochemical measures.

Animals↗
PubMed1996

Molecular and cellular plasticity in developing epileptic brain.

Defined transgenic models of epilepsy in the mouse represent unique opportunities to examine interactions between synchronous synaptic activity and cellular programs of brain development. We are beginning to acquire a list of the kinds of genes favoring sudden, intermittent aberrant discharges in central neurons, and we have found that, rather than arising from a few gene superfamilies regulating membrane excitability, they are involved in many diverse functions of the cell. Whereas some primary gene defects impinge directly on membrane electrogenesis and neurotransmitter signaling at synapses, others are too far removed from these processes to clearly visualize the steps by which they promote epileptogenesis. We have tantalizing evidence that several, and probably all, epilepsy genes entrain some degree of secondary molecular and cellular plasticity, and we can guess that these downstream rearrangements may account for the delayed onset of epileptic phenotypes in some syndromes. It is too early to tell whether these, or other induced changes, provide the basis for the reversibility of some epilepsies. The diversity of epilepsy genes and their intervening cellular phenotypes promise to provide a rich source of novel molecular targets for therapeutic discovery and will have a lot to teach us in the future about the developmental potential of neural circuits in the mammalian brain.

Animals↗
PubMed1993

Regulatory subunits of cAMP-dependent protein kinases are degraded after conjugation to ubiquitin: a molecular mechanism underlying long-term synaptic plasticity.

In Aplysia, behavioral sensitization of defensive reflexes and the underlying presynaptic facilitation of sensory-to-motor neuron synapses lasts for several minutes (short term) or days to weeks (long term). Short-term sensitization has been explained by modulation of ion-channel function through cAMP-dependent protein phosphorylation. Long-term facilitation requires additional molecular changes including protein synthesis. A key event is the persistent activation of the cAMP-dependent protein kinase at baseline concentrations of cAMP. This activation is due to selective loss of regulatory (R) subunits of PKA without any change in catalytic (C) subunits. To understand the molecular mechanisms that produce the loss of R subunits in long-term facilitation, we investigated how R subunits are degraded in extracts of Aplysia nervous tissue and in rabbit reticulocyte lysates. Degradation of Aplysia R subunits requires ATP, ubiquitin, and a particulate component that appears to be the proteasome complex. Degradation is blocked by hemin, which causes the accumulation of high molecular weight derivatives of R subunits that are likely to be ubiquitin conjugates of R subunits and intermediates in the degradative pathway. We also show that vertebrate RI and RII subunits can be degraded through the ubiquitin pathway. We suggest that degradation is initiated by cAMP, which causes the holoenzyme to dissociate and, further, that the altered R-to-C ratio in Aplysia sensory neurons is maintained in long-term facilitation by newly synthesized proteins that help target R subunits for accelerated degradation.

Animals↗
PubMed2000

Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II.

Synaptic plasticity is thought to be a key process for learning, memory and other cognitive functions of the nervous system. The initial events of plasticity require the conversion of brief electrical signals into alterations of the biochemical properties of synapses that last for much longer than the initial stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin-dependent protein kinase IIalpha (CaMKII), sequentially translocates to postsynaptic sites, undergoes autophosphorylation and gets trapped for several minutes until its dissociation is induced by secondary autophosphorylation and phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation for several minutes. This suggests that trapping of CaMKII by its targets and priming of CaMKII translocation may function as biochemical memory mechanisms that change the signaling capacity of synapses.

Aniline Compounds↗
PubMed2000

Activity-dependent regulation of neuronal plasticity and self repair.

Plasticity is an essential characteristic of the brain: it is part of how the brain functions and is continuous while the brain interacts with the outer world. The state of activation and the level of activity of the entire organism affect the brain's plastic response. Brain plasticity has many substrates, ranging from synapses to neurites and entire cells. The production of new neurons is part of plasticity even in the adult and old brain, but under normal conditions neurogenesis only occurs in two privileged regions of the adult brain: hippocampus and olfactory system. At least in the hippocampus, physical activity stimulates neurogenesis by acting on the proliferation of neuronal stem cells. More specific functions such as learning may be able to recruit new neurons from the pool of cells with neurogenic potential. In a broader context neuronal stem cells can likely be found throughout the brain. Therefore, novel approaches to neuroregeneration will, when most effective, make use of the activity-related effects on neuronal stem cells in the adult brain to activate these stem cells in a targeted manner to enhance brain function.

Animals↗
PubMed2002

Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning.

The HNK-1 carbohydrate epitope, a sulfated glucuronic acid at the non-reducing terminus of glycans, is expressed characteristically on a series of cell adhesion molecules and is synthesized through a key enzyme, glucuronyltransferase (GlcAT-P). We generated mice with a targeted deletion of the GlcAT-P gene. The GlcAT-P -/- mice exhibited normal development of gross anatomical features, but the adult mutant mice exhibited reduced long term potentiation at the Schaffer collateral-CA1 synapses and a defect in spatial memory formation. This is the first evidence that the loss of a single non-reducing terminal carbohydrate residue attenuates brain higher functions.

Animals↗
PubMed1994

Precision and plasticity during Drosophila neuromuscular development.

Synaptogenesis can be analyzed in a simple array of motoneurons and muscle fibers of the embryos and larvae of Drosophila melanogaster. Each abdominal hemisegment contains a stereotypic array of 30 muscle fibers. During middle to late embryogenesis, motoneurons exit the central nervous system to make precise synaptic connections with specific muscle fibers. Target recognition has been tested using both genetic and microsurgical manipulations, which indicate that motoneurons actively recognize specific muscle fibers. The molecular basis of target recognition has been examined by screens for mutations that disrupt both guidance events and correct innervation. In addition, the motoneurons and muscle fibers both express an array of putative cell adhesion molecules whose functions may contribute to normal connectivity. Postsynaptic specializations, including glutamate receptor distribution, depend on innervation and neural activity. The neuromuscular system is not "hardwired," as motoneurons are capable of altering both their branch arborizations and connectivity in response to local denervation and blockade of synaptic function. Collectively, these studies show that the Drosophila motor innervation is a powerful model system for testing at the cellular and molecular level the mechanisms that govern synaptic development.

Animals↗
PubMed1983

Age-associated impairment of murine natural killer activity.

Natural cell-mediated cytotoxicity may be critical in the resistance displayed by animals and humans to tumors and various pathogenic microorganisms. Because the frequency of tumors and infections increases markedly in aging populations, we have compared the natural killer (NK) competence of lymphoid tissues (spleen, bone marrow) and of peritoneal cells of young adult and aged mice. Spontaneous NK activity was much lower, and the rate of target cell lysis was much less, in aged mice. The level of NK activity was only modestly increased in old, compared to young, mice when they were exposed to Trypanosoma musculi, an organism that provides strong stimulation of NK activity. Restricted NK activity of aged mice was not attributable to suppressor cells. The NK effector cells in old mice were characterized as being nonadherent to plastic, completely susceptible to lysis by complement plus an antiserum against specificity NK 1.2, and only slightly affected by treatment with antiserum against specificity Thy-1.2. Two indirect methods were employed to assess the relative frequency of splenic NK cells at the time of maximal stimulation by T. musculi: a cytotoxicity assay with antiserum against NK 1.2 and a binding assay involving monolayers of YAC-1 tumor target cells. Similar results were obtained in both assays, indicating that at maximal stimulation about 10% of the total spleen cells of both young and old mice were NK cells. We conclude (cautiously) that the functional efficiency of aged NK cells is impaired and that this defect may account, in part, for reduced ability of aged individuals to resist certain types of cancer and certain pathogenic microorganisms.

Aging↗
PubMed1987

Specific target-directed axonal outgrowth from transplanted embryonic rodent retinae into neonatal rat superior colliculus.

We have investigated whether there is evidence of target-directed growth of retinal axons to the tectum, and whether the surface of the rostral brainstem is an obligatory substrate for growing optic axons by transplanting embryonic mouse retinae to the cerebral aqueduct of neonatal rats. Such retinae emit axons that grow dorsally through the brain parenchyma to reach the superficial layers of the superior colliculus either by running dorsally along the midline, or by following a dorsally directed, radially arching course through the brain parenchyma. Studies of the early outgrowth pattern from transplanted retinae, and comparison studies of the axonal outgrowth from similarly placed cortical grafts suggest that outgrowth of retinal axons is target-directed and specific to optic axons.

Animals↗
PubMed1995

The duration of sprouted cerebrovascular axons following intracranial infusion of nerve growth factor.

We reported previously that a 2-week infusion of the trophic protein nerve growth factor (NGF) into the lateral ventricle of the adult rat brain elicits a sprouting response by perivascular axons associated with the intradural segment of the internal carotid artery. In the present study, we used electron microscopy to determine whether the sprouted axons persist following cessation of NGF delivery and, if not, to determine the time course of their disappearance. Our results demonstrate that NGF-induced sprouted axons do not persist following cessation of NGF delivery. The total number of axons at 1 week following the end of the NGF infusion was elevated compared to control values, but significantly reduced compared with NGF cases sacrificed immediately following the infusion period. Three weeks following the end of the NGF infusion, the total number of axons was similar to controls although there were no signs of axonal degeneration. These results suggest that continued elevation of NGF levels is necessary to maintain the sprouted axons and that endogenous levels of NGF, or other factors produced by the vascular target tissue, are not sufficient to maintain the newly formed axons. The demonstration that mature perivascular axons proliferate and disappear as a function of exogenous NGF exposure supports the accumulating evidence for continued plasticity in the mature nervous system.

Animals↗
PubMed1991

Shared operator recognition specificity between Trp repressor and the repressors of bacteriophage 434.

Trp repressor is the only DNA-binding regulatory protein having a helix-turn-helix motif that has been reported to engage its operator target by a mechanism termed indirect readout: the Trp repressor-DNA interface is replete with hydrogen bonds between amino acid residues and non-esterified oxygen atoms of the sugar-phosphate backbone, and contains numerous specifically positioned water molecules. In Escherichia coli mutants deleted for trpR, the immunity repressor of phage 434 led to an eightfold reduction in trp promoter utilization. The Cro434 repressor also inhibited transcription from the trp promoter. The 434 repressors, considered to interact directly with operator targets, carry recognition helices positioned near the N terminus of each protein. The DNA-recognizing elements of Trp repressor lie toward the C terminus. The trp operator thus appears to possess significant plasticity in terms of its ability to assume conformational states that allow complex formation with more than one class of regulatory protein.

Amino Acid Sequence↗