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At least 433 records · Page 24Linked to original sources
PubMed2005

Repetitive transcranial magnetic stimulation induces kf-1 expression in the rat brain.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach used for stimulating the brain, and has proven effective in the treatment of depression, however the mechanism of its antidepressant action is unknown. Recently, we have reported the induction of kf-1 in rat frontal cortex and hippocampus after chronic antidepressant treatment and repeated electroconvulsive treatment (ECT). In this study, we demonstrated the induction of kf-1 after rTMS in the rat frontal cortex and hippocampus, but not in hypothalamus. Our data suggest that kf-1 may be a common functional molecule that is increased after antidepressant treatment, ECT and rTMS. In conclusion, it is proposed that induction of kf-1 may be associated with the treatment induced adaptive neural plasticity in the brain, which is a long-term target for their antidepressant action.

Animals↗
PubMed2004

Tracing functional circuits using c-Fos regulated expression of marker genes targeted to neuronal projections.

We have developed novel techniques to trace functionally activated circuits and synaptic plasticity within the brain. We have generated transgenic mice, FTL, which contain a tau-lacZ fusion gene regulated by the promoter for c-fos. Following a particular nervous system stimulation in these mice, only neurons, which are functionally activated, will express LacZ, which is targeted to neuronal processes by the tau protein. In the FTL mice, we found highly inducible expression of lacZ by a range of different stimuli, and successful targeting of expression to neuronal cell bodies, axons and dendrites. To test if a functionally activated circuit could be visualized, the mice were deprived of water, which activates nuclei involved in body fluid homeostasis. LacZ was induced in these nuclei and their projections, allowing the mapping of a neuroendocrine circuit. Further studies have employed these mice in the analysis of neurons and circuits activated in vision, and learning and memory. We have also developed methods to measure markers of synaptic plasticity in the brain, and found significant experience dependent changes in the levels of these markers in different parts of the brain. We believe these techniques will aid in the identification of circuits for many different brain functions, and within those circuits, the locations of synaptic plasticity.

Animals↗
PubMed2006

Simultaneous determination of gaseous and particulate chlorinated polycyclic aromatic hydrocarbons in emissions from the scorching of polyvinylidene chloride film.

An analytical method for the determination of gaseous and particulate chlorinated polycyclic aromatic hydrocarbons (ClPAHs) was investigated. By means of this method, concentrations and isomer profiles of the 27 target ClPAHs could be analyzed. To evaluate the usefulness of the method for analyzing ClPAH emissions, laboratory-scale scorching tests were performed on polyvinylidene chloride (PVDC) plastic wrap over a flame of the gas burner. Only seven of the target ClPAHs were detected, and all compounds detected had 2, 3, or 4 rings. The detected ClPAHs were present in both the particulate phase and the gaseous phase, but they were present at higher concentrations in the gaseous phase than in the particulate phase. Relationships between the number of chlorine substituents on the naphthalene/phenanthrene rings and the overall concentration and the percentage in the particulate phase were also investigated.

Air Pollutants↗
PubMedDate not supplied

Age-related decrease in sympathetic sprouting is primarily due to decreased target receptivity: implications for understanding brain aging.

Aging of the nervous system is characterized by reduced anatomical plasticity. The cause of this decreased plasticity is not known because it is usually not possible to distinguish between extrinsic and intrinsic factors that affect neuronal growth. One example of age-related reduced neuronal plasticity that is amendable to such analysis is the growth of sympathetic axons into the rat hippocampal formation following septal denervation. This sprouting response can be elicited throughout the lifespan of the rat but is drastically reduced in aged animals. The age-related reduction in ingrowth could theoretically be due to decreased receptivity of the target (reduced trophic support or increased inhibition of growth), decreased responsivity of the sympathetic neurons or a combination of both factors. In order to test the relative contributions of the age of the target tissue and the age of the sympathetic neurons to the reduced growth observed in aged animals, superior cervical ganglia were transplanted from young animals into old animals (y/o) and from old animals into young animals (o/y) as well as autologously within the same animals (y/y and o/o). The extent of sympathetic ingrowth and the survival of transplanted neurons were assessed with fluorescence histochemical methods. The extent of ingrowth was significantly greater in young hosts compared with old hosts regardless of the age of the donor. In addition, the survival of transplanted neurons was greater in younger hosts than in aged hosts regardless of donor age. These results indicate that sympathetic ingrowth is reduced in aging primarily because of decreased receptivity of the hippocampal target tissue.

Adrenergic Fibers↗
PubMed2004

The characteristics and neuronal substrate of saccadic eye movement plasticity.

Saccadic eye movements are shifts in the direction of gaze that rapidly and accurately aim the fovea at targets of interest. Saccades are so brief that visual feedback cannot guide them to their targets. Therefore, the saccadic motor command must be accurately specified in advance of the movement and continually modified to compensate for growth, injury, and aging, which otherwise would produce dysmetric saccades. When a persistent dysmetria occurs in subjects with muscle weakness or neural damage or is induced in normal primates by the surreptitious jumping of a target forward or backward as a saccade is made to acquire the target, saccadic amplitude changes to reduce the dysmetria. Adaptation of saccadic amplitude or direction occurs gradually and is retained in the dark, thus representing true motor plasticity. Saccadic adaptation is more rapid in humans than in monkeys, usually is incomplete in both species, and is slower and less robust for amplitude increases than decreases. Adaptation appears to be motor rather than sensory. In humans, adaptation of saccades that would seem to require more sensory-motor processing does not transfer to saccades that seem to require less, suggesting the existence of distributed adaptation loci. In monkeys, however, transfer from more simple to more complex saccades is robust, suggesting a common adaptation site. Neurophysiological data from both species indicate that the oculomotor cerebellum is crucial for saccadic adaptation. This review shows that the precise, voluntary behaviors known as saccadic eye movements provide an alternative to simple reflexes for the study of the neuronal basis of motor learning.

Adaptation, Physiological↗
PubMed2003

Sunrise at the synapse: the FMRP mRNP shaping the synaptic interface.

Recent studies provide new insight into the mechanistic function of Fragile X Mental Retardation Protein (FMRP), paving the way to understanding the biological basis of Fragile X Syndrome. While it has been known for several years that there are spine defects associated with the absence of the mRNA binding protein FMRP, it has been unclear how its absence may lead to specific synaptic defects that underlie the learning and cognitive impairments in Fragile X. One hypothesis under study is that FMRP may play a key role in the regulation of dendritically localized mRNAs, at subsynaptic sites where regulation of local protein synthesis may influence synaptic structure and plasticity. This review highlights recent progress to identify the specific mRNA targets of FMRP and assess defects in mRNA regulation that occur in cells lacking FMRP. In addition, exciting new studies on Fmr1 knockout mice and mutant flies have begun to elucidate a key role for FMRP in synaptic growth, structure, and long-term plasticity.

Animals↗
PubMed2003

Plasticity in human sound localization induced by compressed spatial vision.

Auditory and visual target locations are encoded differently in the brain, but must be co-calibrated to maintain cross-sensory concordance. Mechanisms that adjust spatial calibration across modalities have been described (for example, prism adaptation in owls), though rudimentarily in humans. We quantified the adaptation of human sound localization in response to spatially compressed vision (0.5x lenses for 2-3 days). This induced a corresponding compression of auditory localization that was most pronounced for azimuth (minimal for elevation) and was restricted to the visual field of the lenses. Sound localization was also affected outside the field of visual-auditory interaction (shifted centrally, not compressed). These results suggest that spatially modified vision induces adaptive changes in adult human sound localization, including novel mechanisms that account for spatial compression. Findings are consistent with a model in which the central processing of sound location is encoded by recruitment rather than by a place code.

Acoustic Stimulation↗
PubMed2002

Insecticide-treated plastic tarpaulins for control of malaria vectors in refugee camps.

Spraying of canvas tents with residual pyrethroid insecticide is an established method of malaria vector control in tented refugee camps. In recent years, plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian shelter material for displaced populations in complex emergencies. Advances in technology enable polythene sheeting to be impregnated with pyrethroid during manufacture. The efficacy of such material against mosquitoes when erected as shelters under typical refugee camp conditions is unknown. Tests were undertaken with free-flying mosquitoes on entomological study platforms in an Afghan refugee camp to compare the insecticidal efficacy of plastic tarpaulin sprayed with deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin impregnated with deltamethrin (initially > or = 30 mg/m2) during manufacture, and a tent made from the factory impregnated tarpaulin material. Preliminary tests done in the laboratory with Anopheles stephensi Liston (Diptera: Culicidae) showed that 1-min exposure to factory-impregnated tarpaulins would give 100% mortality even after outdoor weathering in a temperate climate for 12 weeks. Outdoor platform tests with the erected materials (baited with human subjects) produced mosquito mortality rates between 86-100% for sprayed or factory-impregnated tarpaulins and tents (average approximately 40 anophelines and approximately 200 culicines/per platform/night), whereas control mortality (with untreated tarpaulin) was no more than 5%. Fewer than 20% of mosquitoes blood-fed on human subjects under either insecticide-treated or non-treated shelters. The tarpaulin shelter was a poor barrier to host-seeking mosquitoes and treatment with insecticide did not reduce the proportion blood-feeding. Even so, the deployment of insecticide-impregnated tarpaulins in refugee camps, if used by the majority of refugees, has the potential to control malaria by killing high proportions of mosquitoes and so reducing the average life expectancy of vectors (greatly reducing vectorial capacity), rather than by directly protecting refugees from mosquito bites. Mass coverage with deltamethrin-sprayed or impregnated tarpaulins or tents has strong potential for preventing malaria in displaced populations affected by conflict.

Afghanistan↗
PubMed1999

Eosinophils and neutrophils in biopsies from the middle ear of atopic children with otitis media with effusion.

OBJECTIVE AND DESIGN: The majority of patients with otitis media with effusion (OME) and atopy have been shown to have elevated levels of eosinophil cationic protein (ECP) in their middle ear fluid. The mechanism underlying these elevated levels of ECP is not clear. The purpose of this study was to investigate the feasibility of a quantitative determination of eosinophils and neutrophils in the middle ear lining by specific immunocytochemical markers, in order to study the extent of the involvement of these cells in patients with OME. METHODS: Bilateral middle ear biopsies from five children with persistent OME and atopy confirmed by in vitro testing were evaluated for the presence of eosinophils and neutrophils with monoclonal antibodies against specific granule proteins. Five subjects who had no signs of effusion or infection but were undergoing routine tympanoplasty for dry perforations served as controls. The biopsies were embedded in a plastic resin to improve the structural preservation of the target cells and to increase the resolution in the light microscope. Dual markers were used to determine which marker was better for eosinophils and neutrophils, respectively. The following markers were used: eosinophil cationic protein (EG2), and eosinophil peroxidase (EPO) for eosinophils and myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) for neutrophils. RESULTS: Antibodies against EPO gave a more localized and intense staining than antibodies against EG2. Antibodies against HNL appear more specific to neutrophils than antibodies against MPO that also recognize monocytes. The number of cells was determined both in the tissue and in the mucus covering the epithelium. Eosinophils and neutrophils were present in the subepithelial connective tissue and in the mucus blanket in the middle ear of patients with OME in significantly higher number than in the control group. In general, there were more inflammatory cells in the mucus than in the tissue itself, but the number of inflammatory cells in the mucus showed a significant positive correlation with the number of inflammatory cells in the tissue. There was a significant positive correlation between the number of neutrophils and the number of eosinophils in the tissue as well as in the mucus, irrespective of which marker was used. CONCLUSION: The results of this study show the feasibility of using specific antibodies to identify eosinophils and neutrophils in the middle ear. The initial data suggest that atopic children with OME have higher numbers of such cells as compared to non-OME controls.

Adolescent↗
PubMed2003

Acetaminophen modifies hippocampal synaptic plasticity via a presynaptic 5-HT2 receptor.

Acetaminophen (APAP) has recently been found to target COX-3, a newly identified COX isozyme. We discovered previously that selective COX-2 inhibitors reduce membrane excitability and long-term potentiation (LTP) in the hippocampus. The purpose of this study was to investigate whether APAP had effects on hippocampal LTP. We found that APAP reduced LTP induction and increased the paired-pulse facilitation (PPF). APAP-induced changes in LTP and PPF were blocked by a 5-hydroxytryptamine (serotonin, 5-HT(2/1)) receptor antagonist. The results suggest that APAP-induced modification of synaptic plasticity at hippocampal lateral perforant path-dentate granule cell synapses may be mediated by a presynaptic 5-HT(2) receptor.

Acetaminophen↗
PubMed2005

Differential vesicular targeting and time course of synaptic secretion of the mammalian neurotrophins.

Neurotrophins are a family of secreted neuronal survival and plasticity factors comprising NGF, BDNF, neurotrophin-3 (NT-3), and NT-4. Whereas synaptic secretion of BDNF has been described, the routes of intracellular targeting and secretion of NGF, NT-3, and NT-4 in neurons are poorly understood. To allow for a direct comparison of intracellular targeting and release properties, all four mammalian neurotrophins were expressed as green fluorescent protein fusion proteins in cultured rat hippocampal neurons. We show that BDNF and NT-3 are targeted more efficiently to dendritic secretory granules of the regulated pathway of secretion (BDNF, in 98% of cells; NT-3, 85%) than NGF (46%) and NT-4 (23%). For all NTs, the remaining cells showed targeting to the constitutive secretory pathway. Fusing the BDNF pre-pro sequence to NT-4 directed NT-4 more efficiently to the regulated pathway of secretion. All neurotrophins, once directed to the regulated secretion pathway, were detected near synapsin I-positive presynaptic terminals and colocalized with PSD-95-DsRed (postsynaptic density-95-Discosoma red), suggesting postsynaptic targeting of the neurotrophins to glutamatergic synapses. Depolarization-induced release of all neurotrophins from synaptic secretory granules was slow (delay in onset, 10-30 s; tau = 120-307 s) compared with transmitter release kinetics monitored with FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)hexatrienyl)pyridinium dibromide] destaining (onset, <5 s; tau = 13 +/- 2 s). Among the neurotrophins, NT-4 secretion was most rapid but still proceeded 10 times more slowly than transmitter secretion. Preincubation of neurons with monensin (neutralizing intragranular pH, thus solubilizing the peptide core) increased the speed of secretion of BDNF, NGF, and NT-3 to the value of NT-4. These data suggest that peptide core dissolution in secretory granules is the critical determinant of the speed of synaptic secretion of all mammalian NTs and that the speed of release is not compatible with fast transmitter-like actions of neurotrophins.

Animals↗
PubMed2002

Protein synthesis in the dendrite.

In neurons, many proteins that are involved in the transduction of synaptic activity and the expression of neural plasticity are specifically localized at synapses. How these proteins are targeted is not clearly understood. One mechanism is synaptic protein synthesis. According to this idea, messenger RNA (mRNA) translation from the polyribosomes that are observed at the synaptic regions provides a local source of synaptic proteins. Although an increasing number of mRNA species has been detected in the dendrite, information about the synaptic synthesis of specific proteins in a physiological context is still limited. The physiological function of synaptic synthesis of specific proteins in synaptogenesis and neural plasticity expression remains to be shown. Experiments aimed at understanding the mechanisms and functions f synaptic protein synthesis might provide important information about the molecular nature of neural plasticity.

Animals↗
PubMed2026

Altered Excitation-Inhibition Balance and mGluR1/5-Driven Plasticity in the Motor Cortical Surface in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by progressive dopaminergic degeneration and maladaptive motor cortical plasticity. However, the cellular pathways underlying cortical surface activity in the primary motor cortex (M1) remain unclear, despite serving as a potential target for electrotherapy. We investigated the excitatory-inhibitory (E-I) balance and synaptic plasticity of superficial M1 circuits in a unilateral 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Using extracellular local field potential and whole-cell patch recordings from the contralateral and ipsilateral M1 hemispheres of hemi-parkinsonian rats, we observed a significantly elevated field excitatory postsynaptic potential (fEPSP) input-output function but unchanged intrinsic neuronal excitability in the M1 superficial layer. An altered relative contribution between alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated transmission was reflected by a significantly increased AMPA/NMDA ratio. Markedly reduced inhibitory synaptic tone was also evidenced by the decreased amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), supporting an E-I imbalance favoring excitation in PD. Furthermore, group I metabotropic glutamate receptor (mGluR1/5)-dependent long-term depression (LTD) was abolished in the ipsilateral PD hemisphere, whereas NMDAR-dependent LTD remained intact. In summary, dopamine depletion appears to enhance network excitation and disrupt mGluR1/5-mediated control of M1 surface circuitry. Our findings identify altered cortical surface mGluR-dependent plasticity in the hemi-parkinsonian model; however, the relationship between these electrophysiological alterations and individual motor outcomes remains to be determined.

Animals↗
PubMed2004

Drugs for stroke recovery: the example of amphetamines.

Clinical trials of pharmacological agents in stroke have mainly focused on events that need to be modified in the very acute stage, such as restoration of blood flow with thrombolytic therapy or reducing the effects of ischaemia with neuroprotective therapy. Thrombolytic therapy is, however, only effective within the first few hours of stroke onset and so far, no neuroprotective therapy has proven to be efficacious in humans. Thus, there is a great need for new pharmacological strategies to improve outcome after stroke. Accumulating evidence supports the assumption that the brain is plastic and improvements can be expected after permanent injuries. Acute and chronic alterations in neurotransmitter regulation after injury affects plasticity and may thus provide a basis for new pharmacological targets for stroke recovery. The search for pharmacological therapies that affect the recovery process after a permanent injury has been intensified during the last decade. Amphetamines, in combination with training, are currently one of the most promising pharmacological strategies studied for recovery after stroke. Several non-mutually exclusive hypotheses, more or less supported by experimental studies, have tried to explain the mechanisms underlying the facilitation of recovery of function with amphetamine treatment. Amphetamines are believed to hasten the processes in the brain, such as plasticity mechanisms and resolution of diaschisis. The combination of amphetamine and task-specific training seems to be of importance to the outcome. Results from animal studies are consistent between different models and species, and mainly show an increased rate of recovery but there are a few exceptions, with some studies reporting no effect or even a decreased recovery rate. In humans the number of randomised controlled studies of amphetamines is growing rapidly. Results from a Cochrane systematic review indicate a faster motor and language recovery rate with treatment, but the number of studies is too few and studies are too small to draw definite conclusions about the effect on recovery of stroke. Data in the systematic review also indicate that the mortality rate is higher in amphetamine-treated patients compared with placebo-treated patients. However, this is most likely because of baseline imbalances between the treatment groups with patients with more severe strokes being allocated to amphetamine treatment. Further clinical trials are justified, but at present amphetamines should not be used in clinical practice.

Amphetamines↗
PubMed2005

Evolution of phenotypic plasticity: where are we going now?

The study of phenotypic plasticity has progressed significantly over the past few decades. We have moved from variation for plasticity being considered as a nuisance in evolutionary studies to it being the primary target of investigations that use an array of methods, including quantitative and molecular genetics, as well as of several approaches that model the evolution of plastic responses. Here, I consider some of the major aspects of research on phenotypic plasticity, assessing where progress has been made and where additional effort is required. I suggest that some areas of research, such the study of the quantitative genetic underpinning of plasticity, have been either settled in broad outline or superseded by new approaches and questions. Other issues, such as the costs of plasticity are currently at the forefront of research in this field, and are likely to be areas of major future development.

Journal Article↗
PubMed2004

Redirected primary T cells harboring a chimeric receptor require costimulation for their antigen-specific activation.

Chimeric receptor (CR)-redirected lymphocytes (T bodies) have great potential in the eradication of tumor cells. To extend this approach to target cells that do not express surface ligands to costimulatory receptors (eg, cancer cells), we have generated an antibody-based tripartite chimeric receptor (TPCR) that contains scFv linked to the costimulatory molecule, CD28 without its ligand-binding domain, and to the cytoplasmic moiety of the FcRgamma subunit. In this study, we tested the ability of 2,4,6-trinitrophenyl (TNP)-specific TPCR to drive primary, naive T cells derived from CR-transgenic (Tg) mice to undergo full activation. As a control, we used Tg mice expressing a similar transgene but lacking the signaling region of CD28 (Tg-TPCRDeltaCD28). Only T cells from the TPCR-Tg and not the CD28-truncated TPCR-Tg mice could undergo activation following stimulation on hapten-modified target cells not expressing B7. Moreover, when stimulated with TNP protein displayed on plastic, the TPCR-Tg T cells expressing the entire TPCR gene became fully activated for proliferation, interleukin 2 production, protection from apoptosis, and killing of TNP-modified target cells. Finally, TPCR-Tg mice manifested a delayed-type hypersensitivity response following skin challenge in the absence of priming. Taken together, our results suggest that the TPCR is the receptor configuration of choice for clinical applications using primary T or stem cells.

Animals↗
PubMed1992

Inhibition of cell adhesion to plastic substratum by phosphorothioate oligonucleotide.

Antisense oligonucleotides have been widely used to achieve specific inhibition of targeted gene expression. However, the mechanism of action is not well understood and in many systems sequence-independent effects occur. We have recently shown that chronic administration of an antisense c-myc phosphorothioate oligonucleotide can specifically inhibit expression of the c-myc protein and growth in human breast cancer cells. We now identify an additional effect of the same oligonucleotide on cell adhesion. Transient delivery through electroporation of 2.5 microM antisense-myc oligonucleotide to MCF-7 cells results in 85% inhibition of adhesion to plastic substratum within 24 h. Both the onset of this effect and the subsequent recovery occur without a change in cell viability, growth, or alteration of adhesion to Matrigel, collagen IV, laminin, or fibronectin. However, no parallel changes in c-myc mRNA or protein expression are detectable, suggesting that in this instance inhibition of adhesion caused by antisense-myc oligonucleotide may involve a mechanism independent of the target sequence.

Base Sequence↗
PubMed1995

Long-term sensory hyperinnervation following neonatal skin wounds.

Skin innervation during wound healing was investigated using immunocytochemical staining with the panneuronal marker antiprotein gene product (PGP) 9.5, which labels the entire innervation of the skin throughout development and in the adult. Full-thickness skin wounds in the hairy skin of the foot in neonatal rats result in pronounced hyperinnervation of the tissue that persists long after the wound has healed (at least 12 weeks). Quantification of this hyperinnervation by image analysis indicates that skin innervation density in the wounded area can increase up to 300%. The effect is greatest when wounds are performed at postnatal day (P) 0 or 7, declining when performed at P14 and P21 to resemble the weaker and transient effect in the adult. Staining with selective markers for different neuronal populations innervating skin (monoclonal anti-RT97 staining the myelinated axons of large light sensory ganglion cells; anticalcitonin gene-related peptide staining unmyelinated C axons, thinly myelinated A delta axons, and a subpopulation of large A fibres) reveal that both A- and C-fibre sensory axons contribute to this response. Destruction of the majority of the C-fibre population with neonatal capsaicin pretreatment, which leaves large A fibres intact, significantly reduces the hyperinnervation response at 14 days, confirming a major contribution from both A and C fibres. Sympathetic axons, stained with anti-tyrosine hydroxylase, do not sprout into the wounded area. Furthermore, pretreatment of neonates with 6-hydroxydopamine, which destroys the sympathetic innervation, does not significantly reduce the overall sprouting response, as identified by anti-PGP9.5 staining. Behavioural sensory testing revealed a 50% drop in the mechanical threshold in the wounded area after 3 weeks. These remarkably long-term and specific effects on sensory terminal axons following neonatal skin wounding indicate the plasticity of cutaneous innervation density following alterations in the target tissue at a critical stage of development.

Aging↗