Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Target plasticity”

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 145 records · Page 8Linked to original sources
PubMed1989

Cultured brain endothelium inhibits the cytocidal action of natural killer cells on glioma.

The killing of GL26 and YAC-1 cells by natural killer cells (NKC) is reduced in the presence of a monolayer of endothelial cells. This reduction in cytotoxicity correlates with the degree of adhesion between the tumor cells and the endothelial monolayers. The cytotoxicity of NKC toward glioma was 10% when carried out on plastic, but a monolayer of endothelium derived from brain inhibited the cytotoxicity by about 90%. Endothelium from thoracic duct and lung also inhibited cytotoxicity by about 90%, endothelium from aorta inhibited by 55% and that from ovary by only 45%. Cytotoxicity of NKC toward YAC-1 (a control NK target) was 40% on plastic, but a monolayer of endothelium from thoracic duct inhibited the cytotoxicity by 75%. Endothelium from brain and lung inhibited cytotoxicity by about 60%, aorta by 50%, and ovary by 40%. Interactions between tumor cells and the host-organ microvascular endothelium appear to protect neoplastic cells from natural surveillance mechanisms and may play a role in the formation of metastatic tumor deposits.

Animals↗
PubMed2006

Target-specific regulation of synaptic efficacy in the feeding central pattern generator of Aplysia: potential substrates for behavioral plasticity?

The contributions to this symposium are unified by their focus on the role of synaptic plasticity in sensorimotor learning. Synaptic plasticities are also known to operate within the central pattern generator (CPG) circuits that produce repetitive motor programs, where their relation to adaptive behavior is less well understood. This study examined divergent synaptic plasticity in the signaling of an influential interneuron, B20, located within the CPG that controls consummatory feeding-related behaviors in Aplysia. Previously, B20 was shown to contain markers for catecholamines and GABA (Díaz-Ríos et al., 2002), and its rapid synaptic signaling to two follower motor neurons, B16 and B8, was found to be mediated by dopamine (Díaz-Ríos and Miller, 2005). In this investigation, two incremental forms of increased synaptic efficacy, facilitation and summation, were both greater in the signaling from B20 to B8 than in the signaling from B20 to B16. Manipulation of the membrane potentials of the two postsynaptic motor neurons did not affect facilitation of excitatory postsynaptic potentials (EPSPs) to either follower cell. Striking levels of summation in B8, however, were eliminated at hyperpolarized membrane potentials and could be attributed to distinctive membrane properties of this postsynaptic cell. GABA and the GABAB agonist baclofen increased facilitation and summation of EPSPs from B20 to B8, but not to B16. The enhanced facilitation was not affected when the membrane potential of B8 was pre-set to hyperpolarized levels, but GABAergic effects on summation were eliminated by this manipulation. These observations demonstrate a target-specific amplification of synaptic efficacy that can contribute to channeling the flow of divergent information from an intrinsic interneuron within the buccal CPG. They further suggest that GABA, acting as a cotransmitter in B20, could induce coordinated and target-specific pre- and postsynaptic modulation of these signals. Finally, we speculate that target-specific plasticity and its modulation could be efficient, specific, and flexible substrates for learning-related modifications of CPG function.

Animals↗
PubMed2005

Astrocytes as targets for neuroprotective drugs.

Astrocytes have long been considered as merely structural support for neurons in the central nervous system (CNS). However, more recent evidence has demonstrated roles for astrocytes in both neuroprotection and neurodegeneration. One major role is in the modulation of glutamatergic neurotransmission. Astrocytes can also modulate inflammatory responses in the CNS; they contain high levels of antioxidants and mediate neuronal protection after physiological assault, as well as releasing neurotrophic factors and being important to neuronal plasticity in the hippocampus. Targeting astrocytes as mediators for neuroprotective drugs may be a promising strategy.

Animals↗
PubMed2004

Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: nicotine and chlorpyrifos.

Alpha7 nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore potential targets for developmental neurotoxicants. We administered nicotine to neonatal rats during discrete periods spanning the onset and peak of axonogenesis/synaptogenesis, focusing on three brain regions with disparate distributions of cell bodies and neural projections: brainstem, forebrain and cerebellum. Nicotine treatment on postnatal days (PN) 1-4 had little or no effect on alpha7 nAChRs but treatment during the second (PN11-14) or third (PN21-24) weeks elicited significant decrements in receptor expression in brainstem and cerebellum, regions containing cell bodies that project to the forebrain. Exposure to chlorpyrifos, a neurotoxicant pesticide that acts partially through cholinergic mechanisms, also elicited deficits in alpha7 nAChRs during the second postnatal week but not the first week. For both nicotine and chlorpyrifos, the effects on alpha7 nAChRs were distinct from those on the alpha4beta2 subtype. Continuous prenatal nicotine exposure, which elicits subsequent, postnatal deficits in axonogenesis and synaptogenesis, also produced delayed-onset changes in alpha7 nAChRs, characterized by reductions in the forebrain and upregulation in the brainstem and cerebellum, a pattern consistent with impaired axonogenesis/synaptogenesis and reactive sprouting. Males were more sensitive to the persistent effects of prenatal nicotine exposure on alpha7 nAChRs, a pattern that mimics neurobehavioral deficits resulting from this treatment. The present findings reinforce the mechanistic involvement of alpha7 nAChRs in the actions of developmental neurotoxicants, and its biomarker potential for neuroteratogens that target neuritic outgrowth.

Acetylcholine↗
PubMed2003

Neonatal depletion of serotonin increases the numbers of callosally projecting neurons in cat visual areas 17 and 18.

We investigated the influence of neonatal depletion of serotonin on the developmental reduction of callosal connections in cat visual cortex. Neonatal kittens were injected with 5,7-dihydroxytryptamine. At the age of 3 months, Fast Blue was injected into visual areas of one hemisphere in these and control cats and retrogradely labeled perikarya were mapped in the opposite hemisphere. In both groups callosally projecting neurons were found in a 3-5 mm wide belt centered on the transient zone of areas 17 and 18. However, numbers of labeled neurons were twice higher in the serotonin-depleted cats. We postulate that normally serotonin intensifies the process of axon pruning by augmenting developmental plasticity, therefore its depletion reduced the plasticity and more axons targeting callosal zones were stabilized, even though ectopic projections were still eliminated.

5,7-Dihydroxytryptamine↗
PubMed1997

Modifiable neuronal connections: an overview for psychiatrists.

Synaptic plasticity is currently the target of much neurobiological research, because it is thought to play an important role in brain function (particularly memory formation). However, it has attracted little attention from psychiatrists to date despite accumulating evidence that links it to various clinical syndromes, including amnesia and possibly psychosis. The purpose of this article is to present an overview of the two major arms of synaptic plasticity research-theoretical (the field of neural network modeling) and neurobiological (long-term potentiation). Artificial neural networks are a class of theoretical model that has been developed with the aim of understanding how information could, in principle, be represented by large numbers of interconnected and relatively simple units. Over the past few decades, several theoretical accounts of information-processing mechanisms have been developed, and these are briefly reviewed. The principle common to representation formation in nearly all neural networks is that of "associability"-the idea that streams of information are combined by forming, strengthening, or pruning connections between them to form new representations that can later be retrieved. Associability also lies at the heart of psychological theories of information storage in the brain. Research into associability has directed the attention of many experimenters toward the possible biological correlates of such mechanisms. Of particular interest is the recent discovery that some neurons appear to possess connections of modifiable strength. The implications of this finding for psychiatry are discussed in relation to representational disorders such as delusions and amnesia.

Amnesia↗
PubMed1995

Collateral sprouting and responsiveness to nerve growth factor of ageing neurons.

Loss of neuronal plasticity and/or alterations in neuronal targets with ageing can induce degenerative phenomena in the nervous system. To study the possible contribution of reduced neuronal plasticity to age-related neurodegeneration, we examined the sprouting response to aged rat iridial nerves on in oculo grafts of peripheral tissues taken from young and old animals. Contrary to previous observations in young hosts, both young and old transplants became re-innervated by host nerves to a similar extent, with a nerve density which was typical of old target tissue in situ. Nerve growth factor treatment increased the innervation density on all transplants. However, the increase was significant only on young target tissues.

Aging↗
PubMed1996

The Drosophila tumor suppressor gene, dlg, is involved in structural plasticity at a glutamatergic synapse.

BACKGROUND: Synaptic contacts between neurons and their targets are dynamic entities that can change depending on developmental and functional states of the pre- and postsynaptic cell. However, the molecular factors involved in this plasticity have remained largely unknown. We have demonstrated previously that the Drosophila tumor suppressor gene, discs-large (dlg), is expressed at neuromuscular synapses, and is required for normal synapse structure. A family of dlg homologues is also expressed at mammalian synapses, where they interact with the N-methyl-D-aspartate receptor and ion channels. Here, we provide the first demonstration of the involvement of dlg in structural synaptic plasticity during postsynaptic target growth. RESULTS: We used a temperature-sensitive dlg allele to demonstrate that there are two stages, late embryogenesis and larval stages, at which dlg is necessary for normal formation of synapses. These stages are coincident with dynamic DLG expression at presynaptic sites in the late embryo, and at postsynaptic regions in the larva. Ultrastructural and confocal analyses reveal that Drosophila neuromuscular junctions undergo a dramatic expansion of the postsynaptic apparatus, which is paralleled by target muscle growth. We show that this process of postsynaptic expansion is partially blocked in dlg mutants. CONCLUSIONS: Our results demonstrate that dlg is required during synapse maturation. We show that dlg is involved in the determination of postsynaptic size during target muscle growth. Because motoneuron targets in the larva are continuously growing, synaptic contacts are structurally plastic, undergoing continuous expansion. We conclude that dlg plays an important role in this form of structural synaptic plasticity.

Animals↗
PubMed2004

Modulation of associative human motor cortical plasticity by attention.

The role of attention in generating motor memories remains controversial principally because it is difficult to separate the effects of attention from changes in kinematics of motor performance. We attempted to disentangle attention from performance effects by varying attention while plasticity was induced in human primary motor cortex by external stimulation in the absence of voluntary movement. A paired associative stimulation (PAS) protocol was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single-pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the right abductor pollicis brevis muscle (APB) to generate near-synchronous events in the left primary motor cortex. In experiment 1, the spatial location of attention was varied. PAS failed to induce plasticity when the subject's attention was directed to their left hand, away from the right target hand the cortical representation of which was being stimulated by PAS. In experiment 2, the grade of attention to the target hand was manipulated. PAS-induced plasticity was maximal when the subject viewed their target hand, and its magnitude was slightly reduced when the subject could only feel their hand. Conversely, plasticity was completely blocked when the subject's attention was diverted from the target hand by a competing cognitive task. A similar modulation by attention was observed for PAS-induced changes in the duration of the silent period evoked by TMS in voluntarily contracted muscle. Associative plasticity in the human motor cortex depends decisively on attention.

Adult↗
PubMed1997

Pathway-specific synaptic plasticity: activity-dependent enhancement and suppression of long-term heterosynaptic facilitation at converging inputs on a single target.

To explore mechanisms of long-term, pathway-specific synaptic plasticity, we examined consequences of differential stimulation of Aplysia sensorimotor connections in culture where two sensory neuron (SN) inputs converge on a single target motor cell L7. A single pairing of tetanus in one SN with bath application of 5-HT evoked long-term (24 hr) increase in efficacy of the SN connection given paired stimulation that was comparable in magnitude to the increase in synaptic efficacy evoked with repeated applications of 5-HT. Repeated pairing of tetanus in one SN with applications of 5-HT evoked a significant increase in efficacy of the SN connection given paired stimuli, and significant reduction in facilitation that is normally evoked by repeated applications of 5-HT in the unpaired SN connection. Hyperpolarization of L7 or incubation with APV interfered with both enhancement of facilitation with paired stimulation and suppression of facilitation with unpaired stimulation, but without interfering with long-term facilitation evoked either by repeated applications of 5-HT or by a single pairing. The results suggest that a single connection can undergo at least two forms of activity-dependent, pathway-specific facilitation lasting more than 24 hr. One form, evoked with a single pairing, is initiated and maintained primarily by activity in the presynaptic neuron. The other form, evoked with repeated paired stimuli, requires target-dependent activity that differentially modulates long-term heterosynaptic facilitation at the converging inputs.

2-Amino-5-phosphonovalerate↗
PubMed1978

Cell-mediated destruction of cells grown on artificial capillaries.

This investigation was designed to determine the conditions required to assess cell-mediated destruction of target L-cells grown on artificial capillaries. In control cultures that contained L-cells alone, solid nodules with a diameter of 1 mm as well as dense cellular growth could be visually observed by the 12th day of culture. Alloimmune spleen cells from both immunized and normal C57BL/10 mice were shown to be capable of destroying tritiated thymidine-labeled L-cells growing on artificial capillaries. The destruction of target cells grown as monolayers in capillary culture correlated well with monolayer cultures incubated in 16-mm plastic tissue culture wells. When target cells were grown in capillary culture for 5 days before the addition of effector cells, significant destruction by normal effector cells was not observed until the 15th day of culture whereas that mediated by immune cells was observed by the 7th day. The possible effects of cell-culturing conditions on the kinetics of cell-mediated destruction in capillary chambers are discussed.

Animals↗
PubMed2004

Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor.

A diet high in total fat (HF) reduces hippocampal levels of brain-derived neurotrophic factor (BDNF), a crucial modulator of synaptic plasticity, and a predictor of learning efficacy. We have evaluated the capacity of voluntary exercise to interact with the effects of diet at the molecular level. Animal groups were exposed to the HF diet for 2 months with and without access to voluntary wheel running. Exercise reversed the decrease in BDNF and its downstream effectors on plasticity such as synapsin I, a molecule with a key role in the modulation of neurotransmitter release by BDNF, and the transcription factor cyclic AMP response element binding protein (CREB), important for learning and memory. Furthermore, we found that exercise influenced the activational state of synapsin as well as of CREB, by increasing the phosphorylation of these molecules. In addition, exercise prevented the deficit in spatial learning induced by the diet, tested in the Morris water maze. Furthermore, levels of reactive oxygen species increased by the effects of the diet were decreased by exercise. Results indicate that exercise interacts with the same molecular systems disrupted by the HF diet, reversing their effects on neural function. Reactive oxygen species, and BDNF in conjunction with its downstream effectors on synaptic and neuronal plasticity, are common molecular targets for the action of the diet and exercise. Results unveil a possible molecular mechanism by which lifestyle factors can interact at a molecular level, and provide information for potential therapeutic applications to decrease the risk imposed by certain lifestyles.

Animals↗
PubMed2006

Automatic drive of limb motor plasticity.

The ability to perform accurate limb movements may require learning mechanisms that continually tune the motor system. In the current study, we isolate a form of pure limb motor plasticity. Participants reached to targets that were turned off just after the onset of an initial eye movement, reappearing at a new location at the end of the reaching movement. In contrast to classical prism or virtual reality paradigms, our task eliminated sensory adaptation by always maintaining a congruency between the seen and felt limb position. We also minimized awareness and potential adaptation processes on the basis of volitional strategies by progressively increasing the size of the target perturbations. In this manner, our adaptation procedure mimicked conditions used to study saccadic adaptation. The results indicated that adaptation under these conditions led to a robust after-effect that generalized to a large range of movements within the workspace. This fully natural, nonimposed generalization of adaptation is not expressed in a spatial coordinate system, but more likely in a joint-centered coordinate space.

Adaptation, Psychological↗
PubMed1984

Cell-mediated cytotoxicity to autologous hepatocytes in HBsAg positive liver disease: an analysis of the killing specificity and of the clinical use of the test.

The specificity of a system measuring cell-mediated cytotoxicity as effector-induced target cell detachment from plastic recently adopted to study autologous hepatocyte killing in liver disease, was examined in 17 HBsAg positive liver patients whose hepatocytes (after biopsy digestion with collagenase) were incubated in Terasaki plates with the corresponding blood lymphocytes over two days. The hepatocyte viability and the specificity of the effectors were evaluated as determinants of the clinical value of the test. We found that: (a) hepatocytes in all experiments showed membrane damage owing to the lytic action of collagenase on the small liver core; (b) patients' lymphocytes detached diseased autologous hepatocytes more efficiently than did normal lymphocytes with healthy hepatocytes; (c) in eight patients cytotoxicity appeared equally distributed between a population enriched in T cells and one enriched in non-T cells; yet the mean cytotoxic index of the latter subset was higher than that of the former; (d) cytotoxicity was not blocked by the addition of either aggregated IgG or purified HBsAg; (e) protein synthesis seemed required to promote hepatocyte detachment, for lymphocytes treated with Actinomycin D were no longer active. Poor target viability detracts from the specificity and the clinical value of the test, that therefore turns out to be a major problem of liver cell culture.

Adolescent↗
PubMed2026

ATP-Dependent Chromatin Remodelers in Prostate Cancer Progression and Therapeutic Resistance.

ATP-dependent chromatin remodelers (ACRs) have emerged as central determinants of prostate cancer (PCa) progression and therapy resistance. Organized into four mechanistically distinct families (SWI/SNF, ISWI, CHD, and INO80/SWR), ACRs govern nucleosome positioning genome-wide and thereby occupy a central position in the epigenomic regulatory landscape that dictates where and when transcription factors, including the androgen receptor (AR), can engage chromatin. This review discusses ACR dysregulation in PCa through both mutational and non-mutational mechanisms. These are illustrated by discussing how the functional consequences are highly context-dependent, varying with disease stage, prior treatment exposure, and tumor ancestry. Loss of the tumor suppressors RB1, TP53, and PTEN each generates specific ACR dependencies that are potentially therapeutically exploitable, including synthetic lethal relationships between PTEN deficiency and SWI/SNF ATPase activity. Across the spectrum of AR signaling states, from hormone-sensitive disease through therapy-resistant neuroendocrine and double-negative PCa subtypes, ACR complex composition and genomic targeting are continuously reprogrammed to enable and sustain lineage plasticity and endocrine therapy escape. Therapeutic strategies targeting SWI/SNF, ISWI, and INO80/SWR complexes are at varying stages of preclinical and clinical development and are attractive novel avenues to target therapy resistant PCa.

ATP dependent chromatin remodeling↗
PubMed1978

Expression of oncofetal antigens on murine sarcomas characterized for expression of endogenous MuLV.

A rabbit antiserum raised by repeated immunization with BALB/c fetuses obtained at 10-14 days of gestation was used to search for oncofetal antigens (OFA) in murine sarcomas which had previously been characterized for the expression of endogenous murine leukemia virus (MuLV). Iodinated protein A from staphylococcus aureus (IPA) was used to quantitate binding of the antiserum to cultured tumor or fetal cells or to saline extracts of tumors and fetuses. Use of the "antigen" extracts facilitated the assay: the extracts bound to plastic and served as targets for the binding assay, eliminating the need to establish tumors in culture. After absorbtion in vitro and in vivo with adult tissues the rabbit antiserum bound to day 10-14 fetal cells and extract but not to endogenous MuLV (BALB virus 1). The antiserum bound equally well to MuLV-negative and MuLV-positive sublines of MCA-induced sarcomas 1420 and 1414 but not to Moloney sarcoma cells and MCA-induced sarcoma 1386. Thus, the absorbed antiserum detects a class of common cross-reacting antigens which are serologically distinct from MuLV-associated antigens.

Animals↗
PubMed1994

The search for novel microbial fine chemicals, agrochemicals and biopharmaceuticals.

An ever-increasing number of fine chemicals and enzymes is now produced based on microbial biotechnology. Microbial products generally display desired chirality, are biodegradable and are produced from renewable (agro)-substrates. Bioconversion reactions, based on the use of (immobilised) biocatalysts (cell or enzymes), yield interesting regio- and enantioselective molecules under mild reaction conditions, starting from racemic precursors. Furthermore these bioprocesses have a positive environmental impact. Ingenious screening procedures for novel microbial primary and secondary metabolites, bioactive peptides, proteins and enzymes reveal that only the tip of the iceberg has been explored. Examples of such novel microbial products pertain to enzymes, enzyme-inhibitors, biopolysaccharides, bio-plastics, bioactive peptides, bacteriocins, targeted toxins, alkaloids, steroids, immunomodulators, vaccines, antibiotics and lantibiotics, biopesticides, vitamins and related growth factors, amino acids and specialty sugars, polyols and organic acids, biomagnets, bioflavours and biopigments. Several trends are discussed which are now in vogue to detect novel useful compounds from microbes. Examples are given of those microbial metabolites and enzymes, which have attracted industrial interest.

Amino Acid Sequence↗
PubMed2004

Administration of nicotine to adolescent rats evokes regionally selective upregulation of CNS alpha 7 nicotinic acetylcholine receptors.

Alpha 7 Nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore targets for developmental neurotoxicants. We administered nicotine to adolescent rats and evaluated the effects on alpha 7 nAChRs in the striatum, brainstem and cerebellum. During the period of nicotine administration (30-47.5 days of age), nicotine elicited alpha 7 nAChR upregulation with a regional hierarchy of striatum>brainstem>cerebellum. Values returned to normal or became slightly subnormal almost immediately after the cessation of treatment (50 days of age) with no further changes through 75 days of age. The temporal and regional patterns of the effects on alpha 7 nAChRs were distinct from those reported earlier for the alpha 4 beta 2 subtype, and neither adult nor fetal/neonatal administration upregulates the alpha 7 subtype in the striatum. Targeting of the striatum is thus unique to nicotine exposure during adolescence and parallels earlier work showing regionally selective effects of this treatment on synaptic signaling. We obtained preliminary evidence for nicotine-induced oxidative stress as a potential contributory mechanism. The present findings reinforce the concept of biologically distinct effects of nicotine in the adolescent brain and provide evidence for a mechanistic involvement of alpha 7 nAChRs in its unique effects during this developmental period.

Age Factors↗