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Stability of synaptic plasticity in the adult rat visual cortex induced by complex environment exposure.

Studies have demonstrated the effects of complex environment (EC) housing on brain plasticity both during postnatal development and in adulthood, but it is not clear how long these plastic changes persist nor what happens when environmental exposure is discontinued. Here we examined layer IV in the visual cortex of adult male rats for the: (1) effects of EC housing on synaptic plasticity, and (2) persistence of the synaptic changes after withdrawal from the complex environment. Fifty-eight adult male Long Evans rats were assigned to either: EC, socially paired housing (SC), or individual housing (IC). These rats remained in their assigned environment for 30 days. After 30 days, all rats in SC and some animals from the EC and IC groups were removed and perfused. The remaining animals in EC were then assigned to either remain in EC (ECEC) or be subsequently housed in IC (ECIC) for another 30 days. Similarly, rats in the IC group either remained in IC (ICIC) or were subsequently housed in EC (ICEC) for another 30 days. Electron microscopy results showed that all rats exposed to EC had significantly more synapses/neuron compared to SC, IC, and ICIC animals. Longer exposure to EC (ECEC) did not result in statistically more synapses per neuron; however, decreased neuron volume was seen. EC-induced synaptic changes persisted for an additional 30 days after withdrawal from EC (ECIC) confirming that EC-induced plastic changes occur in the brain regardless of age and indicating that once changes occur they tend to persist.

Animals↗

Dendritic spine plasticity: looking beyond development.

Most excitatory synapses in the CNS form on dendritic spines, tiny protrusions from the dendrites of excitatory neurons. As such, spines are likely loci of synaptic plasticity. Spines are dynamic structures, but the functional consequences of dynamic changes in these structures in the mature brain are unclear. Changes in spine density, morphology, and motility have been shown to occur with paradigms that induce synaptic plasticity, as well as altered sensory experience and neuronal activity. These changes potentially lead to an alteration in synaptic connectivity and strength between neuronal partners, affecting the efficacy of synaptic communication. Here, we review the formation and modification of excitatory synapses on dendritic spines as it relates to plasticity in the central nervous system after the initial phase of synaptogenesis. We will also discuss some of the molecular links that have been implicated in both synaptic plasticity and the regulation of spine morphology.

Animals↗

Short-term plasticity in excitatory synapses of the rat medial preoptic nucleus.

The medial preoptic nucleus (MPN) regulates sexual behavior which is subject to experience-dependent modifications. Such modifications must depend on functional plasticity in the controlling neural circuits. Thus, MPN synapses are likely candidates for the site of alterations. The present work is a first systematic study of functional synaptic plasticity at glutamatergic synapses in the MPN. Short-term activity-dependent plasticity was investigated using a slice preparation from young male rats. The average efficacy of AMPA/kainate-receptor-mediated synaptic transmission was activity-dependent, showing a peak at a steady stimulation rate of 2 Hz. The variation in efficacy was attributed to mainly presynaptic factors since the average response amplitude was roughly paralleled by the response probability. Upon paired-pulse stimulation, paired-pulse facilitation as well as paired-pulse depression was observed. In some cases, paired-pulse facilitation as well as paired-pulse depression was recorded from an individual neuron depending on the interval between the paired stimuli. On average, paired-pulse facilitation was observed at intervals <500 ms, and paired-pulse depression at intervals in the range 1-4 s. The findings thus reveal complex activity-dependent short-term plasticity of the functional synaptic properties in the medial preoptic nucleus.

Animals↗

Rapid and long-term plasticity in the neonatal and adult retinotectal pathways following a retinal lesion.

The uncrossed retinotectal projection restricts its terminal fields to the ventral boundary of the visual layers at the rostral tectum during early post natal development. During this critical period, temporal retinal lesions in one eye induce laminar rearrangements in the uncrossed pathway of the intact eye toward the collicular surface previously occupied, almost exclusively, by the crossed retinal axon population. We have compared, using anterograde tracing techniques, the time course and magnitude of the axonal sprouting resulting from retinal lesions in neonates and adults. Early retinal lesions (within the first two post natal weeks) induced extensive and rapid plasticity of the ipsilateral projection 48 h after the lesions. On the third post natal week, similar retinal lesions induced a small reorganization of the intact eye's uncrossed projection within a 3-week survival time. Nevertheless, giving the animals a long-term survival, resulted in an increased plastic capability, suggesting that even after the critical period, intact retinal axons can respond efficiently to injury. The results suggest two phases of axonal reorganization within this subcortical pathway: a rapid plasticity within the critical period and a slow, but continuous plasticity in adulthood.

Age Factors↗

Interaction of metabolites with R. rhodochrous during the biodegradation of di-ester plasticizers.

The commonly used plasticizers di-ethylhexyl phthalate (DEHP) and di-ethylhexyl adipate (DEHA) are known to partially degrade in the presence of soil microorganisms, such as Rhodococcus rhodochrous, releasing persistent and toxic metabolites. The metabolites adipic acid and 2-ethylhexanol were both shown to inhibit growth of the degrading microbe. 2-Ethylhexanol enhanced the activity of ethanol dehydrogenase - an enzyme involved in its metabolism - but the activity of this enzyme was inhibited by adipic acid. The metabolite usually seen in the highest concentrations - 2-ethylhexanoic acid - did not exhibit any evidence of inhibition. It was shown that the high concentration of this metabolite was due to the inability of R. rhodochrous to degrade it. Comparisons with other small carboxylic acids supported the argument that the ethyl branch was the reason for the resistance of 2-ethylhexanoic acid to degradation. The hydrophobicity of the cell surface was shown to be a factor in plasticizer degradation. The primary carbon source could be either water-soluble or hydrophobic and a hydrophobic substrate led to a cell surface that attracted the plasticizer and facilitated degradation. The most hydrophobic of the plasticizers, DEHP, was particularly sensitive to this effect.

Adipates↗

RNA binding proteins and the regulation of neuronal synaptic plasticity.

Cognitive function and memory rely on synaptic plasticity - the ability of synapses to modify their strength in response to stimulation. Emerging evidence indicates that post-transcriptional gene regulation is necessary for synaptic plasticity at several levels: by increasing proteome diversity through alternative splicing, or by enabling activity-dependent regulation of mRNA localization, translation or degradation in the dendrite. Mouse knockout studies have linked three RNA-binding proteins, fragile X mental retardation protein, cytoplasmic polyadenylation element binding factor and neuro-oncological ventral antigen to specific aspects of synaptic plasticity. Specificity in the regulation of synaptic plasticity might, in part, relate to the functional coherence of proteins encoded by the RNA targets of each RNA-binding protein.

Alternative Splicing↗

Lifelong learning: ocular dominance plasticity in mouse visual cortex.

Ocular dominance plasticity has long served as a successful model for examining how cortical circuits are shaped by experience. In this paradigm, altered retinal activity caused by unilateral eye-lid closure leads to dramatic shifts in the binocular response properties of neurons in the visual cortex. Much of the recent progress in identifying the cellular and molecular mechanisms underlying ocular dominance plasticity has been achieved by using the mouse as a model system. In this species, monocular deprivation initiated in adulthood also causes robust ocular dominance shifts. Research on ocular dominance plasticity in the mouse is starting to provide insight into which factors mediate and influence cortical plasticity in juvenile and adult animals.

Animals↗

Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice.

BACKGROUND: Advancing age is typically accompanied by deficits in learning and memory. These deficits occur independently of overt pathology and are often considered to be a part of "normal aging." At the neuronal level, normal aging is known to be associated with numerous cellular and molecular changes, which include a pronounced decrease in neuronal excitability and an altered induction in the threshold for synaptic plasticity. Because both of these mechanisms (neuronal excitability and synaptic plasticity) have been implicated as putative cellular substrates for learning and memory, it is reasonable to propose that age-related changes in these mechanisms may contribute to the general cognitive decline that occurs during aging. RESULTS: To further investigate the relationship between aging, learning and memory, neuronal excitability, and synaptic plasticity, we have carried out experiments with aged mice that lack the auxiliary potassium channel subunit Kvbeta1.1. In aged mice, the deletion of the auxiliary potassium channel subunit Kvbeta1.1 resulted in increased neuronal excitability, as measured by a decrease in the post-burst afterhyperpolarization. In addition, long-term potentiation (LTP) was more readily induced in aged Kvbeta1.1 knockout mice. Finally, the aged Kvbeta1.1 mutants outperformed age-matched controls in the hidden-platform version of the Morris water maze. Interestingly, the enhancements in excitability and learning were both sensitive to genetic background: The enhanced learning was only observed in a genetic background in which the mutants exhibited increased neuronal excitability. CONCLUSIONS: Neuronal excitability is an important determinant of both synaptic plasticity and learning in aged subjects.

Action Potentials↗

Physical stability and moisture sorption of aqueous chitosan-amylose starch films plasticized with polyols.

The short-term stability and the water sorption of films prepared from binary mixtures of chitosan and native amylose maize starch (Hylon VII) were evaluated using free films. The aqueous polymer solutions of the free films contained 2% (w/w) film formers, glycerol, or erythritol as a plasticizer, as well as acetic acid (1%) and purified water. Characterization of the present fresh and conditioned film formers and free films was done using X-ray diffraction analysis, determination of moisture sorption isotherms, and near infrared spectroscopy. The results indicated that clear changes in the crystallinity of the films are evident within a 3-month period of storage, and the changes in the solid state are dependent on the plasticizer and storage conditions. When stored at ambient conditions for 3 months, the aqueous chitosan-amylose starch films plasticized with erythritol exhibited a partly crystalline structure. This was as a result of sugar recrystallisation due to the high hydrogen bonding. The respective films plasticized with glycerol and stored at 25 degrees C/60% relative humidity (RH) or at 40 degrees C/75% RH remained flexible and amorphous for at least 3 months. The water sorption of the free films greatly increased as a function of storage time at 75 and 95% RH. The second derivative spectra of starting material and free films were capable of distinguishing the internal water from the free water after storage at different relative humidities. Free water resulted in a separate band at a lower wavelength (1903 nm) in comparison to the structured absorbed water band at 1920 nm, in the case of films the free water resulted in a band around 1900 nm.

Amylose↗

Use of a temporary plastic stent to facilitate the placement of multiple self-expanding metal stents in malignant biliary hilar strictures.

BACKGROUND: Although endoscopic palliation of malignant biliary hilar obstruction is preferable to surgery or percutaneous drainage, it remains technically challenging. This is especially true when multiple self-expanding metal stents (SEMS) are placed, because difficulty is commonly encountered in passing the second SEMS at the level of the previously deployed initial stent. We have devised a method of deploying multiple metal stents by using a temporary plastic stent, which makes deployment of the second stent much easier. METHODS: After guidewire placement, a plastic stent is deployed in a subhilar position. The initial SEMS is deployed, with the plastic stent maintaining a passage for the second SEMS. After the second SEMS is deployed, the plastic stent is retrieved. OBSERVATIONS: This technique has been used successfully in 7/8 patients, all of whom presented with symptomatic jaundice secondary to malignant hilar obstruction of various etiologies (cholangiocarcinoma, n=4; metastatic disease, n=3; and hepatocellular carcinoma, n=1). Drainage was successful in all cases, with significant improvement in symptoms and cholestasis. CONCLUSIONS: This simple technique lessens the technical difficulty of placing bilateral hilar SEMS.

Adult↗

Effect of plasticization on heparin release from biodegradable matrices.

Heparin-loaded polymer films of poly-L-lactide (PLLA) and poly-L-lactide-co-glycolide (PLLGA) as well as poly-DL-lactide-co-glycolide (PLGA) were produced. A plasticizer, PEG, was added to the polymers. It was found that the release profile in general consisted of a burst effect, a diffusion-controlled phase and a degradation-controlled phase. The plasticizer accelerated the onset of degradation in all cases, but its effect on the release profile differed significantly depending on the polymer. The plasticizer depressed the burst effect for PLLA, and accelerated the kinetics of the diffusion-controlled phase. For the PLLGA 80/20, however, the plasticizer had no significant effect on the release profile or kinetics. We explain these observations in terms of hydrophilicity and crystallinity effects.

Absorbable Implants↗

Effect of plasticizers on properties of pregelatinised starch acetate (Amprac 01) free films.

Film coating is a technique widely used in the pharmaceutical field to improve and modify technological and release characteristics of capsules, tablets and granules. In this paper physical and mechanical properties of free films of Amprac 01, obtained by the solvent cast method, were studied in order to investigate the film forming ability of this modified starch and the effects of the addition of different plasticizers. A morphological microscopical analysis (SEM) was performed to study surface properties of the films, while thermal analysis (DSC) was carried out to investigate the influence of different types of plasticizers on the glass transition temperature of the polymer. Then a mechanical characterization permitted to evaluate important parameters such as film crack resistance and deformation at break. Extensional creep/relaxation tests were also performed to investigate the viscoelastic characteristics. As clearly demonstrated by the T(g) values, the residual water present in the films acted as plasticizers, making possible the formation of free films characterised by good macroscopical and mechanical properties. Except glycerol, the kind and amount of the other tested plasticizers did not markedly improve the mechanical and crack resistance of the films.

Calorimetry, Differential Scanning↗

Plastic laryngeal foreign bodies in children: a diagnostic challenge.

OBJECTIVE: To review Children's Hospital and Regional Medical Center experience with pediatric airway foreign bodies, and examine the incidence and treatment of laryngeal foreign bodies. To determine if plastic laryngeal foreign bodies present differently than other laryngeal foreign bodies. METHODS: A retrospective review of all cases of children (1874 patients) undergoing direct laryngoscopy and/or bronchoscopy from 1st January 1997 to 9th September 2003 at a tertiary care children's hospital. Patients with endoscopically documented laryngeal foreign bodies were identified and the medical record reviewed in more detail. Patient age, gender, foreign body location, foreign body type, duration of foreign body presence, radiographic findings, endoscopic findings and treatment complications were recorded. RESULTS: One hundred and five aspirated foreign bodies were identified. The nine laryngeal foreign bodies included five clear plastic radiolucent items, two radiolucent food items, and two sharp radioopaque pins. Time to diagnosis and treatment was on average 11.6 days with 17.6 days for thin/plastic foreign bodies and 1.6 days for metal/food foreign bodies. CONCLUSION: Laryngeal foreign bodies represent a small portion of all pediatric airway foreign bodies. Difficulty in identifying laryngeal foreign bodies, especially thin, plastic radiolucent foreign bodies can delay treatment. Thin plastic foreign bodies can present without radiographic findings, can be difficult to image during endoscopy and can be particularly difficult to diagnose. A history of choking and vocal changes is associated with laryngeal foreign bodies. Laryngeal foreign bodies should be in the differential diagnosis of all children presenting with atypical upper respiratory complaints especially if a history suggestive of witnessed aspiration and dysphonia can be obtained.

Airway Obstruction↗

Impact of plastic adhesion in vitro on analysis of Th1 and Th2 cytokines and immune cell distribution from mice with multiple low-dose streptozotocin-induced diabetes.

Cytokines produced by Th1 or Th2 cells have been postulated to be important in the development of type 1 diabetes in humans and animal models, such as murine multiple low-dose streptozotocin (MLDSTZ)-induced diabetes. The aim of this study was to investigate cytokine production with or without in vitro depletion of plastic adherent cells from spleens isolated after MLDSTZ treatment. Spleen cells were prepared on day 14 from MLDSTZ- and saline-treated mice and divided into two fractions. One cell fraction was depleted of adherent cells by plastic adherence and the other was not. Both cell fractions were analysed by FACS for the distribution of immune cells. In other experiments, the cells were cultured for 48 h with concanavalin A stimulation. Supernatant samples were analysed by ELISA for TNFalpha, IFNgamma and IL-10 production. Either before or after the 48-h culture cytokine mRNA expression was determined by RT-PCR. Plastic adhesion decreased the macrophage numbers by approximately 30% and CD4(+)CD25(+) cells by about 60%. This was accompanied by increased medium levels of TNFalpha, IFNgamma and IL-10, which suggest that either CD4(+)CD25(+) cells, macrophages, or both, down-regulate production of both Th1 and certain Th2 cytokines. Depletion of adherent cells also decreased IL-4 mRNA amounts. MLDSTZ treatment increased the production of Th1 cytokines mainly at the protein level, and IL-10 mainly at the mRNA level. This indicates a sustained increase in Th1 production after MLDSTZ treatment and an increase in IL-10 that might reflect an attempt to counteract the MLDSTZ-induced immune damage. Plastic adhesion during cell preparation may affect the relative distribution of certain immune cells.

Animals↗

Brain plasticity: from pathophysiological mechanisms to therapeutic applications.

Cerebral plasticity, which is the dynamic potential of the brain to reorganize itself during ontogeny, learning, or following damage, has been widely studied in the last decade, in vitro, in animals, and also in humans since the development of functional neuroimaging. In the first part of this review, the main hypotheses about the pathophysiological mechanisms underlying plasticity are presented. At a microscopic level, modulations of synaptic efficacy, unmasking of latent connections, phenotypic modifications and neurogenesis have been identified. At a macroscopic level, diaschisis, functional redundancies, sensory substitution and morphological changes have been described. In the second part, the behavioral consequences of such cerebral phenomena in physiology, namely the "natural" plasticity, are analyzed in humans. The review concludes on the therapeutic implications provided by a better understanding of these mechanisms of brain reshaping. Indeed, this plastic potential might be 'guided' in neurological diseases, using rehabilitation, pharmacological drugs, transcranial magnetic stimulation, neurosurgical methods, and even new techniques of brain-computer interface - in order to improve the quality of life of patients with damaged nervous systems.

Animals↗

Endogenous plastic composite material in the Alzheimer's brain.

Accumulation of amyloid beta (Abeta) peptide in brain is the hallmark of Alzheimer's disease (AD). The resulting plaques though fibrous in nature may also consist of additional structures currently poorly defined. We hypothesize that plastic composite material contributes to plaque formation. This material is organized by polymers of acrolein, which is an oxidized lipid fragment found in AD. Acrolein, a 3-carbon compound, contains a carbonyl and a vinyl group that participate in polymerization via fundamental latex chemistry. The redox and surfactant properties of Abeta allow it to catalyze the polymerization of acrolein. We previously reported observations of thin plastic fragments of Abeta-polyacrolein. The current paper outlines the proposed steps in forming these plastic fragments. Endogenous plastic composite material may significantly contribute to the pathogenesis of AD.

Acrolein↗

Overexpression of the full-length neurotrophin receptor trkB regulates the expression of plasticity-related genes in mouse brain.

Significant body of evidence indicates an important role for brain-derived neurotrophic factor (BDNF) in the hippocampal synaptic plasticity; however, the exact mechanisms how the BDNF signal is converted to plastic changes during memory processes are under an intense investigation. To specifically address the role of the trkB receptor, we have previously generated transgenic mice overexpressing the full-length trkB receptor and observed a continuous activation of the trkB.TK+ receptor, improved learning and memory but an attenuated LTP in these mice. In this study, we describe the trkB.TK+ mRNA and protein distribution in the transgenic mice, showing the most prominent increase in the full-length trkB expression in the cortical layer V pyramidal neurons and dentate gyrus of the hippocampus. In addition, we have analyzed the mRNA expression patterns of a group of genes associated with both plastic changes in the nervous system and BDNF signaling. Regulated expression of immediate early genes c-fos, fra-2 and junB was observed in the transgenic mice. Furthermore, the mRNA expression of alpha-Ca2+/calmodulin-dependent kinase II (alpha-CaMKII) was reduced in both the hippocampus and parietal cortex, whereas growth-associated protein 43 (GAP-43) mRNA expressions were induced in the corresponding regions. Conversely, the mRNA expression of the transcription factor cAMP response element binding protein (CREB) was not altered in the trkB.TK+mice. Finally, the density of neuropeptide Y (NPY)-expressing cells was increased in the trkB.TK+ mice dentate hilus. Altogether, these results demonstrate in vivo that the increased trkB.TK+ signaling regulates several important plasticity-related genes.

Animals↗

Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD. We examined the impact of the HD transgene upon learning-dependent plasticity of cortical representational maps. The effect of associative learning, in which stimulation of a row of vibrissae was paired with appetitive stimulus, upon functional representations of vibrissae in the barrel cortex, was investigated with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type mice, cortical representation of the row of vibrissae involved in the training was expanded, while in HD mice the representation of this row was not expanded. The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in plasticity of primary somatosensory cortex.

Animals↗