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Biomedical subjects

B Kolb

Publications and source records attributed to B Kolb.

At least 55 records · Page 3Linked to original sources

Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis.

In order to characterize the autoimmune response participating in the pathogenesis of rheumatoid arthritis (RA) a cDNA expression library constructed from mRNAs which had been isolated from the inflamed synovium of an RA patients was screened with autologous IgG autoantibodies. This led to the identification of gene rasi-1 which encodes a protein showing sequence identity with the zinc-binding matrix metalloproteinase MMP-19. MMP-19 is detected on the surface of activated PBMCs, TH1 lymphocytes, and Jurkat T lymphoma cells. It exhibits gelatinolytic activity and is recognized by autoantibodies in 26% and, respectively, 33% of sera collected from RA patients and systemic lupus erythematosus (SLE) patients. The novel autoantigen MMP-19 thus could play a role in the pathological processes participating in RA-associated joint tissue destruction.

Amino Acid Sequence↗

Sex differences in the effects of frontal cortex injury: role of differential hormonal experience in early development.

The extent to which sex differences in the behavioral effects of frontal injury in the adult rat can be attributed to differential exposure to testosterone (T) during development was investigated. The effects of these factors on brain weight and relative brain size were also examined. At birth, males were gonadectomized (GDX) or not and females were given T or oil injections. In adulthood, all animals were GDX or sham-operated and received either bilateral aspiration lesions of the medial frontal cortex or a sham operation. Rats were tested on the Morris water maze task, the radial arm maze (RAM), and the landmark water task. The effects of frontal injury on performance of the Morris water maze task were greater in rats not exposed to T at birth, there was no effect of neonatal T exposure on performance on the RAM, and on the landmark water task there was a complicated interaction of sex and neonatal T exposure in rats with frontal injury.

Animals↗

Brain plasticity and behavior.

Brain plasticity refers to the brain's ability to change structure and function. Experience is a major stimulant of brain plasticity in animal species as diverse as insects and humans. It is now clear that experience produces multiple, dissociable changes in the brain including increases in dendritic length, increases (or decreases) in spine density, synapse formation, increased glial activity, and altered metabolic activity. These anatomical changes are correlated with behavioral differences between subjects with and without the changes. Experience-dependent changes in neurons are affected by various factors including aging, gonadal hormones, trophic factors, stress, and brain pathology. We discuss the important role that changes in dendritic arborization play in brain plasticity and behavior, and we consider these changes in the context of changing intrinsic circuitry of the cortex in processes such as learning.

Animals↗

Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine.

Experience-dependent changes in behavior are thought to involve structural modifications in the nervous system, especially alterations in patterns of synaptic connectivity. Repeated experience with drugs of abuse can result in very long-lasting changes in behavior, including a persistent hypersensitivity (sensitization) to their psychomotor activating and rewarding effects. It was hypothesized, therefore, that repeated treatment with the psychomotor stimulant drug amphetamine, which produces robust sensitization, would produce structural adaptations in brain regions that mediate its psychomotor activating and rewarding effects. Consistent with this hypothesis, it was found that amphetamine treatment altered the morphology of neurons in the nucleus accumbens and prefrontal cortex. Exposure to amphetamine produced a long-lasting (>1 month) increase in the length of dendrites, in the density of dendritic spines, and in the number of branched spines on the major output cells of the nucleus accumbens, the medium spiny neurons, as indicated by analysis of Golgi-stained material. Amphetamine treatment produced similar effects on the apical (but not basilar) dendrites of layer III pyramidal neurons in the prefrontal cortex. The ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to some of the long-term behavioral consequences of repeated amphetamine use, including amphetamine psychosis and addiction.

Amphetamine-Related Disorders↗

Nerve growth factor stimulates growth of cortical pyramidal neurons in young adult rats.

The cytoarchitectonics of pyramidal neurons in the cerebral cortex of non-lesioned rats can be re-modeled by i.c.v. infusions of nerve growth factor (NGF). 4 months after the application of NGF, the pyramidal neurons in layers III and V of the motor cortex and layer V of the anterior cingulate cortex were analyzed and compared with pyramidal neurons from vehicle-treated rats. NGF-treated brains showed: (1) significant increase in dendritic branching in the basilar fields of the layer V, but not layer III, neurons; and (2) a significant increase in spine density in the terminal, but not proximal, dendritic branches. These findings indicated that, besides its known effects on forebrain cholinergic neurons, NGF produces a very generalized synaptic re-modeling involving the cells responsible for the major output of the cerebral cortex in the intact adult brain.

Animals↗

Recovery of function is associated with increased spine density in cortical pyramidal cells after frontal lesions and/or noradrenaline depletion in neonatal rats.

Rats were given medial frontal lesions at 7 days of age and were tested as adults on tests of forelimb use, forelimb tactile sensitivity, tongue use, hindleg use, and in a spatial navigation task. The brains were processed with a modified Golgi-Cox procedure and dendritic arborization and spine density was measured. The animals showed recovery only on the spatial task and this was associated with an increase in the number of spines per unit length of dendrite. We also reanalyzed Golgi-Cox stained material from an experiment in which animals were depleted of cortical noradrenaline (NA) in infancy and then given frontal lesions on day 7. The NA depletion blocked the recovery from frontal lesions. Analysis of dendritic morphology showed that in otherwise intact rats, NA depletion decreased dendritic arbor but increased spine density to the level of frontal operates. Depleted frontal-operates showed no additional increase in spine density and also showed a decrease in dendritic arborization. These results suggest that recovery from neonatal cortical injury and from neonatal noradrenaline depletion may be supported by changes in both the dendritic arborization and the spine density in the remaining cortex.

Animals↗

Nerve growth factor treatment prevents dendritic atrophy and promotes recovery of function after cortical injury.

This study examined the behavioural and anatomical effects of intraventricular injections of nerve growth factor in rats with unilateral damage that included Zilles' areas Frl, FL, HL, ParI and the anterior portion of Oc2. Nerve growth factor-treated lesion rats showed attenuation of behavioural symptoms in measures of forelimb function (Whishaw reaching task) and hindlimb function (beam traversing task) as well as a measure of spatial navigation (Morris water task). Analysis of dendritic arborization using a modified Golgi. Cox procedure also showed a complete reversal of lesion-induced atrophy of dendritic fields in pyramidal neurons in motor (Zilles' Fr2) and cingulate (Zilles' Cgl) cortex. In addition, there was a reversal of a lesion-induced reduction in spine density. These results demonstrate that nerve growth factor treatment can facilitate functional recovery from cortical injury. This recovery may be mediated by a reorganization of intrinsic cortical circuitry that is reflected in changes in dendritic arborization and spine density of pyramidal neurons.

Animals↗

Blockade of basic fibroblast growth factor retards recovery from motor cortex injury in rats.

The endogenous expression of basic fibroblast growth factor (bFGF) was blocked by neutralizing antibodies following unilateral suction lesions of the motor cortex. Rats with control treatment (saline, goat IgG) after motor cortex lesions showed slow recovery of forelimb manipulatory abilities. Rats with blockade of bFGF expression showed little recovery. Anatomically, the control-treated lesioned rats showed an acute increase in bFGF and glial fibrillary acidic protein (GFAP) reactivity, and chronically they had normal dendritic arborization and spine density in layer V pyramidal cells in the remaining motor cortex. In contrast, rats treated with antibodies to bFGF showed little bFGF reactivity, normal GFAP reactivity, and atrophy of dendritic arbor and decreased spine density in layer V pyramidal cells. These results demonstrate the importance of endogenous bFGF release in processes related to functional recovery after cortical injury.

Animals↗

Unilateral lesions of the forelimb area of rat motor cortex: lack of evidence for use-dependent neural growth in the undamaged hemisphere.

Unilateral lesions of the forelimb area of the motor cortex have been reported to produce enhanced dendritic outgrowth in the undamaged hemisphere in response to the behavioral asymmetry produced by the lesions (e.g. Jones, T.A. and Schallert, T., Use-dependent growth of pyramidal neurons after neocortical damage, J. Neurosci, 14 (1994) 2140-2152). We attempted to replicate this result and to determine if there were sex differences in cortical plasticity using the Jones and Schallert model. Animals were given either unilateral aspiration or electrolytic lesions of the forelimb area of the motor cortex or a sham operation. Use of the forelimb ipsilateral to the lesion for postural support was assessed pre- and postsurgery. Eighteen days after surgery the animals were sacrificed. and the brains processed for Golgi-Cox staining or a series of other stains for acetylcholine, astrocytes (glial fibrillary acidic protein), and microglia (OX-42). Although the lesions produced significant behavioral asymmetry and enhanced glial response on the lesioned side, there was little evidence for use-dependent neural growth in the undamaged hemisphere in either sex.

Acetylcholine↗

Does dendritic growth underly recovery from neonatal occipital lesions in rats.

Rats were given lesions of visual cortex on postnatal day 4 or 10, or in adulthood. Ninety days later they were trained on a horizontal-vertical stripes discrimination task and a visual-spatial navigation task. None of the operated rats acquired the tasks. The brains were processed for Golgi-Cox staining and dendritic arborization was quantified in the layer III pyramidal cells in somatosensory cortex. Relative to normal control brains, the neurons of the day 4 and adult operates showed a reduction in dendritic branching, whereas the neurons of the day 10 operates had a significant increase in dendritic arborization. This arborization may be related to enhanced somatosensory function but does not support recovery of visually-guided behavior.

Animals↗

Recovery from early cortical damage in rats, VII. Comparison of the behavioural and anatomical effects of medial prefrontal lesions at different ages of neural maturation.

Rats with removal of the medial prefrontal (mPFC) cortex at days 3, 6, 9, 15, or 30 were compared behaviourally and anatomically to littermate controls. In contrast to adult operates, mPFC lesions at all young ages led to the development of an abnormally thin cortical mantle. In addition, although there was an obvious cavity in brains examined in the early postoperative period, the brains of animals with lesions at day 9 or 15 had no lesion cavity in adulthood as part of the cortex appeared to regrow. The differential anatomical consequences of the lesions at days 9 and 15 was correlated with a differential behavioural outcome as well. Thus although rats in all young lesion groups showed a milder behavioural syndrome than rats with comparable lesions in adulthood, the functional outcome was best for animals with lesions at 9 days of age.

Aging↗

Sex-related differences in cortical function after medial frontal lesions in rats.

The effects of sex on the performance of 4 spatial mazes (Morris water task, landmark task, radial arm maze, and egocentric radial arm maze) were studied in male and female rats given medial frontal lesions. Operated rats from both sexes were impaired at all of the tasks, but the frontal males were much less impaired than frontal females on the Morris task and the radial arm maze, both of which require animals to use multiple visual-spatial cues for their successful solution. Males also performed better on the egocentric maze. In contrast, frontal females performed better than frontal males at the landmark task, which is best solved by using a single spatial cue. The only sex difference in unoperated rats was a small advantage for females on the egocentric task. The sex differences may reflect an underlying difference in cortical organization or a differential response to cortical lesion in males and females.

Animals↗

Changes in the neonatal gonadal hormonal environment prevent behavioral sparing and alter cortical morphogenesis after early frontal cortex lesions in male and female rats.

The effects of perinatal exposure to testicular hormones were studied in male and female rats given medial prefrontal lesions (PFC) on Postnatal Day 7. Hormonally intact rats with PFC lesions showed recovery of performance of the Morris water task but no recovery on a forelimb reaching task. Recovery was abolished in both males gonadectomized at birth and in females given testosterone at birth. Male rats with PFC lesions showed an increase in pyramidal cell spine density. This was blocked in gonadectomized animals. In contrast, female rats with PFC lesions showed an increase in dendritic arbor. This was reduced by perinatal testosterone. Interference with the gonadal hormonal environment reduced the brain's ability to compensate for the effects of early cortical lesions.

Animals↗

Dendritic branching in cortical pyramidal cells in response to ovariectomy in adult female rats: suppression by neonatal exposure to testosterone.

Female Long-Evans rats were treated with oil or testosterone propionate (TP) at birth (postnatal day zero, PN0) and PN1. As adults, animals from each group were ovariectomized or sham operated. Four months later the brains were prepared using a modified Golgi-Cox staining procedure. In neonatally oil-treated females, ovariectomy in adulthood increased the dendritic arbor of layer II/III pyramidal neurons of the parietal cortex; in addition, there were modest increases in apical dendritic spine density. The dendritic arbor of the pyramidal neurons of intact neonatally TP-treated females was greater than that of intact oil-treated females, but in these animals there was no increase in dendritic arbor in response to ovariectomy.

Animals↗

Neonatal frontal cortex grafts fail to attenuate behavioural deficits or abnormal cortical morphogenesis.

Following bilateral removal of the medial frontal cortex, which included the medial prefrontal and adjacent midline motor cortex, 4-day-old rats were given transplants of embryonic day 17 frontal cortical tissue. Other rats were given only frontal lesions or sham operations. In adulthood, the animals were trained on a spatial navigation task and a forelimb reaching task. The transplanted tissue grew well and interacted morphologically with the host but the grafts failed to reduce the spatial navigation and motor deficits resulting from the frontal removals. The grafts also failed to reduce the anatomical sequelae of the early lesions, which included cortical thinning and thalamic shrinkage. It appears unlikely that cortical transplantation will be a viable treatment for recovery from perinatal frontal cortical injury.

Animals↗

Neonatal frontal cortical lesions in rats alter cortical structure and connectivity.

Rats were given frontal cortical lesions at day 1 or 10 of life. Later, as adults, they were either: (1) processed with Golgi-Cox in order to analyze cortical dendritic arborization; (2) given injections of True Blue into the parietal or visual cortex, or (3) given injections of [3H]leucine into the substantia nigra. An additional group of normal rats were given injections of fluorescent dyes into the cortex on day 4 or 10 of life. The main findings were that (1) adult hemispheres with day 10 lesions had greater dendritic arbor than normal hemispheres, (2) adult hemispheres with day 1 lesions had reduced dendritic branching relative to normal hemispheres, (3) adult rats with day 10 lesions had no obvious abnormalities in cortical connections, (4) adult rats with day 1 lesions had abnormal thalamo-cortical, amygdalo-cortical, and nigro-cortical connections, and (5) many of these abnormal connections were present in the brains of 4-day-old normal rats. Since the 'abnormal' connections in the very early frontal operates were present in day 4 animals, it appears that they result from the failure of exuberant connections to retract after the lesions. The increased dendritic growth in day 10 operates does not appear related to qualitative changes in cortical afferents or efferents and may related to increased intrinsic cortical connectivity. Since rats with day 10 lesions have previously been shown to exhibit significant recovery of function, it is possible that the increased dendritic arborization is supporting the functional restitution.

Aging↗

Acquisition of conditional discriminations in hippocampal lesioned and decorticated rats: evidence for learning that is separate from both simple classical conditioning and configural learning.

This study examined whether hippocampal or neocortical lesions would impair acquisition of a discrimination task using taste aversions. Rats were injected with a drug 15 min before a flavored solution-lithium chloride pairing. On alternate days, vehicle injections preceded and followed access to the same flavored solution. Rats learned to consume significantly more of the flavored solution after vehicle injections than after drug injections. Rats with hippocampal lesions or neonatal decortication performed as well as controls. Rats with hippocampal lesions also learned a similar task in which visual and textural cues predicted whether access to a flavored solution would be followed by an injection of lithium chloride or vehicle. However, these hippocampal lesions did impair performance in the Morris water task. Occasion setting may involve a type of learning dissociated from both simple classical conditioning and configural learning.

Animals↗

Comparison of European and American techniques for the analysis of volatile organic compounds in environmental matrices.

The United States Environmental Protection Agency has promulgated methods for analysis of volatile organic compounds by purge and trap, or dynamic headspace, gas chromatography. In western Europe, where environmental analyses are less heavily regulated, static headspace is widely used. In this paper, these two approaches are compared and contrasted for use with different environmental matrices. The theoretical basis and state of application for purge and trap and headspace analysis are discussed, and data are presented on the accuracy and precision of both approaches. Data are reported on the use of headspace analysis for different aqueous matrix types with different sample preparation procedures. A new method for direct headspace analysis of soil samples is presented and compared with the EPA-approved purge and trap method.

Chromatography, Gas↗