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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 307 records · Page 17Linked to original sources
PubMed1987

The innervation of intraocular spinal cord transplants by cografts of locus ceruleus and substantia nigra neurons.

The nucleus locus ceruleus and the substantia nigra were sequentially cografted with spinal cord in the anterior chamber of the eye of adult rats. The double grafts were allowed to mature in oculo. After a survival time of 2 months, half of the number of rats were sacrificed, the grafts were dissected out and prepared for tyrosine hydroxylase immunohistochemistry and Falck-Hillarp monoamine histochemistry. The remaining animals were sacrificed after 12-14 months and processed according to the same protocol. No ingrowth from the sympathetic ground plexus in the host iris was seen in single spinal cord grafts at any of the survival times. At the shorter survival time there were no or very few catecholaminergic nerve fibers from the locus ceruleus or substantia nigra that were innervating the spinal cord cograft. In double grafts that were allowed to remain in oculo for 12-14 months, the entire spinal cord graft was innervated with varicose, catecholamine-containing nerve fibers. The locus grafts were able to innervate the spinal cord cografts much more densely than the substantia nigra grafts. In conclusion, the results demonstrate that isolated intraocular spinal cord grafts can be innervated by adjacent central catecholamine neurons. However, this is done in a delayed manner as compared to other models. The isolated replicas of descending adrenergic pathways to the spinal cord thus formed should provide useful information about the function of descending spinal catecholamine pathways.

Animals↗
PubMed1987

Age-related changes in cerebellar noradrenergic pre- and postsynaptic mechanisms: intrinsic vs extrinsic determinants evaluated with brain grafts in oculo.

Intrinsic versus extrinsic determinants of changes in cerebellar noradrenergic transmission during senescence in the rat were measured using homologous cerebellar grafts in oculo. Postsynaptic sensitivity of Purkinje neurons to catecholamines was determined by perfusing the anterior eye chamber with known concentrations of norepinephrine (NE) dissolved in a balanced salt solution. NE elicited a dose-dependent slowing of spontaneous Purkinje neuron discharge in both young (3-6 months) and aged (20-22 months) cerebellar grafts. Hill plots demonstrated that the dose-response relationships in both age-groups were linear and parallel to one another. Aged transplant Purkinje neurons manifested a marked and highly significant subsensitivity to NE with an EC50 of 583 microM, as compared with an EC50 of only 15.9 microM in the young grafts. Young grafts in 15-21-month-old hosts manifested an EC50 of 20 microM for the depressant actions of NE. Collaterals of host iris sympathetic fibers innervate the grafts. Activity of these fibers can be reflexly altered by changing illumination of the retina. The dynamics of presynaptic NE release from these fibers was evaluated using in vivo electrochemistry with Nafion-coated graphite epoxy capillary electrodes, which are highly selective for the monoamine neurotransmitters. As illumination of the ipsilateral retina is increased, the release of catecholamine in the cerebellar graft decreases. A mean change in the extracellular electroactive species of 4.2 +/- 0.6 microM was found in young cerebellar grafts. Equivalent stimuli induced a mean change of 2.3 +/- 0.8 microM in aged grafts. However, this diminished release was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Studies on the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice. Comparison with three other strains of mice.

The effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice has been studied employing neuro- and histochemical techniques. The number of dopamine (DA) cell bodies in substantia nigra pars compacta (SNC) was reduced by 70% in MPTP-treated C57BL/6 mice, as demonstrated both by tyrosine hydroxylase (TH) immunohistochemistry and conventional histology (Cresyl violet staining) and an almost complete loss of DA fibers in striatum was also found. A detailed analysis of the effects of MPTP on endogenous catecholamine levels in various brain regions revealed that MPTP caused a severe reduction of endogenous DA in substantia nigra and striatum (35 and 5% of control) which was accompanied by an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. There was also a decrease of DA in nucleus accumbens and the olfactory tubercle to 41 and 44% of control, respectively, without any significant change in the DOPAC/DA ratio and density of TH-positive fibers. Small but significant decreases of the noradrenaline (NA) levels in septum, entorhinal cortex and frontal cortex were seen, although the uptake of [3H]NA in frontal cortex was not significantly changed. Minor MPTP-induced decreases of the serotonin levels in frontal cortex, occipital cortex and spinal cord were also seen. The MPTP treatment also induced a 55% increase of adrenaline levels in hypothalamus, while no changes were seen in pons-medulla and spinal cord. Comparing this with 3 other strains of mice, the MPTP-induced reduction of endogenous DA in striatum was most pronounced in C57BL/6, less in N.M.R.I. and CBA/Ca mice, and least in Swiss-Webster. Concerning the effect of MPTP on cortical NA levels, the same relation was at hand except for C57BL/6, where, as mentioned, the effect was merely detectable. No reduction of DA perikarya in SNC was seen in Swiss-Webster mice. These findings show that in mice major differences exist in sensitivity of catecholamine neurons to MPTP between different strains. The data show that MPTP can produce an almost complete, permanent and relatively selective degeneration of the nigrostriatal DA neurons in C57BL/6 mice similar to that seen in primates. This strain may therefore serve as a useful model for studies on various aspects of MPTP-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen.

Autologous adrenal medullary tissue was transplanted unilaterally to the putamen in two patients with severe Parkinson's disease. The first patient exhibited a transient, two-day improvement of motor performance in the limbs contralateral to the implantation site. He also had significantly longer episodes of normal function for about two months. The second patient reported a minor improvement of balance and gait, again lasting for two months. Electrophysiological studies of the motor readiness and auditory evoked potentials were consistent with increased catecholaminergic activity in the basal ganglia after transplantation in both patients. Positron emission tomography showed no postoperative alteration of receptor density in the putamen. No significant adverse effects of the transplantation were observed in the patients' performance on neurological and psychological tests or in their quantitative electroencephalogram and cerebral blood flow recordings. Immediately after the grafting, one patient showed transient signs of sympathetic hyperactivity, probably caused by release of catecholamines from the implanted tissue into the peripheral circulation. We conclude that catecholamine-rich cellular implants in the basal ganglia have transient beneficial effects in patients with severe Parkinson's disease.

Adrenal Medulla↗
PubMed1987

Nerve growth factor protein level increases in the adult rat hippocampus after a specific cholinergic lesion.

Nerve growth factor (NGF) is the best-characterized neurotrophic substance and has recently been shown to influence cholinergic neurons in the basal forebrain. Hippocampus and neocortex, the primary targets for these central neurons, have further been found to contain high levels of NGF. Using enzyme immunoassay and acetylcholine esterase (AChE) histochemistry we have now studied the levels of NGF and AChE after a specific cholinergic lesion, transection of the fimbria fornix comprising the major cholinergic input to hippocampus. Fimbriectomy in adult rats led to a marked decrease in AChE-positive nerve terminals in both hippocampus and neocortex 10 days later, and to an increase (40%) of NGF protein concentration in hippocampus. thirty days after surgery, NGF had returned to control levels and remained there after 90 days. Removal of superior cervical ganglion did not alter the results. The density of cholinergic terminals in both hippocampus and neocortex increased with time (90 days) after fimbrial transection. The results support the idea that cholinergic neurons in the basal forebrain take up and retrogradely transport NGF from their target areas and suggest that transection of the pathway interrupts the transport thereby increasing NGF distal to the lesion. The return of NGF to control levels probably reflects reestablished cholinergic contracts in the hippocampus.

Animals↗
PubMed1987

Glutamic acid decarboxylase- and peptide-immunoreactive neurons in cortex cerebri following development in isolation: evidence of homotypic and disturbed patterns in intraocular grafts.

Fetal parietal cerebral cortex was transplanted to the anterior eye chamber of adult Sprague-Dawley rats. After two to three months the grafts, with or without colchicine treatment, were subjected to immunohistochemical analysis using antibodies against cholecystokinin (CCK), somatostatin (SOM), neuropeptide tyrosine (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Cerebral cortex in situ of untreated and colchicine-treated rats was always analyzed in parallel. A dense plexus of CCK-immunoreactive fibers was distributed in all parts of the transplants, and after colchicine treatment a large number of CCK-positive cells was observed. These cells were markedly increased in number as compared to normal cortical tissue in colchicine-pretreated rats. The amount of NPY-immunoreactive cells was also markedly increased, whereas somatostatin-positive cells were found in numbers similar to those seen in cortex in situ. In the grafts only a few VIP- and PHI-positive fibers were seen with a few VIP-positive cell bodies, but no clearly discernible PHI-positive cells. A very dense plexus of GAD-positive fibers with an even distribution throughout the grafts was observed. Cortex in situ exhibited a lower density of GAD-immunoreactive fibers. Even after colchicine treatment the number of GAD-positive cells in the grafts was low. Using double-staining techniques, it was found that most of the few GAD-positive cells in the grafts were also NPY-positive, SOM-positive or, to a minor extent, CCK-positive. The present results demonstrate that several peptides and transmitter markers are expressed in cortical grafts in oculo, but marked differences in their expression can be observed in cortical tissue that has developed in isolation. Thus, the intraocular cortex graft, alone and in combination with other brain areas, should provide a useful model in which to study factors that regulate brain development.

Animals↗
PubMed1987

Nerve growth factor-like immunoreactivities in rodent salivary glands and testis.

A series of polyclonal affinity-purified antibodies against mouse submandibular-gland nerve growth factor (NGF) are described. Using the submandibular gland of the male mouse and indirect immunofluorescence, the specificity and sensitivity of affinity-purified immunoglobulins and various other fractions from the immunized animals have been tested. It will be shown that affinity-purification schemes, including pre-purification of protein A-fractionated immunoglobulins to remove antibodies that bind to unrelated hydrophilic and hydrophobic proteins, significantly enhance the signal-to-noise ratio and specificity of the antibodies. The antibodies effectively detect NGF-like immunoreactivity in both fresh and fixed glandular tissue. Optimal fixation procedures are described. Fluorescence intensities are linearly correlated to log antibody concentration. By use of the best antibody fractions and optimal fixation protocols, the distribution of NGF-like immunoreactivity is described in eight different salivary glands (rat and mouse, male and female, submandibular and sublingual glands). In addition to the well-known large numbers of immunoreactive cells in the submandibular gland of the male mouse, immunoreactive cells were found in the sublingual gland of male mice and in the submandibular and sublingual glands of female mice. One antibody revealed a weak specific fluorescence also in the submandibular gland of the male mouse. In a survey of genital organs of male mice, one antibody revealed fluorescence in the germ cell line. We conclude that several polyclonal affinity-purified antibodies have been characterized that show a strong NGF-dependent binding to the secretory granules of tubular cells in the submandibular gland of male mice. These antibodies should make it possible to locate endogenous and perturbed NGF levels immunocytochemically, e.g., in the peripheral and central nervous system, where NGF concentrations may be several orders of magnitude lower than in the salivary glands.

Animals↗
PubMed1987

Galanin-immunoreactive nerves in the rat iris: alterations induced by denervations.

The iris and choroid membrane of the adult rat contain nerve fibers expressing immunoreactivity to the neuropeptide galanin. The density and distribution of galanin-positive nerve fibers varied from iris to iris and, particularly, among animals. Smooth, non-terminal axons were seen running in nerve bundles consisting of otherwise negative fibers. From the choroid membrane these bundles reached the iris via the ciliary body. Axons were frequently seen to branch giving rise to a sparse system of varicose, single fibers in the dilator plate and sphincter area. Galanin-positive fibers were sometimes also seen outlining blood vessels. Capsaicin, in a dose that causes permanent depletion of substance P- and cholecystokinin-immunoreactive fibers in the iris, caused no change in amount of galanin-positive fibers. Removal of the superior cervical ganglion caused a rapid and pronounced increase in the number of galanin-immunoreactive nerve fibers. Similarly, removal of the ciliary ganglion appeared to increase galanin immunoreactivity, while removal of the pterygopalatine ganglion was less effective. Lesioning of the trigeminal ganglion caused a disappearance of galanin immunoreactivity. The sympathectomy-induced increase was counteracted by capsaicin. Galanin-positive nerve cell bodies were present in both the superior cervical and the trigeminal ganglia. In the superior cervical ganglion, immunoreactive galanin did not seem to coexist with neuropeptide Y-positive cells; in the trigeminal ganglion, some galanin-positive cells also contained calcitonin gene-related peptide (CGRP) immunoreactivity, while most cells did not. In the iris, double-staining suggested that CGRP and galanin immunoreactivities were contained in different fiber populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Sustained seizures cause circumscribed cerebral changes in glial fibrillary acidic protein, neurofilament and laminin immunofluorescence.

Sustained experimental seizures in rats have previously been shown to cause an extensive necrosis in pars reticulata of substantia nigra (SNPR) and globus pallidus (GP). In the present paper we have studied the effects of hexafluorodiethyl ether-induced seizures on the immunoreactivity seen with antibodies directed against glial fibrillary acidic protein, GFA, used to visualize astrocytes, antibodies to the glycoprotein laminin as a marker for blood vessel walls and neurofilament (NF) antibodies to monitor neuronal disturbances. Already 12 h after a 20-min seizure period a reduction in GFA immunofluorescence intensity was observed in SNPR. After 3 days, marked lesions were noted in SNPR and GP as seen with cresyl violet staining. The lesions contained almost no GFA-positive structures. In the proximity of the lesions, an increase in GFA-immunoreactivity was noted. Such an increase, although less pronounced, was also seen in the major projection areas of SNPR. Two months post-seizure, the gliotic reaction had disappeared, and only a thin and elongated gliotic scar was observed. In spite of the development of a profound central necrosis especially evident in SNPR, both laminin- and NF-immunoreactivity was slightly increased within the lesioned areas. NF-immunoreactivity was also increased in the superior colliculus and in the reticular formation. Two months post-experiment NF-immunofluorescence was normalized but the former lesion sites showed signs of hypervascularization. We conclude that hexafluorodiethyl ether-induced 20-min seizures lead to rapid, localized glial and neuronal changes in the rat brain as evidenced by GFA and NF immunohistochemistry, while the vascular network remains intact.

Animals↗
PubMed1987

Human fetal tissues grafted to rodent hosts: structural and functional observations of brain, adrenal and heart tissues in oculo.

The potential for growth and development of human tissue grafts was explored by transplantation to the anterior chamber of the eye of rats and mice. Tissues were obtained from therapeutic abortions, performed in the eighth to twelfth week of gestation, using a slight modification of routine vacuum aspirations. Recipients were either adult rats immunosuppressed with cyclosporin A and protected with antibiotics, or nude immunodeficient Balb C mice. Catecholamine-rich tissues such as chromaffin cells from the adrenal medulla, sympathetic ganglia, central dopamine neuroblasts from the substantia nigra, and noradrenaline neuroblasts from the locus coeruleus all survived grafting, and in many cases formed nerve fibers that invaded the host iris. Similarly, central serotonin neurons from developing raphe nuclei grafts were able to innervate host irides. Human fetal cerebellar and cerebral cortical transplants continued their development in rat host eyes. Extracellular recordings from such cerebellar and cortical grafts revealed spontaneously active cells with immature action potential waveforms. Spinal cord grafts also survived and contained substance P-immunoreactive neurons. Dorsal root ganglia were able to form nerve fibers invading the host iris, as evidenced by neurofilament immunohistochemistry. Heart tissue survived and manifested spontaneous rhythmic contractions in oculo. Both human cortex cerebri and heart tissue grafts became innervated by sympathetic adrenergic nerve fibers from the rat host iris. Thus both graft-to-host and host-to-graft neuronal connections may be established between man and rat. Taken together, these data suggest that transplantation of human fetal nervous tissues to the anterior chamber of immunosuppressed or immunodeficient rodent hosts yields a unique model system for studies of human brain development, developmental disturbances, connectivity, and the action of drugs.

Action Potentials↗
PubMed1987

Decreased level of nerve growth factor (NGF) and its messenger RNA in the aged rat brain.

Trophic factors such as nerve growth factor (NGF) are thought to support survival, differentiation and maintenance of neurons. Recent results indicate that NGF produced in cortical and hippocampal areas is required for the function of cholinergic neurons in the basal forebrain. With the use of enzyme immunoassay and RNA blot hybridization we studied the NGF protein and NGF mRNA, respectively, in regions of the brain innervated by basal forebrain cholinergic neurons in adult and aged rats. Levels of NGF protein were decreased by 40% in hippocampus of aged (28 months) Fischer 344 rats compared with adults (6 months), whereas no alterations were observed in cerebral cortex. Moreover, a reduction by 50% in the NGF mRNA was found in samples of the aged forebrain (cerebral cortex, hippocampus, basal forebrain and hypothalamus) compared to the adult. NGF deficiencies may thus account for the loss of cholinergic neurons in the basal forebrain generally found to accompany normal aging and resulting in altered cognitive functions.

Aging↗
PubMed1987

Human fetal cerebellar and cortical tissue transplanted to the anterior eye chamber of athymic rats: electrophysiological and structural studies.

Human fetal tissue fragments from cortex cerebri and cerebellum were grafted to the anterior chamber of the eye of adult athymic nude rats. The grafts were obtained from tissue fragments recovered after elective routine abortions, performed in weeks 8-11 of gestation. Both cerebellar and cortex cerebri grafts survived and developed in the anterior chamber of the eye for 1-4 months. The transplants slowly became vascularized from the host iris. The grafts developed blood vessels with laminin-immunoreactive walls and contained relatively high amounts of glial fibrillary acidic protein- and neurofilament-immunoreactivity in the neuropil after 4 months in oculo. Recordings of extracellular action potentials from the grafts revealed spontaneously active neurons with action-potential waveforms similar to those observed in immature rodents. Morphologically, the grafts showed no signs of rejection. Clusters and bands of large neurons resembling Purkinje cells and dense aggregates of smaller granule-like cells could be found in the cerebellar grafts. Large neurons were also seen in the cortex grafts. Taken together, these data suggest that the athymic rat may serve as a useful tool for studies of central nervous system tissue from otherwise immunologically incompatible species.

Action Potentials↗
PubMed1987

Toxic effects of lead in the developing nervous system: in oculo experimental models.

Modern man is chronically exposed to lead in the biosphere at levels several orders of magnitude higher than the natural level that once existed. There is much concern about the possible adverse effects of this population-wide, low-level lead exposure, particularly on the developing organism, wherein the central nervous system may be one primary target. We have developed in oculo test systems, which permit temporal and spatial discrimination of possible effects of lead and other potential neurotoxic agents in the environment on the developing central nervous system as well as on different types of peripheral nerves in the adult. In one experimental protocol, defined areas of the fetal rat brain are grafted to the anterior chamber of the eye of adult rat recipients that are exposed to lead. Such grafts will become vascularized from the host iris and continue developing in oculo. Thus, grafted brain tissue and host brain will share circulation and therefore be exposed to similar amounts of lead. Studies of cerebellar grafts revealed that, although there was a normal gross cytological development in the presence of lead, there was a marked and permanent impairment of spontaneous discharge rates of the grafted Purkinje neurons as observed with electrophysiological techniques long after cessation of lead treatment. The host Purkinje neurons were not affected. A similar, although less dramatic, impairment of cerebellar function could be subsequently demonstrated in intact animals when newborn rats were given lead during the first 20 days of life and studied as adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗