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Biomedical subjects

A Seiger

Publications and source records attributed to A Seiger.

At least 145 records · Page 8Linked to original sources
PubMed1983

Localization of nerve growth factor-like immunoreactivity in rat nervous tissue.

The use of immunofluorescence with affinity-purified antibodies enabled cytological localization of nerve growth factor-like material in the rat. Immunoreactivity was observed along various nerve tracts of the foetal rat brain and spinal cord at day 15 of gestation. Longitudinal pathways in ventral and dorsal spinal cord, ventral lower brain stem, posterior commissure, retroflex fascicle and in the olfactory bulb were all positive. A weaker and more widely spread immunostaining was visible in many areas in the central nervous system. Cranial nerves were strongly immunoreactive. Neuronal perikarya in the retina and the olfactory mucosa as well as filae olfactoriae and the olfactory nerve all the way to the olfactory bulb were also positive. In sensory ganglia and peripheral nerves most immunoreactivity was confined to supporting tissues, probably including Schwann cells. In irides, the pattern of immunoreactivity was similar to that of the sensory and autonomic innervation. More intensively fluorescent material was found in regrowing nerve fibres in iris transplants. Our histochemical results suggest that nerve growth factor and/or a related protein is present in large amounts along nerve pathways in supportive tissues of the peripheral nervous system as well as in the central nervous system during early development.

Animals↗
PubMed1983

Cerebellar Purkinje neuron hypoexcitability induced by chronic perinatal lead exposure.

The effects of perinatal lead administration on developing rat brain were studied by using cerebellar grafts in oculo. With 1% lead acetate in the drinking water, little change was seen in the histological organization of the graft. In marked contrast, virtually all Purkinje cell spontaneous discharge was absent in these grafts. This was seen even though 4-5 months had elapsed between the recording and the cessation of lead treatment. There was no alteration in electrophysiological properties of transplant Purkinje cells from sodium acetate-treated animals. Moreover, host in situ cerebellar Purkinje cells in both groups of animals discharged normally. These data indicate that lead administration, to elicit blood levels of 450-550 micrograms/liter, produces a long-lasting selective electrophysiological deficit in developing brain in oculo.

Action Potentials↗
PubMed1982

Intraocular development and adrenergic innervation of cortical and subcortical brain areas: influence of thyroid hormone deficiency.

Various immature brain regions have been isolated by grafting to the anterior chamber of the eye of adult recipients. The role of thyroid hormones for the growth of these isolated brain areas as well as their morphological maturation and adrenergic innervation in the eye have been investigated by surgical thyroidectomy of adult recipients prior to the intraocular brain grafting. Cortex cerebri showed a donor stage correlated thyroid hormone dependency so that 18-day donor fetuses gave rise to larger cortex grafts, whereas full-term donor fetuses resulted in smaller cortex grafts in thyroidectomized hosts. Brain stem showed an overall enhanced intraocular growth in thyroidectomized recipients, whereas both cerebellum and hippocampus did not seem to be influenced in oculo by a thyroid hormone deficiency. The morphological maturation of cortex cerebri grafts showed no alterations in thyroidectomized hosts as judged from light microscopy and cresyl violet staining. The density of sympathetic adrenergic nerves innervating the cortex cerebri grafts from the host iris was reduced by 50% in thyroidectomized hosts. This was parallelled by a reduction in noradrenaline concentration in cortex cerebri grafts in the experimental groups. Thus, the reduced number of nerves visible with Falck-Hillarp histochemistry in cortex cerebri grafts during thyroid hormone deficiency probably corresponds to a true reduction in adrenergic innervation. The present report points to a number of regionally as well as temporally selective effects on brain maturation and neuronal interaction of severe thyroid hormone deficiency.

Animals↗
PubMed1982

Prenatal ontogeny of neurons with enkephalin-like immunoreactivity in the rat central nervous system: an immunohistochemical mapping investigation.

Immunohistochemical techniques were used to describe the presence of endogenous levels of enkephalin-like immunoreactivity (ELI) in the developing central nervous system of the rat up until birth. The appearance and prenatal ontogeny of nerve cell bodies, nerve fiber pathways and varicose terminal plexuses expressing ELI were thus mapped using the indirect fluorescence immunohistochemical technique and fluorescein- and rhodamine-conjugated second antisera. ELI was first observed in beaded fibers along the midline from ventral pons to cervical spinal cord by prenatal day 15. Fluorescence could not be observed in the brains of 14 day old fetuses, although the adrenal medulla did show ELI at this stage. ELI-positive cell bodies at prenatal day 18 were found in most areas in which they have previously been described in adult rats. Many of the cells observed at prenatal day 18 were, however, not seen in untreated full term fetuses with the techniques used here. ELI-positive fibers and terminal fields begin to approach adult distributions at prenatal day 21--22. Several ELI-positive axon pathways which have not been previously reported from adult or developing brain, such as e.g. pathways in medial neocortex, in fasciculus retroflexus, in tractus mammillothalamicus, between ventral hypothalamus and globus pallidus and between ventromedial pons and the locus coeruleus area, are described. Semischematic maps are presented which outline all ELI-positive material as seen in sagittal projections of the central nervous system of 15 day, 18 day and full term fetuses. Maps of representative transverse sections of the full term brain are also included.

Animals↗
PubMed1982

Differential ethanol sensitivity of intraocular cerebellar grafts in long-sleep and short-sleep mice.

The relative importance of extrinsic and intrinsic factors for the differential sensitivity of Purkinje neurons in long-sleep (LS) and short-sleep (SS) lines of mice was investigated using cerebellar grafts to the anterior chamber of the eye. Cerebellar anlagen from fetal LS and SS donors survive and mature in oculo when grafted within and across lines. Mature cerebellar transplants from all four groups contained Purkinje cells that show sustained spontaneous discharge; excitation and inhibition are readily evoked by electrical stimulation of the surface of the graft. Superfusion of ethanol into the anterior chamber depresses Purkinje cell discharge, but neurons from LS donors are approximately 1 order of magnitude more sensitive than SS neurons; this differential sensitivity is unaltered by the host recipient line used. These data strongly suggest that the differential sensitivity of Purkinje cells to ethanol in the LS and SS mouse lines is an intrinsic property of the cerebellum.

Action Potentials↗
PubMed1982

Intraocular fibre growth of grafted locus coeruleus neurons: sensory denervation counteracts alterations induced by thyroid hormone deficiency.

Immature central noradrenaline neurons from the nucleus locus coeruleus were grafted to surgically thyroidectomized adult rats. As previously reported, fibre production from locus coeruleus in the host iris is hampered by thyroid hormone deficiency. We wanted to investigate if sensory denervation of the target iris tissue, a procedure known to enhance fibre production from locus coeruleus neurons, would interact with and possibly reverse the morphological signs of thyroid hormone deficiency. We found that a sensory denervation of the host iris reversed all morphological signs of the endocrine manipulation. Thus the number of axons found in bundles increased 30-fold and the density of accumulations intermingled with the fluorescent nerve plexus fell by half. Furthermore, the distribution of fibres in the host iris changed, spreading to more than double the surface area of the control thyroidectomized group. In all these respects the fibre growth of locus coeruleus in the sensorily denervated group mimicked what has been reported before in similarly denervated animals with intact endocrine status. These results show that the hampered nerve fibre growth induced by a thyroid hormone deficiency can be counteracted by a specific sensory denervation of the target tissue restituting the endocrine imbalance.

Animals↗
PubMed1981

Thyroxin dependency of the developing locus coeruleus. Evidence from intraocular grafting experiments.

Surgical thyroidectomies were used as means of altering the thyroid state of adult recipients to study the possible influence of thyroid hormones on fibre formation in irides by immature noradrenaline neurons of the locus coeruleus grafted to the eye. Whole-mount preparations of irides were analysed using fluorescence histochemistry according to Falck-Hillarp, subjectively estimating on a 'blind' basis the number of fibres, their pattern of distribution and individual morphology in the iris dilator plate. Neurones of the locus coeruleus formed nerve fibres in irides of thyroidectomized recipients to the same extent as in controls. Distribution and fine structure of these fibres, however, differed markedly. The numerous thick axon bundles from the attachment of the brain graft, normally seen to radiate out from locus coeruleus-neurones in oculo, were almost totally lacking in the thyroidectomized group. Also, the individual nerve fibres showed abundant peripheral accumulations of fluorescent material. This appearance of the outgrowth of fluorescent fibres in the experimental group, indicative of a disturbed formation of nerve fibres during development in oculo, was abolished by reversal of the thyroid hormone deficiency using daily injections of l-thyroxin to the recipients throughout the experiment. This strongly indicates a role for thyroxin in the process of formation of nerve fibres originating from the neurones of the locus coeruleus during perinatal development. The present paper is supportive of recent reports claiming that during the development of the CNS thyroxin plays a crucial role in tubulin assembly, and thus presumably for the ability of neurones to form processes.

Animals↗
PubMed1981

Thyroid hormone dependency in immature but not mature grafted locus coeruleus neurons. Evidence from intraocular innervation of iris transplants.

Fetal brain tissue pieces containing locus coeruleus noradrenaline neurons were combined with sequentially or simultaneously grafted irides in the anterior eye chamber of thyroidectomized or normal host rats. The aim was to reveal possible morphological alterations in the adrenergic fibres innervating the iris grafts, induced by thyroid hormone deficiency, and to compare that possible hormone dependency with what has been found before in host irides innervated by locus coeruleus neurons. Nerve fibre outgrowth was evaluated in iris whole mounts, using Falck Hillarp fluorescence histochemistry. The distribution of locus-coeruleus-derived fibres on host irides was markedly altered in the thyroidectomized hosts. The number of fluorescent axon bundles was significantly decreased, and the intermingled varicose nerve fibre plexus contained numerous accumulations of fluorescent material. In the iris grafts from normal or thyroidectomized hosts reinnervated by matyured locus coeruleus neurons there was no difference in distribution or morphology between the two groups. This clearly shows that matured locus coeruleus neurons are not thyroid hormone dependent during a reinnervation process, after the stimulus elicited by a sensory denervation of iris. When immature locus coeruleus neurons were made to innervate iris grafts by simultaneous grafting of brain tissue and an iris to the eye a clearly reduced number of axon bundles was formed in the iris grafts of the thyroidectomized group. The morphological discrepancies between the two groups were, however, markedly smaller for iris grafts than for corresponding host irides. This might indicate that the potent growth stimulus elicited by sensory denervation of irides partly counteract the inhibition of axon bundle formation by immature grafted locus coeruleus neurons in irides during thyroid hormone deficiency.

Adrenergic Fibers↗
PubMed1980

Nerve growth factors in the rat iris.

Nerve growth factor (NGF) activity was not detected by bioassay in irides killed immediately after excision but NGF appeared within 24 h in living irides placed in culture or grafted to a host eye. Furthermore, sensory and, although less effective, sympathetic denervation of irides in situ led within 10 days to the appearance of NGF activity. In addition, freezing and thawing released a parasympathetic neuronotrophic factor activity from irides.

Animals↗
PubMed1980

Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long-term behavioral, biochemical, and histochemical studies.

Motor deficits produced in rats by unilateral substantia nigra lesions have been found to be reduced by grafts of fetal rat substantia nigra to the dopamine denervated caudate nucleus. In the present study these grafts were examined behaviorally, histochemically, and biochemically over six to 10-month periods. The grafts were found to survive in a healthy condition and contain catecholaminergic cells and fibers after eight to ten months. Concentrations of dopamine in adjoining parts of the caudate nucleus were increased when examined six months after grafting. Apomorphine induced rotation was reduced by the grafts, and these reductions persisted for at least six months. Although signs of aging were observed in the brains of the host animals when sacrificed eight to ten months after grafting, the grafts remained healthy and showed no signs of aging or deterioration. It is concluded that substantia nigra grafts can become permanent, functional constituents of the brains of host animals with prior substantia nigra lesions.

Animals↗
PubMed1980

Conditions for adrenergic hyperinnervation in hippocampus: I. Histochemical evidence from intraocular double grafts.

The developing hippocampal anlage of rats was homologously grafted to the anterior chamber of the eye of adult recipients. After intraocular maturation of the hippocampal graft and removal of the sympathetic innervation of the eye by ipsilateral superior cervical ganglionectomy, four types of monoamine neurons were transplanted to the eye chamber: Peripheral sympathetic neurons, central adrenergic neurons of locus coeruleus, central dopaminergic neurons of substantia nigra, and central 5-hydroxytryptamine neurons of the lower raphe nuclei. All four classes of monoamine neurons were able to reinnervate the hippocampal graft, but the fiber ingrowth differed markedly. Although peripheral sympathetic neurons produced a pattern of adrenergic innervation in the hippocampal graft which resembled innervation of the hippocampus by the locus coeruleus in the brain, locus coeruleus neurons themselves produced an extremely dense plexus of fibers within the graft. This hyperinnervation remained intact for up to 9 months, the longest period of time studied. The locus coeruleus graft itself received fibers from the hippocampus graft, as demonstrated by the retrograde transport of horseradish peroxidase. We conclude that the hippocampal graft exerts a much stronger growth stimulation on the locus coeruleus neurons than on the peripheral sympathetic neurons. The difference between innervation patterns suggest that both presynaptic and postsynaptic influences determine fiber ingrowth in the central nervous system.

Adrenergic Fibers↗
PubMed1980

Conditions for adrenergic hyperinnervation in hippocampus: II. Electrophysiological evidence from intraocular double grafts.

Following sequential intraocular transplantations of areas containing NE cell bodies (locus coeruleus or superior cervical ganglion) and of NE fiber target areas (hippocampus), both pieces mature in a manner analogous to that observed for individual transplants. NE-containing nerve fibers, derived from either LC or SCG transplants, can be seen to invade the hippocampal formation. When LC is used, the invading fibers markedly hyperinnervate the hippocampus while SCG-derived fiber densities approximate those seen with innervation from the adrenergic ground plexus of the iris. Electrophysiological recordings from neurons in the LC reveal an atropine-sensitive excitatory response to illumination, suggesting innervation of the LC by cholinergic nerve fibers from the iris. This is supported by the fact that dense cholinesterase-positive staining can be found in the LC piece. Application of an epileptogenic agent, such as penicillin, results in a marked excitation of neurons in the LC without inducing epileptiform activity in the hippocampus. In contrast, single hippocampal grafts seize readily after penicillin. Local application of the inhibitory agent GABA into the LC allows penicillin-induced epileptiform activity to generate in the hippocampus, suggesting that functional inhibitory innervation develops between NE fibers derived from LC and pyramidal neurons in the hippocampus. Supporting this, subsequent excitation of LC neurons by iontophoresis of glutamate terminates the hippocampal seizure. Prior administration of reserpine (2.5 mg/kg) disrupts the inhibitory influence of LC innervation on the hippocampal EEG following penicillin. After reserpine, the hippocampal portions of double grafts behave like single hippocampal transplants. It is concluded that sequential transplantations of cell body and target regions of the CNS to the anterior chamber of the eye creates a functional, yet isolated, neuronal pathway which can be utilized to study the development of neuronal connections.

Adrenergic Fibers↗