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K J Anderson

Publications and source records attributed to K J Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1990

Autoradiographic characterization of putative excitatory amino acid transport sites.

Removal of excitatory amino acids from the extracellular space is now postulated to occur through at least two distinct transport systems that are distinguished by their ionic dependency. Thus, both sodium-dependent and chloride-dependent systems have been described in the mammalian central nervous system. In this report we attempt to characterize these sites by autoradiography, using D-[3H]aspartate and L-[3H]glutamate as ligands. Previous studies have shown that sequestration of radioligand into membrane vesicles can be a potential artifact when examining transport sites. We have found that sequestration can be alleviated by incubation of tissue sections in xylenes prior to incubation with radioligand. Using in vitro autoradiography we have characterized the two binding sites with respect to their distribution, kinetics and pharmacology. Both appeared to have a single, saturable binding site with Kds in the low micromolar range. Sodium-dependent D-aspartate binding predominated, having a Bmax that was five times greater than chloride-dependent L-glutamate binding in whole brain. The levels of binding to the two sites varied between brain regions. Sodium-dependent D-aspartate binding was highest in the cerebellar molecular layer greater than dentate gyrus molecular layer greater than entorhinal cortex. Chloride-dependent L-glutamate binding was highest in the outer layers of cerebral cortex greater than dentate gyrus molecular layer greater than entorhinal cortex greater than striatum. Pharmacological characterization of these sites also showed major differences. Sodium-dependent D-aspartate binding was most potently inhibited by L-aspartate greater than threo-beta-hydroxyaspartate greater than L-cysteine sulfinic acid greater than L-cysteic acid. Chloride-dependent glutamate binding was most potently inhibited by L-glutamate greater than L-alpha-amino adipic acid greater than quisqualate greater than L-serine-o-sulfate. The differences in distribution, ligand binding properties and pharmacology of these sites suggest that a significant variable in excitatory amino acid circuitry may include heterogeneity in transporters associated with excitatory pathways.

Amino Acids↗
PubMed1990

Neuronal structure of the lacertilian parietal eye, I: A retrograde label and electron-microscopic study of the ganglion cells in the photoreceptor layer.

The cellular connectivity of the lacertilian parietal eye is not well understood. Because the intercellular connections establish the foundation for information processing, we have investigated cellular connectivity of one cell type in this simple vertebrate retina. We also developed an in vitro preparation to study the anatomy of the parietal eye visual system. Horseradish peroxidase transport in the in vitro preparation revealed a class of displaced ganglion cells occupying positions among the photoreceptors, in a location where the presence of interneurons had been suggested. Three-dimensional reconstruction at the electron-microscopic level showed that the morphology and synaptic input of these displaced ganglion cells is different from that of the previously known ganglion cells. The displaced ganglion cells receive an average of about 13 ribbon synapses from photoreceptors. The ribbon input is equally distributed between the soma and dendritic arbor. Junctional membrane measurement and ethanolic phosphotungstic acid-staining provided evidence for the existence of non-ribbon synaptic contacts (synaptoid junctions). Displaced ganglion cells make about 20 synaptoid junctions, 65% of which are on the dendritic arbor. The morphology of the displaced ganglion cell is such that a significant measure of synaptic input to the dendritic arbor will be transmitted to the soma.

Animals↗
PubMed1989

Elevated environmental temperature enhances immunity in experimental Chagas' disease.

C3H mice are highly susceptible to the Brazil strain of Trypanosoma cruzi. These mice usually die during the acute phase of infection and develop a profound immunosuppression to heterologous and parasite antigen. In this study, we confirmed earlier reports that infected mice maintained at elevated environmental temperature (36 degrees C) are significantly more resistant to T. cruzi than are mice kept at 20 to 24 degrees C. To determine whether the benefits of increased environmental temperature were due to alterations in the host immune system, the production of antibody to heterologous antigen and the development of parasite-specific T-helper cells were examined in noninfected and T. cruzi-infected mice. Mice were immunized with either sheep erythrocytes (SRBC) or trinitrophenyl groups (TNP) conjugated to fixed culture forms of T. cruzi, and the splenic direct plaque-forming cell (DPFC) responses to SRBC and to TNP-conjugated SRBC were determined. The DPFC response to SRBC from infected mice maintained at elevated environmental temperature was much higher than the suppressed response of infected mice held at room temperature and slightly higher than the response of age-matched noninfected control mice. Likewise, maintaining infected mice at 36 degrees C significantly enhanced the parasite-specific responses of T-helper cells, as reflected by anti-TNP DPFC responses of mice immunized with TNP-conjugated TC.

Animals↗
PubMed1988

GABA as a potential transmitter in lizard photoreceptors: immunocytochemical and biochemical evidence.

The retina of the desert night lizard, Xantusia vigilis, was examined for immunoreactivity to antibodies against gamma-aminobutyric acid and L-glutamate decarboxylase. At the electron microscopic level it was found that a distinct population of the photoreceptor cells was immunoreactive to both antibodies. Computer-assisted reconstruction of serial sections positively identified the immunoreactive receptors as cones. These cones constituted 15% of the photoreceptors in the retinal sections, and they were morphologically distinct. The mean diameter of the labeled cone synaptic pedicles was 5.8 micron whereas that of the unlabeled pedicles was 7.9 micron, a statistically significant difference. L-glutamate decarboxylase was extracted from the lizard brain, positively identified radiometrically, and shown by immunodiffusion to crossreact with the antibody used for localization. The authors suggest that the immunoreactive cones synthesize and accumulate gamma-aminobutyric acid. Whether or not it is used by those cones as a neurotransmitter should be tested directly.

Animals↗
PubMed1988

Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo.

Cutting the axons of the cholinergic neurons that project to the hippocampal formation results in death of most of these cells. Previous studies have shown that administration of nerve growth factor before or at the same time as the lesion will prevent this cell death. Here we demonstrate that basic fibroblast growth factor (FGF) administered into the brain reduces the death of cholinergic neurons in the medial septum and diagonal band of Broca after transection of their axons, in both young adult and aged rats. Moreover, FGF can partially protect against death of cholinergic neurons even when administered two days after axonal transection. These results indicate a possible function for FGF in the normal support of basal forebrain cholinergic neurons, but its range of activity could be wider, for FGF also supports noncholinergic neurons in vitro, it is localized in many of the central nervous system neurons, and it is found in relatively high concentrations in the brain.

Animals↗
PubMed1988

Transmitter phenotype is a major determinant in the specificity of synapses formed by cholinergic neurons transplanted to the hippocampus.

Embryonic habenular or striatal cholinergic tissues were transplanted to the hippocampal formation of adult rats. The connectivity of these grafts with the host hippocampal formation was analysed using acetylcholinesterase histochemistry and immunocytochemistry with a monoclonal antibody to choline acetyltransferase. Both graft types produced laminar arrangements of acetylcholinesterase-positive fibers in the hippocampal formation that closely resembled the native pattern of cholinergic innervation. In addition, graft-derived choline acetyltransferase-immunoreactive synapses were found in the host hippocampal formation. These synapses were formed on non-immunoreactive dendritic structures and were similar to the types of cholinergic synapses found in the hippocampal formation of normal animals. These data indicate that the cholinergic transmitter phenotype is a major determinant of whether a neuron will form typical cholinergic synapses with hippocampal targets.

Acetylcholinesterase↗
PubMed1988

Synaptic plasticity and functional stabilization in the hippocampal formation: possible role in Alzheimer's disease.

In this chapter we have explored the hypothesis that reactive synaptogenesis is an adaptive mechanism that can compensate for loss of a fraction of a defined neuronal population. Partial cell loss occurs during the course of aging, neurodegenerative diseases, and minor traumatic brain injuries. As cells are lost or as their function severely declines, new connections made by healthy neurons from within the population can assume parallel functions (homotypic sprouting), or fibers from converging pathways (heterotypic sprouting) can act to boost weakened signals and maintain functional stability. When cell death (or disease) progresses to the point where the pathway is broken, sprouting can no longer maintain information flow along the circuit and thus is unable to preserve function, unless new circuits can also be compensatory as, for example, after unilateral injury. We have analyzed the consequences of cell loss on the nature of circuit regrowth within the primary hippocampal circuits--i.e., the entorhinal-dentate gyrus-CA3-CA1 pathways. Reactive synaptogenesis can occur throughout the system after loss of each major cell population. Homotypic sprouting predominates in several pathways (e.g., dentate gyrus after CA4 loss, CA1 field after CA3 loss), and heterotypic sprouting appears prominent in the dentate gyrus after entorhinal cell loss. Each reactive network as a result of the regrowth can, in principle, still function, if cell loss is partial. The observation that sprouting also occurs in Alzheimer's disease illustrates that a slow and fractional loss of a neuronal assembly can trigger reactive growth in humans even along with a severe neurodegenerative disease. Axon sprouting was predicted in the dentate gyrus after entorhinal cell loss from rodent studies and has now been demonstrated in the brain of Alzheimer's victims. Cholinergic septal inputs, if present, can sprout, thereby enhancing cholinergic function and transmission by entorhinal perforant path fibers. CA4 fibers also sprout, thereby increasing positive feedback on granule neurons. At present, however, the functional significance of these mechanisms has yet to be established in clinical studies. Alzheimer's disease has a prolonged course with progressive symptoms. We would propose that axon sprouting or reactive synapse formation provides additional stability beyond the decline predicted from cell loss alone (Fig. 8). Thus, the clinical threshold where functions disappear is postponed for longer periods of time. Some reports in the literature are consistent with rapid behavioral decline followed by intervening periods of stability.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer Disease↗
PubMed1987

N-acetylaspartylglutamate identified in the rat retinal ganglion cells and their projections in the brain.

N-Acetylaspartylglutamate like immunoreactivity (NAAG-L) was identified in retinal ganglion cell bodies and their axons. The presence of the dipeptide in ganglion cell projection areas, the lateral geniculate nucleus (LGN) and superior colliculus (SC), was confirmed following NAAG purification from these tissues by a high-performance liquid chromatographic method. NAAG-L was identified in the optic tract as well as within fibers and puncta in the LGN and SC. The hypothesis that NAAG is present within ganglion cell axons in the brain was tested by unilateral enucleation which resulted in loss of NAAG and NAAG-L within the contralateral LGN and SC.

Animals↗
PubMed1986

Localization of N-acetylaspartylglutamate-like immunoreactivity in selected areas of the rat brain.

N-acetylaspartylglutamate (NAAG) was detected immunohistochemically in the rat brain using an antiserum which recognizes carbodiimide-fixed NAAG. NAAG-like immunoreactivity is described in 5 areas of the brain; olfactory bulb, septal nuclear area, lateral geniculate nucleus, superior colliculus and the entorhinal cortex/hippocampal formation. Mitral cells of the olfactory bulb and neurons concentrated in the medial septum were densely immunostained. A dense population of immunoreactive puncta was found in the superior colliculus and lateral geniculate nucleus (LGN). The LGN also contained immunoreactive neurons. The entorhinal cortex contained numerous immunoreactive cells in layers II-III while the hippocampus had few neurons that were NAAG-positive.

Animals↗
PubMed1986

Reactive synaptogenesis in hippocampal area CA1 of aged and young adult rats.

Selective lesions that result in a partial loss of neuronal input appear to signal residual, undamaged inputs to sprout and replace synaptic connections that have been lost. Previous investigations have compared this process of reactive synaptogenesis in young and old animals in the hippocampal dentate gyrus and have demonstrated that the aged brain has a diminished capacity for reinnervation following massive denervation of a target area. This investigation has focused on the lesion-induced plasticity of an adjacent area of the hippocampal formation, area CA1 of regio superior, in young adult and aged rats. Young adult aged Fischer 344 rates were subjected to a unilateral, intraventricular injection of kainic acid that selectively destroyed the CA3-CA4 hippocampal pyramidal neurons. Following a 2-day interoperative interval, the rats sustained an ipsilateral transection of the fimbria-fornix. Animals were killed at 4, 10, 30, and 60 days following the second transection and processed for electron microscopic analysis. Photographic montages were constructed of area CA1 extending from the alveus to the hippocampal fissure. The density of synapses, both intact and degenerating, was determined and analyzed as a function of age, days postlesion, and zone of analysis. Synaptic density decreased 30-40% contralaterally and 60-70% ipsilaterally in both aged and young adult rats. While both age groups restored synaptic density to preoperative levels, aged subjects required significantly more time. Aged rats appeared to be retarded in the initial phases of synaptic replacement. The delay in the aged animals' reactive response was not due to any differences in degeneration clearance between the age groups.

Aging↗
PubMed1986

Immunocytochemical localization of gamma-aminobutyric acid in the rat hippocampal formation.

gamma-Aminobutyric acid (GABA) was detected immunocytochemically in the rat hippocampal formation utilizing a new antiserum made against GABA conjugated to bovine serum albumin. GABA immunoreactivity was found to be concentrated in pericellular networks of fibers around both dentate granule and hippocampal pyramidal neurons. Ultrastructural analysis indicated that GABA-immunoreactive (IR) terminals most often contained small clear vesicles and made symmetrical contacts with somata and dendritic shafts of hippocampal neurons. In addition, numerous GABA-IR neurons resembled basket interneurons that have been described in previous reports.

Animals↗
PubMed1986

Ultrastructural characterization of identified cholinergic neurons transplanted to the hippocampal formation of the rat.

The ultrastructural features of cholinergic neurons transplanted to the rat hippocampal formation were studied by using a monoclonal antibody to choline acetyltransferase (ChAT). Septal cell suspensions were prepared from E-18 rat embryos and injected into the hippocampus of host rats that had been previously subjected to a bilateral transection of the fimbria-fornix. Rats with fimbria-fornix lesions alone and unoperated rats served as controls and were examined to characterize the native hippocampal cholinergic system. Both unoperated controls and rats with fimbria-fornix lesions showed a sparse population of intrinsic ChAT-immunoreactive neurons that were most numerous in the subgranular zone, the hilus fascia dentata, and near the hippocampal fissure. ChAT-positive terminals from controls formed synapses on dendritic structures that were primarily symmetrical. ChAT-positive dendrites in controls received synaptic input from nonimmunoreactive axon terminals. In rats with septal transplants, ChAT-immunoreactive transplant neurons were found that were either bipolar or multipolar. Axons of transplanted neurons were unmyelinated and arose either from the cell body or a primary dendritic process where they gave off numerous collaterals. Terminals from transplant neurons formed synapses with many nonimmunoreactive neurons. In transplant animals, two main targets of ChAT-immunoreactive terminals were identified: The great majority of synapses were symmetrical junctions with dendritic spines and shafts. A number of terminals were found that appeared to be juxtaposed to nonimmunoreactive axon terminals, possibly forming symmetrical axo-axonic connections. In contrast, such axo-axonic contacts were not observed in the controls. It is concluded that transplanted cholinergic neurons may reinnervate the host hippocampus; however, this reinnervation is different from what is seen in the intact hippocampal formation.

Animals↗
PubMed1986

Immunocytochemical localization of serotonin in the rat dentate gyrus following raphe transplants.

The ultrastructural features of the serotoninergic innervation of the rat dentate gyrus in normal adults and in animals receiving raphe nuclear area transplants was investigated using an antibody to serotonin (5-HT). Neonatal rats received a lesion of the fimbria-fornix and entorhinal cortex. Three days later, a portion of embryonic (E-16-18) raphe nuclear area was transplanted to the entorhinal cavity and the animals were allowed to survive for 60 days. Animals were processed for the immunocytochemical localization of 5-HT using the peroxidase-antiperoxidase method. Light microscopic observation showed that 5-HT-containing fibers from transplanted raphe neurons densely innervated the hilar and molecular zones of the dentate gyrus. Electron microscopic analysis showed that 5-HT immunoreactivity was contained only in axons and axon varicosities. There were no differences in the ultrastructural characteristics of axons and axon terminals between normal animals and those which had received raphe transplants. A mixture of both conventional synaptic junctions and non-synaptic axonal swellings were found in both groups.

Animals↗
PubMed1986

Altered regulation of lesion-induced synaptogenesis by adrenalectomy and corticosterone in young adult rats.

Quantitative electron microscopy was used to examine the effect of circulating glucocorticoids on the removal of degenerating synapses and the replacement of lost synaptic contacts in young adult rats that follow partial denervation of the hippocampal dentate gyrus. Subjects were adrenalectomized prior to subcutaneous implantation of pellets containing a specified concentration of corticosterone and subsequent unilateral ablation of the entorhinal cortex. Animals maintained at high circulating concentrations of glucocorticoids were significantly retarded in the early phase of degenerating synapse removal and in the rate of synaptic replacement. Subjects maintained at extremely low concentrations of glucocorticoids were also significantly retarded in the early stages of synapse removal but showed an early replacement of lost synaptic contacts followed by a dramatic decrease in the rate of replacement. By 60 days after the lesion both groups of animals showed synapse replacement equivalent to young adult controls while significant amounts of degenerating synapses still remained in the denervated neuropil. The results demonstrate that circulating glucocorticoids can exert a marked influence on lesion-induced synaptic replacement in the hippocampal dentate gyrus.

Adrenalectomy↗
PubMed1986

Senile plaques as aberrant sprout-stimulating structures.

In Alzheimer's disease, the cholinergic septal input to the dentate gyrus molecular layer appears to sprout, presumably in response to the loss of entorhinal input to this region. Neuritic plaques accumulated in regions of septal sprouting and were present in these regions to a much greater degree than in areas of no apparent sprouting. We suggest that the reactive sprouts participate in the pathogenesis of plaque formation. The stimulus for plaque formation may be sprouting induced by a focal accumulation of injury-induced trophic factors. The demonstration of sprouting in Alzheimer's disease indicates that the appropriate mechanisms are intact. Eventually, however, the fibers succumb to the pathogenic processes in the disorder.

Acetylcholinesterase↗
PubMed1985

Strain comparison of synaptic density in hippocampal CA1 of aged rats.

Synaptic density in hippocampal CA1 stratum radiatum was studied in two different strains of rat at 3 and 24-28 months of age. Neither Fischer 344 nor Sprague-Dawley rodents showed any age-related loss of synapses. These data support the contention that synapse loss with age is not a generalized phenomenon in the mammalian CNS.

Aging↗
PubMed1984

Variability in relationships of arteries and nerves in the human orbit.

Orbits of humans were examined by dissection to study anatomic relationships of selected arteries and nerves. The usual paths of the ophthalmic artery and nasociliary nerve were superior to the optic nerve, but the ophthalmic artery crossed inferior to the optic nerve in 28% of the cases, a higher incidence than generally reported. The anterior ethmoidal artery and nerve almost invariably passed between the superior oblique and medial rectus muscles. When present, the posterior ethmoidal artery and nerve generally coursed above the superior oblique muscle.

Adult↗