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R B Gibbs

Publications and source records attributed to R B Gibbs.

51 records · Page 3Linked to original sources
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↗
PubMed1987

Effects of entorhinal lesions on trophic activities present in rat entorhinal cortex and hippocampus as studied using primary cultures of entorhinal and septal tissues.

The present study examined trophic activities in normal and injured brain which affect the survival and growth of central neurons in culture. Adult rats received bilateral lesions through the angular bundle, severing projections between the entorhinal cortex and the hippocampus. Ten days later, extracts were prepared from the entorhinal or hippocampal regions of the injured brains and compared with extract prepared from analogous regions of normal brains for trophic activities in cultures of either entorhinal or septal tissues. At least three activities were observed: (1) a trophic activity which bound to polylysine-treated wells, which was greater than 10,000 Da in size, heat labile, and sensitive to trypsin, and which supported the survival of both septal and entorhinal neurons in culture; (2) a trophic activity which did not bind to polylysine-treated wells, which was greater than 10,000 Da in size, heat labile, and sensitive to trypsin, and which, in the presence of polylysine-bindable material, facilitated the survival and growth of entorhinal cells in culture, and (3) an inhibitory activity which significantly reduced survival in entorhinal cultures when cells were plated in the presence of high concentrations of extract prepared from normal brain. These effects were not due to nonspecific effects of plating the cells in, or treating the wells with, large amounts of protein. A significant injury-related increase in non-polylysine-bindable trophic activity was also observed. Extracts prepared from either the hippocampus or the entorhinal area of the injured brains contained more non-polylysine-bindable trophic activity than extract prepared from normal brains. Injury-related changes in trophic activities were more prominent in entorhinal than in septal cultures. This increase in activity may account for the injury-related effects on the survival of entorhinal transplants reported previously [Gibbs and Cotman: Neuroscience (in press) 1987], and may represent an endogenous mechanism by which the brain attempts to selectively support the survival of injured cells following injury.

Animals↗
PubMed1987

Entorhinal transplants and spatial memory abilities in rats.

Transplants of embryonic entorhinal tissues, placed into the angular bundle region of adult rats, innervate appropriate areas of the host hippocampal formation and amygdala, provided that native entorhinal connections have been destroyed. In the present study, transplants were examined for their ability to restore spatial memory abilities which are lost following the bilateral destruction of native entorhinal connections. Animals were tested for their ability to perform an 8-arm radial maze task, for spontaneous alternation in a T-maze, and for their ability to learn to alternate in a T-maze for a food reward. Animals with lesions, and those with lesions + implants, remained impaired on all 3 tasks examined for as long as 6 months postimplantation. During this time, no transplant-induced behavioral recovery was observed, although behavioral stabilization was observed on the spontaneous alternation task at 6 months post-transplantation. The data suggest that these transplants may be limited in their ability to restore functions which are highly dependent upon the anatomical integrity of the damaged circuits and the precise organization of information flow through the damaged area.

Amygdala↗
PubMed1987

Factors affecting survival and outgrowth from transplants of entorhinal cortex.

The purpose of this study was to examine injury-related effects on the survival and growth of entorhinal tissues transplanted to the adult rat entorhinal area. Embryonic entorhinal cortex was transplanted to the angular bundle region of adults either immediately, or 8-10 days, after severing specific host projections. Graft survival (Nissl stain) and connectivity (acetylcholesterase stain and retrograde labeling with wheat germ agglutinin-horseradish peroxidase) were examined two months post-transplantation. Grafts transplanted 8-10 days after severing the angular bundle were large and contained many cells which innervated the hippocampal formation. Grafts transplanted immediately after severing the angular bundle were small, did not integrate well with the host tissues, and failed to innervate the hippocampal formation. Grafts transplanted without producing any prior lesion, or following lesions which did not damage host entorhinal projections, were intermediate in size, but failed to innervate the hippocampal formation. The data demonstrate that: (1) introducing a delay between the lesion and implant surgeries can significantly enhance graft survival and the establishment of transplant-to-host projections, and (2) transplant-derived innervation of the host is significantly impaired when host homologous fibers are intact. These findings suggest that environmental factors, induced specifically by the destruction of host homologous fibers, are responsible for the differences in transplant survival and connectivity observed.

Animals↗
PubMed1986

Factors affecting innervation in the CNS: comparison of three cholinergic cell types transplanted to the hippocampus of adult rats.

Embryonic septal, striatal and habenular tissues were transplanted to adult hippocampi from which the native septal input had been removed. Cholinergic innervation of the host hippocampal formation was observed with each type of transplant. The pattern of innervation was comparable to the native cholinergic projection, suggesting that transmitter type is correlated with the pattern of innervation produced regardless of the origin of the innervating cells. The grafts differed, however, in their survival, their propensity to innervate the host, and the degree of innervation they produced.

Acetylcholinesterase↗
PubMed1986

Transplantation of septal neurons maintained in long-term culture.

Septal cells were maintained in culture for varying lengths of time and then transplanted to adult hippocampi from which the native septal input had been removed. Cells grafted after 1 week in culture survived transplantation to the brain and innervated the host hippocampus in a pattern comparable to the native cholinergic projection. Cells grafted after 2 weeks in culture did not survive in the brain, but did survive re-plating. In addition, the viability of cells transplanted from culture paralleled the viability of brain tissue taken from donors of equivalent ages, suggesting that changes which occur in culture and affect the viability of transplanted neurons may also occur during normal development.

Acetylcholinesterase↗
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

Lack of correlation between cortical levels of choline acetyltransferase and learning scores in rats with globus pallidus lesions.

Previous work has shown that rats with lesions of the globus pallidus (GP) exhibit a generalized learning impairment. Data are presented suggesting that this impairment is not due to inadvertent damage to the nucleus basalis magnocellularis. Rats with GP lesions evidenced a significant visual discrimination learning loss and a significant reduction in cortical choline acetyltransferase (ChAT) activity. However, there was no significant correlation between the severity of the learning loss and the amount of reduction of cortical ChAT activity.

Animals↗
PubMed1986

Learning deficits in rats with early neurotoxic lesions to the globus pallidus, substantia nigra, median raphe or pontine reticular formation.

Previous studies have shown that weanling rats with electrolytic lesions of the globus pallidus (GP), substantia nigra (SN), median raphe (MR) or pontine reticular formation (PRF) are deficient in learning a wide variety of laboratory tasks. The current study was designed to investigate whether this nonspecific learning deficiency is due to destruction of cells intrinsic to these subcortical regions or to fibers passing through these regions. Accordingly, neurotoxic lesions of the GP, SN, MR or PRF were made in weanling rats using ibotenic acid. Rats were subsequently required to learn a visual discrimination, a 3-cul maze and a nonvisual (incline plane) discrimination. While those groups with GP, SN or MR lesions showed significant deficits on all three problems, only the animals with GP lesions exhibited deficits comparable in magnitude to those associated with corresponding electrolytic lesions. Animals with lesions to the PRF were impaired only on the nonvisual discrimination. These results suggest that while destruction of neurons alone within the GP, SN or MR can produce a nonspecific learning impairment, the combined destruction of neurons and fibers of passage within the SN, MR or PRF produces a more profound learning deficit.

Animals↗
PubMed1985

Replacement of damaged cortical projections by homotypic transplants of entorhinal cortex.

The extent to which transplants of embryonic cortical tissue can be used to replace damaged cortical projections has been examined. Embryonic entorhinal cortex was implanted into the entorhinal region of young adult rats that had previously received a lesion through the angular bundle. Projections between transplant and host were examined by using WGA-HRP and the fluorescent dye Fast Blue. Implants selectively innervated areas of the host hippocampus and amygdala which normally receive entorhinal afferents. Implants were innervated by cells in the host diagonal band and, in one case, by cells in the contralateral entorhinal and/or presubicular cortex. In most cases, host fibers were differentially distributed within transplants, possibly reflecting an ability of host fibers to recognize and selectively innervate their appropriate targets even though the cellular organization of the implant is different from that present during normal development. These data suggest that homotypic implants of embryonic entorhinal cortex can, in some ways, replace severed cortical projections and may eventually be able to reconstitute normal cortical circuitry.

Amidines↗
PubMed1984

Enhancing the self-repairing potential of the CNS after injury.

Embryonic CNS tissues can now be successfully transplanted into most regions of the CNS in neonate, adult, or aged host animals. The transplants generally project to their correct target areas in the host brain. However, transplants appear to receive only partial innervation by host fibers. Replacement of lost host neurons by transplants has proven to be functionally most successful in the cases of neurosecretory, monoaminergic, or cholinergic neurons. Their success probably depends on their ability to deliver the proper neurotransmitter (and perhaps trophic factors) close to their targets rather than on their capacity to reestablish all lost connections. Efforts to achieve complete integration of the transplants will probably require interventive strategies to guide the natural repair response of CNS tissue. Survival and outgrowth of the transplants can be promoted by taking advantage of the natural increase of neurotrophic factors in response to injury. Neurotrophic factors and substrate guidance factors, once purified and completely characterized, promise to be powerful new therapeutic agents for enhancing the survival and regrowth of the injured CNS.

Age Factors↗
PubMed1975

Epidermolysis bullosa acquisita with electron microscopical studies.

Epidermolysis bullosa acquisita (EBA), one of the rare, scarring, nonhereditary, mechanobullous diseases, occurred in a 74-year-old woman. Clinical histological, and immunofluorescent findings are comparible with those previously reported in cases of EBA. To our knowledge, this is the first report of electron microscopical studies in EBA. Electron microscopy of "normal-looking" skin with EBA shows a noncellular, amorphous material on the dermal side of the basal lamina. Electron microscopy of slightly traumatized skin with EBA is very similar to that seen in dermolytic bullous dermatosis.

Aged↗
PubMed1975

Multiple minute digitate hyperkeratoses.

A 56-year-old man had multiple minute digitate hyperkeratosis. His clinical and histological findings are compatible with those of the only other case reported in the literature.

Biopsy↗
PubMedDate not supplied

Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats.

Female Sprague-Dawley rats were ovariectomized at 13 months of age. Four groups received different regimens of estrogen or estrogen plus progesterone replacement beginning either immediately, 3 months, or 10 months after ovariectomy and were compared with non-hormone-treated controls. Eight to twelve months after ovariectomy, animals were trained on a delayed matching-to-position (DMP) spatial memory task. Long-term treatment with estrogen or estrogen plus progesterone significantly enhanced acquisition of the DMP task by aged animals after long-term loss of ovarian function. Weekly administration of estrogen and progesterone was at least as effective as, if not more effective than, continuous treatment with estrogen alone. In addition, treatment initiated 3 months, but not 10 months, after ovariectomy was as effective at enhancing DMP acquisition as continuous estrogen treatment initiated immediately after ovariectomy, suggesting a window of opportunity after the loss of ovarian function during which hormone replacement can effectively prevent the effects of aging and hormone deprivation on cognitive function. These findings suggest that repeated treatment with estrogen and progesterone initiated within a specific period of time after the loss of ovarian function may be effective at preventing specific negative effects of hormone deprivation on brain aging and cognitive decline.

Aging↗