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T J Collier

Publications and source records attributed to T J Collier.

69 records · Page 4Linked to original sources
PubMed1986

Survival and growth of fetal catecholamine neurons transplanted into primate brain.

Dopamine and norepinephrine neuroblasts of the ventral mesencephalon, hypothalamus, and dorsolateral pons were transplanted from fetal African green monkeys into multiple brain sites in adult (host) African green monkeys. Tissue was grafted from both early and late gestational age fetuses. Immunohistochemical analysis, with antibodies to tyrosine hydroxylase, a marker of catecholamine-containing neurons, showed large numbers of transplanted catecholamine neurons in host cerebral cortex, corpus striatum and lateral ventricles up to 69 days after transplantation. Serial reconstructions revealed extensive outgrowth of neuronal processes from large numbers of transplanted neurons as well as expansion of the size of transplanted (solid) grafts of fetal brain tissue in the host brain. Some grafts extended from the caudate nucleus into the adjacent lateral ventricles or from the cerebral cortex into the underlying corpus callosum and ventricle. There were dense networks of varicose fibers emanating from the tyrosine hydroxylase positive neurons within intraparenchymal and intraventricular grafts. The size and shape of transplanted neurons retained characteristics common to catecholaminergic neurons from the dissected regions of fetal brain. Thus, a variety of fetal, catecholamine-containing neurons survive transplantation to primate brain and produce extensive neuritic outgrowths. Moreover, rejection of transplanted tissue was not apparent. These findings provide essential information on nerve cell grafting in a species closely related to humans as a prerequisite in the consideration of neural transplants as therapeutic measures in neurological disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Neural transplantation: a review of recent developments and potential applications to the aged brain.

Mammalian neural transplantation has recently been recognized to be a valuable technique for studying normal development and regeneration in the central nervous system. In addition, the ability of grafted neurons to reinnervate damaged regions of the host brain and to ameliorate some neuroendocrine deficits, cognitive disorders and motoric dysfunctions in young adult rodents has suggested that transplantation therapy may be effective in treating human neurodegenerative diseases and neurotransmitter deficiencies related to aging. It is of particular interest that initial studies of neuron transplants in aged rodents indicate that cholinergic, dopaminergic and noradrenergic neurons all integrate to some extent with the aged brain, and that the product of this graft-host interaction is improved behavioral performance of aged subjects. The present paper critically reviews the present domain of neural transplantation, its application to studies on the properties of the aged mammalian brain and discusses the possible therapeutic use of transplants in ameliorating transmitter-specific abnormalities associated with Parkinson's disease and Alzheimer's disease.

Adrenal Medulla↗
PubMed1984

Selective impairment of declarative memory following stimulation of dentate gyrus granule cells: a naloxone-sensitive effect.

Albino rats received 10 s of sub-seizure electrical stimulation applied to the dentate gyrus granule cells immediately after acquisition of information on trial 1 of a 2-trial radial maze spatial memory task. Granule cell stimulation selectively reduced the probability of accessing information held in declarative memory ('knowing that' a particular maze location contains food) while leaving procedural memory intact ('knowing how' to search for food in the maze). This specific memory impairment was prevented by pretreatment with the opiate antagonist naloxone. Naloxone also improved memory performance when given to non-stimulated subjects.

Animals↗
PubMed1984

Electrical self-stimulation of dentate gyrus granule cells.

Male albino rats implanted with a chronic stimulating electrode electrophysiologically guided into the granule cell layer of the dorsal dentate gyrus were tested in a self-stimulation paradigm. It was found that subjects self-administer electrical stimulation to the granule cells at low, steady rates. Consistent with the presence of opioid-like immunoreactivity in the granule cell mossy fiber pathway, intraperitoneal injection of the opiate antagonist naloxone diminishes granule cell self-stimulation in a dose-related fashion. The results suggest that a granule cell opioid synapse participates in expression of reward at this site.

Animals↗
PubMed1982

Topography between the entorhinal cortex and the dentate septotemporal axis in rats: I. Medial and intermediate entorhinal projecting cells.

Retrograde tracing experiments were performed to clarify the topographic projection from medial (area 28m) and intermediate (area 28i) divisions of the entorhinal cortex to the dentate gyrus. Pipets filled with horseradish peroxidase (HRP) were positioned by electrophysiologic guidance at one of several septotemporal (S-T) levels in the dentate molecular layer of anesthetized rats; the tracer was expelled iontrophoretically to minimize its spread. Retrograde labeling of neurons within areas 28m and 28i was analyzed in relation to cytoarchitectonic as well as spatial features of the region (obtained by histologic reconstruction). Regardless of the S-T level, ejections of HRP which were confined to the dentate gyrus labeled only layer II neurons of each area. Following septal pole ejections, labeled neurons were located in the posterolateral, extreme posterior, and posteromedial parts of both areas 28m and 28i. Mid S-T ejections produced not only a ventral, but also an anteromedial, shift in the location of entorhinal projection cells; no cells were labeled posterolaterally. After temporal dentate ejections labeled neurons occupied the most anteromedial part of these entorhinal areas. For both areas, but especially for area 28i, convergence of entorhinal efferents upon a single S-T level in the dentate gyrus occurred from neurons which lay in a dorsoventral (i.e., frontal), and to a lesser extent a rostrocaudal, plane. The efferent axes of both areas 28m and 28i thus appear to be curved and are therefore best described in three dimensions. The entorhinal axes begin in a posterodorsolateral location, wrap around the posterior cortical convexity, and end in an anteroventromedial position. The results provide a useful map for in situ exploration of entorhinodentate connections in the rat, emphasize the parallel innervation of the dentate gyrus by distinct entorhinal fiber systems, and reflect the importance of the S-T axis as a framework for interpreting hippocampal organization.

Animals↗
PubMedDate not supplied

Decreased sympathetic innervation of spleen in aged Fischer 344 rats.

Splenic noradrenergic innervation in young adult and aged Fischer 344 rats was examined using fluorescence histochemistry for catecholamines and high performance liquid chromatography with electrochemical detection (LCEC) for the quantitation of norepinephrine (NE). In young adult rats, abundant noradrenergic plexuses followed the vasculature and trabeculae into splenic white pulp. In aged rats, noradrenergic innervation was reduced in density and in overall intensity of fluorescence, and splenic NE levels were significantly lower. The relationship between diminished noradrenergic innervation and diminished immune responsiveness in aging mammals, while not clear on a causal level, is presented as a hypothesis for further testing.

Aging↗
PubMedDate not supplied

Divergence of biological and chronological aging: evidence from rodent studies.

Literature on aging populations of rodents supports the intuitive view that significant functional variation exists among like-aged, elderly individuals: chronological age as a solitary measure is a poor indicator of biological age. In this report, we review a variety of studies which classify aged rodents based on genetic and/or behavioral similarities, in addition to chronological age, and have provided valuable neurobiological and physiological information on age-related changes which accompany functional impairments, or the lack of them. Beyond their descriptive value for gerontological research, these findings suggest ways in which biological aging can be manipulated to promote good function in aged individuals.

Aging↗
PubMedDate not supplied

Subpopulations, sites of interaction and therapy.

This commentary discusses the utility of behaviorally defined subpopulations of aged rodents as improved models of senescent memory dysfunction, the potential involvement of central norepinephrine systems in memory modulation, and the therapeutic outlook for age-related memory deficits.

Aging↗
PubMedDate not supplied

Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys.

Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxylase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would "toenails and talcum powder" do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0-2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by "blinded" observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A "parkinsonian summary score" derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with "early" (< 4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and "later" (> 14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Metabolic energy capacity of dopaminergic grafts and the implanted striatum in parkinsonian nonhuman primates as visualized with cytochrome oxidase histochemistry.

Histochemistry for visualization of the mitochondrial enzyme cytochrome oxidase has been detect cellular and regional differences in brain metabolism. We have examined the pattern of cytochrome oxidase (CO) staining in grafts of embryonic ventral mesencephalic tissue, and in the implanted striatum, of MPTP-treated monkeys as one index of the functional activity of grafted tissue and its influence on the host brain. Four monkeys were selected for study based on interesting variations in dopamine (DA) neuron content of their bilateral grafts as demonstrated with tyrosine-hydroxylase (TH) immunocytochemistry. The results suggest that grafts rich in DA neurons increase the metabolic activity of the implanted striatum of DA-depleted monkeys, and that this improvement of local energy metabolism is greater in the vicinity of grafts containing greater numbers of DA neurons. In addition, the pattern of CO staining within tissue transplants indicates that DA neurons exhibit the highest rate of metabolic activity among all cell types contained in the ventral mesencephalic grafts, and that the transplants receive metabolically active innervation from outside or within the grafted tissue.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Intrastriatal grafts from multiple donors do not result in a proportional increase in survival of dopamine neurons in nonhuman primates.

We examined the potential for "double grafts," i.e., grafts from two donors in each recipient, to enhance the total number of ventral mesencephalic dopamine neurons that survive grafting in adult African green monkeys. Because dopamine cell survival in grafts represents a small percentage of the total number of neurons grafted, several human clinical trials recently have employed grafts of tissue from multiple donors (e.g., from two to eight embryos per host recipient) in attempts to increase the total number of dopamine neurons that survive in grafts. Presumably, this is intended to elevate dopamine levels by providing more dopamine neurons to the damaged brain to alleviate the symptoms of parkinsonism. While well-developed grafts with several thousand dopamine neurons were found in most recipient animals, we observed a reduced total number of tyrosine hydroxylase positive neurons in the grafts in spite of the presence of some double grafts that were larger than normal. The overall growth of the grafts was impressive; some grafts were so large that they spanned the full dorsoventral extent of the caudate nucleus, probably reflecting the fact that twice as much tissue was implanted in each drop site in comparison to our standard protocol. However, some animals revealed atypical patterns of neurite outgrowth that appeared limited to the grafted tissue, and at least one monkey revealed "amorphous" grafts generally lacking in cellular structure, which suggests a possible rejection phenomenon. These findings raise questions about the use of multiple donors and suggest that the likelihood of rejection and/or cell death may be enhanced, which is of potential importance in the design of grafting strategies for clinical applications.

Animals↗