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Biomedical subjects

G J Harry

Publications and source records attributed to G J Harry.

At least 55 records · Page 3Linked to original sources
PubMed1992

Acrylamide exposure preferentially impairs axonal transport of glycoproteins in myelinated axons.

The right L5 dorsal root ganglion of adult rats exposed to acrylamide (40 mg/kg body weight/day for nine consecutive days) was injected with either [3H]methionine or [3H]glucosamine. After allowing incorporation into macromolecules and axonal transport to proceed for 5 hr, the distribution of radioactivity in cross sections and longitudinal sections of sciatic nerve was determined by autoradiography. Control and treated animals showed no difference in distribution of label within the sciatic nerve with respect to rapidly transported proteins labelled with [3H]methionine. In control animals the distribution of rapidly transported glycoproteins labelled with [3H]glucosamine was similar to that found for [3H]methionine-labelled proteins. In contrast, acrylamide-exposed rats had a very different distribution of labelled glycoproteins; there was a marked paucity of label in the myelinated axons. We interpret this result as indicating that acrylamide preferentially inhibits glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons.

Acrylamide↗
PubMed1989

Colchicine-induced alterations in receptor-stimulated phosphoinositide hydrolysis in the rat hippocampus.

Intradentate administration of colchicine has been reported to affect the cholinergic muscarinic system in the hippocampus, causing a reduction in quinclidinylbenzilate binding sites and an increase in choline acetyltransferase activity. Since the cholinergic muscarinic system is coupled to the formation of inositolphosphates in the brain, the effect of intradentate administration of colchicine on the agonist-induced turnover of inositollipid was studied in rats. The animals were sacrificed 12 weeks after injection, and the hippocampi removed and sliced. [3H]Inositol was incorporated into slices in the presence of lithium, and carbachol, a cholinergic muscarinic receptor agonist, was used to study the stimulated turnover of inositollipids. Hippocampal slices taken from colchicine-treated rats showed an increased carbachol-stimulated accumulation of inositolmonophosphate. Thus, intradentate colchicine appears to alter the signal transduction process for the muscarinic cholinergic receptor in the hippocampus, a change that may be associated with compensatory processes following damage to the hippocampus.

Animals↗
PubMed1989

Acrylamide-induced increases in deposition of axonally transported glycoproteins in rat sciatic nerve.

The axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve was examined in adult rats exposed to acrylamide via intraperitoneal injection (40 mg/kg of body weight/day for nine consecutive days). The L5 dorsal root ganglion was injected with either [35S]methionine to label proteins or [3H]glucosamine to label, more specifically, glycoproteins and gangliosides. At times ranging from 2 to 6 h later, the sciatic nerve and injected ganglion were excised and radioactivity in consecutive 5-mm segments determined. In both control and acrylamide-treated animals, outflow profiles of [35S]methionine-labeled proteins showed a well defined crest which moved down the nerve at a rate of approximately 340 mm/day. Similar outflow profiles and transport rates were seen for [3H]glucosamine-labeled glycoproteins in control animals. However, in animals treated with acrylamide, the crest of transported labeled glycoprotein was severely attenuated as it moved down the nerve. This finding suggests that in acrylamide-treated animals, axonally transported glycoproteins were preferentially transferred (unloaded or exchanged against unlabeled molecules) from the transport vector to stationary axonal structures. We also examined the clearance of axonally transported glycoproteins distal to a ligature on the nerve. The observed impairment of clearance in acrylamide-treated animals relative to controls is supportive of the above hypothesis. Acrylamide may directly affect the mechanism by which axonally transported material is unloaded from the transport vector. Alternatively, the increased rate of unloading might reflect an acrylamide-induced increase in the demand for axonally transported material.

Acrylamide↗
PubMed1989

Tellurium-induced neuropathy: metabolic alterations associated with demyelination and remyelination in rat sciatic nerve.

Rats fed a diet containing 1.25% elemental tellurium initiated on postnatal day 20 undergo a transient neuropathy characterized by synchronous demyelination of peripheral nerves. In sciatic nerve, the extent of demyelination was maximal after 5 days of tellurium exposure; there was a loss of 25% of the myelin, as assayed by concentration of myelin-specific P0 protein. Tellurium-induced alterations in the metabolic capacity of Schwann cells were examined by measuring the synthesis of myelin lipids in vitro in isolated sciatic nerve segments. Exposure to tellurium resulted in an early marked decrease of approximately 50% in overall incorporation of [14C]acetate into lipids, with a preferential depression in synthesis of cerebrosides, cholesterol, and ethanolamine plasmalogens (components enriched in myelin). Most dramatically, within 1 day of initiation of tellurium exposure, there was a profound increase in [14C]acetate-derived radioactivity in squalene; 23% of incorporated label was in this intermediate of cholesterol biosynthesis, compared to less than 0.5% in controls. In association with the remyelinating phase seen after 5 days of tellurium exposure, synthesis of myelin components gradually returned to normal levels. After 30 days, metabolic and morphologic alterations were no longer apparent. We suggest that the sequence of metabolic events in sciatic nerve following tellurium treatment initially involves inhibition of the conversion of squalene to 2,3-epoxysqualene, and that this block in the cholesterol biosynthesis pathway results, either directly or indirectly, in the inhibition of the synthesis of myelin components and breakdown of myelin.

Acetates↗
PubMed1988

Ganglioside interactions with the dopaminergic system of rats.

The effects of ganglioside treatment on changes in dopaminergic function following 6-hydroxydopamine (6-OHDA) or repeated exposure to haloperidol were studied in male Fischer-344 rats. Rats were injected sc with 30 mg/kg of a mixed ganglioside preparation (GM) at the time of the surgery and for 13 days after receiving an intranigral injection of 6-OHDA. GM treatment attenuated 6-OHDA depletion of striatal dopamine (DA) and DOPAC. Another group of rats was implanted with chronic indwelling cannulas in the lateral cerebroventricles at the time of 6-OHDA administration into the substantia nigra. Daily intraventricular injection of 25 or 50 micrograms GM attenuated depletions of striatal DA and DOPAC. A separate experiment sought to determine the effects of GM1 on the development of receptor supersensitivity produced by repeated exposure to a dopamine receptor antagonist. Rats were injected sc with 1 mg/kg haloperidol for 8 or for 16 days; some rats were coadministered 20 mg/kg GM1 sc. Four days after the last dose, the rats were challenged with 1 mg/kg apomorphine, and activity was counted for 60 min. Treatment with GM1 decreased the behavioral supersensitivity to apomorphine induced by repeated exposure to haloperidol. These experiments suggest that treatment with GM can have a protective effect against 6-OHDA-induced depletion of dopamine if treatment with GM begins at the time of lesioning. These studies also support receptor binding data from other laboratories indicating that treatment with GM1 can affect up-regulation of dopamine receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Role of dentate gyrus cells in retention of a radial arm maze task and sensitivity of rats to cholinergic drugs.

Male adult Fischer-344 rats that received bilateral injections of colchicine into two rostrocaudal sites showed relatively long-lasting alterations in the performance of a previously acquired radial arm maze task and specific destruction of dentate granule cells. Results of subsequent experiments with cholinergic drugs indicated that physostigmine or nicotine had no effect on the number of errors made in the maze, although other signs of cholinergic or pharmacological activity were present. RS-86, an analog of the muscarinic agonist arecoline, decreased errors in colchicine-treated rats, but these effects were associated with signs of parasympathetic overstimulation and behavioral sedation. Pretreatment with scopolamine, a muscarinic cholinergic receptor antagonist, increased errors in control rats but had no effect in colchicine-treated rats. Results of subsequent experiments found that colchicine-treated rats were less sensitive to the motor stimulant effect of scopolamine. These effects appeared to be associated with increased levels of choline acetyltransferase in the hippocampus and a down regulation of muscarinic postsynaptic receptors. One interpretation of these data is that intradentate colchicine may destroy granule cells, which leads to a compensatory reinnervation of cholinergic nerve terminals having cell bodies in the septum.

Acetylcholine↗
PubMed1987

Time-dependent neurobiological effects of colchicine administered directly into the hippocampus of rats.

Rats were given bilateral injections of colchicine into the dorsal and ventral hippocampus. Behavioral, neurochemical and histopathological measurements were taken, up to 12 weeks after surgery. Colchicine produced a consistent increase in spontaneous motor activity, enhanced acoustic startle reactivity, and accelerated acquisition of two-way shuttle box avoidance, but did not affect reactivity to a noxious thermal stimulus. Measurement of dynorphin in the hippocampus indicated that colchicine rapidly depleted this neuropeptide, which is thought to be contained preferentially in the mossy fibers of granule cells of the hippocampus. Colchicine also decreased Met-enkephalin in the hippocampus, but the magnitude of the change (22%) was less than that (89% depletion) observed for hippocampal dynorphin. Examination of hippocampal morphology using light microscopic techniques indicated that colchicine caused approximately 60% degeneration of granule cells in the hippocampus. Although the length of the pyramidal cells was decreased (12-16%), the width of the CA1 and CA3 region of the hippocampus was not affected. These data underscore the importance of the granule cells in the mediation of behavioral processes such as motor activity, startle reactivity and performance of shuttle box avoidance.

Acoustic Stimulation↗
PubMed1987

Experiential factors in the expression of hypermotility produced by intradentate colchicine: lack of effect of GM1 ganglioside on colchicine-induced loss of granule cells and mossy fibers.

Adult male Fischer-344 rats were given bilateral injections of 2.5 micrograms colchicine or artificial cerebrospinal fluid into caudal and rostral sites of the dentate gyrus of the hippocampus. One group of rats received 21 consecutive daily injections of 20 mg/kg GM1 gangliosides, i.p., beginning the day prior to surgery. Another group received saline. Colchicine-induced hypermotility was not seen in animals repeatedly handled 21 d after surgery, in spite of significant decreases in granule cell number and decreases in the volume of hippocampal mossy fibers. Pretreatment with GM1 had no effect on behavior and it did not protect against the hippocampal damage produced by colchicine. Rats given colchicine, but not handled for 21 d, showed significant hypermotility, which was associated with decreases in hippocampal granule cells. These data underscore the importance of handling in postlesion functional recovery.

Animals↗
PubMed1987

Axonal transport characteristics of gangliosides in sensory axons of rat sciatic nerve.

The distribution of axonally transported gangliosides and glycoproteins along the sciatic nerve was examined from 3 h to 4 weeks following injection of[3H]glucosamine into the fifth lumbar dorsal root ganglion of adult rats. Incorporation of labeled precursor into these glycoconjugates reached a maximal level in the ganglion within 6 h. Outflow patterns of radioactivity for glycoproteins showed a well-defined crest with a transport rate of approximately 330 mm/day. In contrast, the crest of transported gangliosides was continuously attenuated, implying a significant deposition along the axon, and an alternative method of calculating velocity was required. Analysis of accumulation of labeled material at double ligatures demonstrated both anterograde and retrograde transport of glycoproteins and gangliosides and allowed for the calculation of an anterograde transport rate of about 270 mm/day for each. Additional evidence of ganglioside transport is provided in that the TLC pattern of transported radioactive gangliosides accumulating at a ligature is significantly different from the pattern seen in the dorsal root ganglion or following intraneural administration of the labeled precursor. These data indicate that gangliosides are transported at the same rapid rate as glycoproteins but are subject to a more extensive exchange with stationary material than are glycoproteins.

Animals↗
PubMed1986

Pharmacological modification of DDT-induced tremor and hyperthermia in rats: distributional factors.

Pretreatment of rats with hydantoin (75 mg/kg, PO, an anticonvulsant), trihexyphenidyl (10 mg/kg, SC, a muscarinic cholinergic antagonist), or piperonyl butoxide (500 mg/kg, PO, a metabolic inhibitor) had no effect on the whole blood or brain tissue levels of orally administered DDT (75 mg/kg) or its metabolites DDD and DDE. Hydantoin and piperonyl butoxide decreased DDT-induced tremor and hyperthermia due to DDT when measured 12 h after DDT exposure, while trihexyphenidyl augmented some components of DDT-induced tremor. Additional experiments found that pretreatment with piperonyl butoxide increased tremor due to permethrin exposure (120 mg/kg, PO), while having no effect on tremor due to chlordecone administration (60 mg/kg, IP). Pretreatment with ellipticine (30 mg/kg, IP, a metabolic inhibitor) also decreased tremor 12 h after DDT exposure. The effects of piperonyl butoxide and ellipticine on DDT-induced tremor are postulated to occur through direct actions of these compounds on nerve or muscle tissue. Hydantoin-induced attenuation of DDT-induced neurotoxicity may be due to the ability of hydantoin to block repetitive firing of nerves by binding to the inactivation gates of sodium.

Animals↗
PubMed1985

The effect of lead toxicity and milk deprivation of myelination in the rat.

During a defined postnatal developmental period, the 2nd through the 28th postnatal day, rats were exposed daily to either an oral administration of 200 mg lead (as lead acetate) per kilogram of body weight, an 8-hr maternal milk deprivation schedule, or a combination of the two insults. On the 29th day the rats were killed. Either lead exposure or milk deprivation alone decreased brain (10%) and body (15%) weights, and an additive effect was observed in rats exposed to both lead and milk deprivation (brain: 20%; body: 35%). Neither the lead nor the deprivation insult alone produced a perturbation in the process of myelination. However, when the two conditions were combined an interaction was evident as a 25% decrease in myelin accumulation in females. No effect was seen in males. The myelination deficit in females was specific in that neither accumulation of glial fibrillary acidic protein (a marker for astroglial cells) nor neurofilament protein (a marker for neurons, especially axons) was perturbed. Tissue lead concentrations did not suggest that this increased sensitivity in females was due to a selective increase in their body burden of lead.

Animal Nutritional Physiological Phenomena↗
PubMed1985

The use of Synapsin I as a biochemical marker for neuronal damage by trimethyltin.

The content of Synapsin I (Protein I) was examined in brain regions of adult rats exposed to trimethyltin (TMT), and in control animals. Long Evans hooded rats were intragastrically dosed with 4 mg TMT hydroxide/kg body weight for 4 days. No perturbations in Synapsin I levels were evident by 24 h following the fourth dose; however, by 36 h, a significant decrease of 28% in Synapsin I level was present in the hippocampus of TMT treated animals. This decrease was selective, no other brain region examined was affected. As determined by regional analysis of inorganic tin, this specificity was not due to a profound preferential accumulation of tin in the hippocampus. Despite the absence of an alteration in Synapsin I levels at 24 h, morphological examination revealed perturbation in the normal uniform arrangement of granule cell neurons, with dead neurons diffusely distributed throughout the facia dentata. At 36 h, these changes were only slightly more extensive. In contrast, examination of the terminal projection area of these cells, the mossy boutons, showed to be unaffected at 24 h after the 4th dose of TMT. However, by 36 h, many of the mossy boutons contained dense bodies and showed signs of degeneration. This result suggested that the loss of Synapsin I coincides with degeneration of the nerve terminal region. In order to better establish the temporal correlation, a less severe dosing regimen (only 3 days of exposure to 4 mg TMT/kg body wt) was utilized to attenuate the time course of necrosis. Again, necrotic changes were visible in the perikaryon by 1 day after termination of toxicant dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Effects of nicotine on the visual evoked response.

The effects of smoking cigarettes differing in nicotine content (0.14 vs 1.34 mg/cigarette) on the peak-to-peak amplitude and peak latency of the human averaged visual evoked response (AVER) were measured in 10 male smokers after a 2-hr smoking deprivation period. The AVER was obtained under five different flash intensities. Eight different peaks were involved in the amplitude and latency measurements. The nicotine dosage and flash intensity factors both had significant effects on peak-to-peak amplitudes while only the flash intensity factor affected peak latencies. The general enhancement of peak-to-peak amplitudes by the 1.34 mg cigarette, relative to the 0.14 mg cigarette, indicates that the effects of cigarette smoking on the AVER are predominantly due to nicotine's psychopharmacologic action, as opposed to other elements in tobacco smoke or as opposed to nonpharmacologic mechanisms involving learning processes. Past research, on an electrophysiological and behavioral level, indicating that nicotine, as administered via cigarette smoking, may have enhancing and/or restorative effects on visual attentional processes in the quiescent smoker was supported.

Adult↗
PubMed1982

Postpartum exposure to triethyl tin produces long-term alterations in responsiveness to apomorphine.

Male and female rat pups were exposed to a single dose of triethyl tin (TET) or ethanol vehicle on day 5 postnatally and tested for responsiveness to apomorphine as adults. TET-exposed animals displayed an increased response to the stereotypic effects of 1 mg/kg of apomorphine. Female rats exposed neonatally to TET had decreased baseline rates of responding on a food reinforced variable interval (VI) 15 sec. schedule, while TET-exposed males were found to have increased baseline rates relative to controls. The rats maintained on a VI 15 sec. schedule were given various doses of apomorphine (0.0312-0.25 mg/kg, s.c.). Neonatal exposure to TET had no effect on the disruptive effects of apomorphine on VI 15 sec. responding. These data show an altered responsiveness of TET-exposed animals to higher doses of apomorphine (1 mg/kg), but not to lower doses of apomorphine (0.0312-0.25 mg/kg). The present data are in accord with the hypothesis that one of the long-term consequences of neonatal exposure to TET might be an alteration in the responsiveness of the dopamine system.

Animals↗
PubMed1981

The effects of postpartum exposure to triethyl tin on the neurobehavioral functioning of rats.

Male and female Fischer rat pups received sc injections of 1.5 or 3 mg/kg of triethyl tin bromide (TET), ethanol vehicle or distilled water on day 5 postpartum. At 21, 28, 60, and 90 days of age, the rats were weighed and assessed in a battery of tests which included fore- and hindlimb grip strength, negative geotaxis, startle responsiveness and spontaneous motor activity. Animals at 60 days of age were also tested in a two-way shuttle box avoidance procedure. Exposure to TET did not affect body weight at any time during testing, nor did it affect negative geotaxis of grip strength, Startle response to an air puff stimulus was decreased in males and females at 21 and 60 days of age, while no effects were observed at 28 or 90 days of age. Responsiveness to an acoustic stimulus was decreased at 60 days of age only. Spontaneous motor activity of males was increased at 21, and 28 and 60 days of age, while females had elevated activity at 28 and 60 days of age. Relative to ethanol controls, rats of both sexes were significantly hypoactive at 90 days of age. In a two-way shuttle box procedure, latencies to emerge prior to the first trial were elevated in TET exposed male and female rats. The number of discriminated avoidance responses made during a 60 trial session was decreased in females receiving the 3 mg/kg dose. Activity during the intertrial interval was not affected. A single postnatal exposure to TET can produce long-term alterations in the sensorimotor capabilities of rats; the effect appears to occur equally in both sexes and is independent of toxicant-induced body weight changes.

Aging↗
PubMed1977

Morphine and methadone-induced antinociception in rats permanently depleted of brain dopamine.

The purpose of the present study was to evaluate the role of brain norepinephrine (NE) and/or dopamine (DA) in the production of the antinociceptive effects of morphine and methadone. Rats were permanently depleted of brain NE and/or DA via 6-hydroxydopamine (6-OHDA) treatments at two weeks of age. Six to eight weeks later, the antinociceptive activity of morphine and methadone was determined in control, NE and DA-depleted, and DA-depleted rats by tail-flick methods. Both dose-response and time-duration studies were conducted. The data obtained suggested that DA was important to morphine, but not to methadone-induced antinociception. However, this relationship appeared contingent upon the level of DA-depletion. An antagonism of morphine's effects was observed when DA levels were down by at least 85% whereas a facilitation of morphine's effect occurred when DA levels were 50% or less. These findings were discussed in relation to more recent concepts suggesting that: 1) DA-related behaviors are contingent upon a balance between excitatory and inhibitory DA neuron pools, and 2) antinociception may (in relation to DA) also be controlled via a balance between this system (DA) and NE systems. Thus, it was suggested that the potency of morphine's antinociceptive effects appears contingent upon a balance between one or more of these neuron pathways.

Analgesics↗