Biomedical subjects

G J Harry

Publications and source records attributed to G J Harry.

59 records · Page 4Linked to original sources

PubMedDate not supplied

Sensitivity of adenosine triphosphatases in different brain regions to polychlorinated biphenyl congeners.

Polychlorinated biphenyl (PCBs) mixtures contain a number of different congeners, some of which have been proposed to be neuroactive. Recent studies have suggested that ortho-substituted PCBs may be neuroactive, while 'dioxin-like' non-ortho-substituted congeners are not. This study compared the in vitro effects of a putative neuroactive ortho-biphenyl (2,2'-dichlorobiphenyl; DCBP) with that of a putative non-neuroactive congener lacking ortho-chlorine substitutions (3,3',4,4',5-pentachlorobiphenyl; PCBP) on Mg(2+)-ATPase activity in mitochondrial and synaptosomal preparations from striatum, hypothalamus, cerebellum and hippocampus. In these studies, DCBP significantly inhibited oligomycin-sensitive (OS) Mg(2+)-ATPase activity in all four brain regions in a concentration-dependent manner; PCBP, on the other hand, had no effect on OS Mg(2+)-ATPase activity in any brain region examined at concentrations up to 100 microM. The striatum, a dopamine-rich region, was not preferentially sensitive to the effects of DCBP. Furthermore, DCBP did not inhibit synaptosomal Na+/K(+)-ATPase activity, suggesting a specificity of action on OS Mg(2+)-ATPase. These data support previous structure-activity relationships, suggesting that ortho-substituted PCB congeners are neuroactive while non-ortho-substituted congeners are not. Disruption of mitochondrial oxidative energy production may play a role in the neuroactivity of ortho-chlorinated PCBs.

Animals↗

PubMedDate not supplied

Acrylamide-induced alterations in axonal transport. Biochemical and autoradiographic studies.

Alterations in the axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve were examined in adult male rats exposed to acrylamide (40 mg ip/kg body wt/d for nine consecutive days). Twenty-four hours after the last dose, the L5 dorsal root ganglion (DRG) was injected with either [35S]methionine to label proteins or [3H]glucosamine to label glycoproteins and gangliosides. The downflow patterns of radioactivity for [35S]methionine-labeled proteins and [3H]glucosamine-labeled gangliosides were unaltered by acrylamide treatment. In contrast, the outflow pattern of labeled glycoproteins displayed a severely attenuated crest with no alteration in velocity, suggesting a preferential transfer with the unlabeled stationary components in the axolemma. Retrograde accumulation of transported glycoproteins and gangliosides was unaltered for at least 6 h; however, by 24 h, there was a 75% decrease in the amount of accumulated material. The accumulation of [35S]methionine-labeled proteins was not altered. Autoradiographic analysis revealed an acrylamide-induced paucity of transported radiolabeled glycoproteins selectively in myelinated axons with no effect on "nonmyelinated" axons. The pattern of transported proteins was similar in both control and acrylamide-exposed animals. These results suggest a preferential inhibition of glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons. More importantly, it suggests that interpretations of axonal transport data must be made with the consideration of alterations in selective nerve fibers and not with the tacit assumption that all fibers in the nerve population are equally affected.

Acrylamide↗

PubMedDate not supplied

Induction of tumor necrosis factor alpha in cultured glial cells by trimethyltin.

Within the central nervous system, cytokines are thought to play an active role in pathophysiological changes seen in various neurodegenerative diseases and trauma. Previous studies in our laboratory demonstrated that systemic administration of the neurotoxicant trimethyltin (TMT) produced a rapid and sustained elevation of CNS TNF alpha mRNA levels. In order to examine the effects of TMT on glial cultures in the absence of a neuronal component, primary glial cultures were exposed to TMT. Cultured glial cells undergo distinct morphological changes within 6 h of exposure to 10 microM TMT. This is characterized by an initial retraction of astrocytic processes revealing long, thin GFAP-dense processes and enlarged cell bodies, progressing to distinct retraction of plasmalemmna processes by 24 h. Prior to morphological changes, mRNA levels for the astrocyte-specific protein, glial fibrillary acidic protein (GFAP), increased within 3 h, as determined by Northern blot hybridization. Approximately a four-fold increase in TNF alpha mRNA levels was observed after 6 h as determined by competitive RT-PCR. This stimulation resulted in a 10-fold increase in the biologically active form of TNF alpha protein. These results suggest that a direct stimulation of glial cells may produce an early and critical response of the nervous system in chemical-induced neurotoxicity.

Animals↗

PubMedDate not supplied

Pfiesteria toxin and learning performance.

Pfiesteria piscicida is an estuarine dinoflagellate involved with fish kills along the east coast of the United States. We previously documented a radial-arm maze learning deficit in rats exposed to Pfiesteria that may be related to cognitive deficits seen in humans after accidental Pfiesteria exposure. The current study elucidated important behavioral parameters of this deficit. There were six dose groups. Forty (10/group) adult female Sprague-Dawley rats were injected (s.c.) with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600, 106,800, or 320,400 Pfiesteria cells/kg of rat body weight or a cell-free filtrate of the 106,800 cells/kg dose). One control group (N = 10) was injected with saline and one (N = 10) with aquarium water not containing Pfiesteria. Half of the rats in each group were tested on an 8-arm radial maze in a standard test room, and the other half were tested on the radial maze in a sound-attenuating chamber. In the standard maze room, there was a significant effect of Pfiesteria (p < 0.05) impairing choice accuracy improvement over the first six sessions of training among rats administered 106,800, 320,400, and the 106,800 cells/kg filtered sample. In contrast, there was no indication of an effect of Pfiesteria when the rats were tested on the same configuration radial maze in the sound-attenuating chamber. After 18 sessions of training in one room, the rats were switched for six sessions of testing in the other room and finally were switched back to their original room for three sessions. There was a significant Pfiesteria-induced deficit when the rats were tested in the standard test room but not when they were tested in the sound-attenuating chamber. When the Pfiesteria-exposed rats were initially switched from the sound-attenuating chamber to the standard test room they performed significantly worse than controls, whereas Pfiesteria-treated rats switched from the standard test room to the sound-attenuating chamber did not perform differently from controls. These results suggest that the Pfiesteria-induced learning impairment may result from the negative impact of distracting stimuli. At the time of the learning impairment, no overt Pfiesteria-related effects were seen using a functional observational battery and no overall response latency effects were seen, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the initial use of the figure-8 maze in this line of research, the rats in the same Pfiesteria treatment groups that showed significant deficits in the radial-arm maze showed greater declines in activity rates in a 1-h figure-8 locomotor activity test. Both the 106,800 and 320,400 Pfiesteria cells/kg groups showed significantly greater linear trends of activity decline relative to tank water-treated controls. This reflected an initial slight hyperactivity in the Pfiesteria-treated animals followed by a decrease to control levels. Pfiesteria effects in the figure-8 maze and in early radial-arm maze training may be useful in a rapid screen for identifying the critical toxin(s) of Pfiesteria in future studies.

Animals↗

PubMedDate not supplied

Glycine modulates the toxicity of benzyl acetate in F344 rats.

The influence of supplemental glycine on benzyl acetate (BA; a compound metabolized via the hippurate pathway)-induced toxicity was investigated. Groups of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000 ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000 ppm BA and 27,000 ppm glycine or 50,000 ppm BA 32,000 ppm L-alanine; supplemental glycine and L-alanine were equimolar. The L-alanine group served as an amino nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and served as an untreated isonitrogenous control BA caused increase in mortality, body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the cerebellum, hippocampus, and pyriform cortex of the brain. These effects were reduced significantly by supplementation with glycine but not with L-alanine. These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity.

Air Pollutants, Occupational↗