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PubMed1988

Molecular and cellular aspects of calcium action in plants.

Calcium is known to be a second messenger in many developmental processes in animal systems, but it has only recently become evident that Ca is an important intracellular messenger in plants as well. The level of free Ca concentration in the cytoplasm is extremely low, and it is influenced by extracellular signals such as light, gravity, and hormones. Investigations from our laboratory indicated that Ca and its binding protein, calmodulin, play an important role in stimulus-response coupling by regulating enzyme activities, especially through protein phosphorylation. In vivo and in vitro protein phosphorylation studies have revealed Ca-dependent changes in various plant tissues. We have also been able to influence various physiological processes such as cell elongation, abscission, senescence, and tuberization by altering extracellular and intracellular Ca levels. Other examples of Ca-mediated processes in plants are as follows: a) cell division, b) geotropism, c) protoplasmic streaming, d) stomatal control, e) chloroplast movement, f) secretion, g) hormone-dependent changes, h) enzyme activation, and i) protein phosphorylation.

Calcium↗

PubMed2005

Field application of a set of cellular biomarkers in the digestive gland of the freshwater snail Radix peregra (Gastropoda, Pulmonata).

An active biomonitoring study was performed in the vicinity of two pulp and paper mill effluents (PPMEs) released in two different streams in northeastern France. Freshwater gastropods, Radix peregra (=Lymnaea peregra or Lymnaea pereger), were transplanted for 0, 3, 14 and 21 days at two to three sites located upstream and downstream from the mill discharge points in both rivers. Lysosomal and peroxisomal systems, as well as lipofuscin and neutral lipids, were tested using histochemical methods on cryostat sections of digestive gland tissues, and stereological data were obtained by image analysis. Evidence of structural changes in the lysosomal system was found in animals exposed to both effluents, comprising general stress responses such as enlarged and more numerous lysosomes; and also possible specific pluri-phasic effects. Modifications of the lysosomal and cytoplasmic contents of lipid-related materials were also described, namely enhanced lipofuscin deposit and neutral lipid depletion. The peroxisomal proliferation in exposed snails seems to show its implication in oxidative stress detoxication, without preventing higher lipoperoxidation, as indicated by the increased amounts of digestive lipofuscin. Structural changes of the lysosomal and peroxisomal systems, digestive lipofuscin and neutral lipid contents have potential for use as early cellular biomarkers in Radix peregra exposed to environmental stressors, which deserve further investigations.

Analysis of Variance↗

PubMed2006

Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: a potentially difficult distinction resolved by cytokeratin 5/6.

The solid papillary variant of ductal carcinoma in situ is an uncommon entity, which usually presents in the seventh or eighth decade and may be associated with invasive mucinous carcinoma. Solid papillary ductal carcinoma in situ (SP-DCIS) shares many morphological features with usual ductal hyperplasia (UDH) involving a papilloma: papillary architecture, solid growth, cellular streaming, and low-grade nuclear features. These similarities can make the distinction between these 2 entities challenging. Recent studies have demonstrated that immunohistochemical staining for cytokeratin 5/6 can distinguish UDH from conventional forms of ductal carcinoma in situ. Most of the epithelial cells of UDH express cytokeratin 5/6, but the tumor cells of ductal carcinoma in situ do not. We tested the hypothesis that the results of staining for cytokeratin 5/6 can distinguish UDH from the solid papillary variant of ductal carcinoma in situ. Immunohistochemical staining of 14 cases of SP-DCIS and 9 cases of UDH (4 involving papillomas) was performed using cytokeratin 5/6 antibody clone D5/16 B4. Strong cytoplasmic or membrane staining was considered positive. The hyperplastic cells in all cases of UDH showed strong staining for cytokeratin 5/6. The percentage of positive cells ranged from 50% to 80%. None of the SP-DCIS tumor cells stained for cytokeratin 5/6; however, many cases did show staining of occasional entrapped, benign epithelial, and myoepithelial cells. We conclude that the absence of strong cytokeratin 5/6 expression by SP-DCIS distinguishes it from its morphological mimic, UDH. Pathologists must guard against misinterpreting SP-DCIS as UDH in those cases in which the carcinoma cells engulf cytokeratin 5/6-expressing residual, native epithelial cells.

Biomarkers, Tumor↗

PubMed2003

IUGR alters postnatal rat skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a fiber specific manner.

Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of insulin resistance in humans and rats. Aberrant skeletal muscle lipid metabolism contributes to the pathogenesis of insulin resistance. Peroxisome proliferator-activated receptor-gamma co-activator-1 (PGC-1) is a transcriptional co-activator that affects gene expression of key lipid metabolizing enzymes such as carnitine palmitoyl-transferase I (mCPTI). Because gene expression of lipid metabolizing enzymes is altered in IUGR postnatal skeletal muscle, and we hypothesized that PGC-1 expression would be similarly affected. To prove this hypothesis, bilateral uterine artery ligation and sham surgery were used to produce IUGR and control rats respectively. Western Blotting demonstrated that PGC-1 hind limb skeletal muscle protein levels were increased in perinatal and postnatal IUGR rats. Conventional RT-PCR demonstrated that PGC-1 mRNA levels were similarly increased in perinatal hind limb skeletal muscle and juvenile extensor digitorum longus (EDL), but were decreased in juvenile soleus. Because a gender specific trend was noted in PGC-1 mRNA levels, real time RT-PCR was used for further differentiation. Real time RT-PCR revealed that changes in postnatal skeletal muscle PGC-1 expression were more marked in male IUGR rats versus female IUGR rats. Down stream targets of PGC-1 followed a similar pattern of expression. We conclude that PGC-1 expression is altered in rat IUGR skeletal muscle and speculate that it contributes to the pathogenesis of insulin resistance in the IUGR rat.

Female↗

PubMed1994

Ponticulin is an atypical membrane protein.

We have cloned and sequenced ponticulin, a 17,000-dalton integral membrane glycoprotein that binds F-actin and nucleates actin assembly. A single copy gene encodes a developmentally regulated message that is high during growth and early development, but drops precipitously during cell streaming at approximately 8 h of development. The deduced amino acid sequence predicts a protein with a cleaved NH2-terminal signal sequence and a COOH-terminal glycosyl anchor. These predictions are supported by amino acid sequencing of mature ponticulin and metabolic labeling with glycosyl anchor components. Although no alpha-helical membrane-spanning domains are apparent, several hydrophobic and/or sided beta-strands, each long enough to traverse the membrane, are predicted. Although its location on the primary sequence is unclear, an intracellular domain is indicated by the existence of a discontinuous epitope that is accessible to antibody in plasma membranes and permeabilized cells, but not in intact cells. Such a cytoplasmically oriented domain also is required for the demonstrated role of ponticulin in binding actin to the plasma membrane in vivo and in vitro (Hitt, A. L., J. H. Hartwig, and E. J. Luna. 1994. Ponticulin is the major high affinity link between the plasma membrane and the cortical actin network in Dictyostelium. J. Cell Biol. 126:1433-1444). Thus, ponticulin apparently represents a new category of integral membrane proteins that consists of proteins with both a glycosyl anchor and membrane-spanning peptide domain(s).

Amino Acid Sequence↗

PubMed1995

Morphological fate and sequelae of human atherosclerosis: evaluation of immune mechanisms in atherogenesis through immunohistological and ultrastructural analysis.

Modern techniques of investigation have revealed several similarities between atherosclerosis and chronic inflammation, and that immune mechanisms seem to operate in the incipient and subsequent phases of atherosclerosis. In the present study, the fate and morphogenesis of human atherosclerosis was considered, and the immune aspects of atherogenesis were analysed, using fresh human aorta obtained from autopsy cases. One of the earliest changes in the grossly normal, lesion-prone area of the aorta from young cases (prelesional changes) was the infiltration of blood-borne T lymphocytes and monocytes/macrophages beneath the endothelium. Cell-populated lesions abounding in T lymphocytes and macrophages, often bearing signs of activation, with or without cytoplasmic lipids were found in the fatty streaks, cap and shoulder regions of more advanced atheromatous plaques. The ultrastructural observation of cell-rich areas suggested that cognate cell-to-cell interaction plays a pivotal role in atherosclerosis, as well as cytokine-mediated paracrine or autocrine mechanisms. From an immunological perspective, the areas where both cell types are especially numerous and in close proximity are considered to be the areas with an index of disease activeness or progressiveness. Also, the present authors show evidence of clonal expansion of T lymphocytes. It is most likely that the increase of intimal cells was caused by the recruitment of immunocompetent cells from the blood-stream into the intima and by the clonal expansion of T lymphocytes. In addition, dead or dying cells were identified in areas of different stages ranging from prelesional areas to atheromatous plaques. Thus, the initiation and progression of human atherosclerosis appears to be punctuated by brief episodes of immunological events related to cell infiltration, proliferation and death.

Adolescent↗

PubMed2005

Heregulin-triggered Her-2/neu signaling enhances nuclear accumulation of p21WAF1/CIP1 and protects breast cancer cells from cisplatin-induced genotoxic damage.

Elevated levels of p21WAF1/CIP1, an important mediator of DNA repair, have been observed in various aggressive tumors as well as linked to chemoresistance. We examined whether heregulin (HRG), a member of the EGF-like growth factor family closely related to breast cancer tumorigenesis and metastasis, modulates p21WAF1/CIP1 expression and cellular localization. We used a model system that consisted of MCF-7 cells and MCF-7 cells engineered to overexpress the full-length cDNA of the human HRG gene (MCF-7/HRG). MCF-7/HRG cells demonstrate constitutive hyperactivation of Her-2/neu receptor as well as activation of down-stream PI-3'K/AKT and MAPK signaling cascades. Immunoblotting analyses showed that MCF-7/HRG cells significantly up-regulate p21WAF1/CIP1 expression relative to control MCF-7/pBABE cells, while a strong nuclear accumulation of p21WAF1/CIP1 in MCF-7/HRG cells was revealed by immunofluorescence microscopy studies. Protein degradation analyses demonstrated that the half-life of p21WAF1/CIP1 protein was increased from approximately 35 min in control MCF-7/pBABE cells to >/=3 h in MCF-7/HRG cells. Pharmacological inactivation of the PI-3'K/AKT and MAPK completely prevented HRG-induced accumulation of p21WAF1/CIP1. A structural deletion mutant of HRG (HRG-M4) lacking the N-terminus sequence and the cytoplasmic-transmembrane region of HRG was generated to investigate whether secretion of HRG and transactivation of Her-2/neu actively contributed to HRG-regulated p21WAF1/CIP1 expression and cellular localization. MCF-7 cells engineered to overexpress HRG-M4 did not demonstrate either activation of Her-2/neu, PI-3'K/AKT, or MAPK. Remarkably, HRG-M4 overexpression completely abolished the ability of HRG to promote nuclear accumulation of p21WAF1/CIP1 and concomitantly enhanced the apoptotic effects of cisplatin towards breast cancer cells. This novel interplay between HRG and p21WAF1/CIP1 strongly suggests that one mechanism of HRG-regulated breast cancer cell proliferation, survival, and/or sensitivity to genotoxic damage is to stabilize and promote a nuclear accumulation of p21WAF1/CIP1.

Antineoplastic Agents↗

PubMed1984

Unidirectional transport mechanism of horseradish peroxidase in the vessels of the iris.

When horseradish peroxidase (HRP) is introduced into the blood stream it is retained in the lumen of the iridial vessels. In this paper, we report that when the same tracer is perfused into the anterior chamber of macaque monkeys, it permeates the stroma of the iris and penetrates the lumen of iridial vessels by transcellular vesicular transport. This unidirectional movement of HRP out of the eye is not inhibited by ouabain or fluoroacetate.

Animals↗

PubMed1980

A light and electron microscopic study of the inferior olivary nucleus of the squirrel monkey, Saimiri sciureus.

This study provides a description of the normal morphology of the inferior olive of the squirrel monkey, Saimiri sciureus, at the light and electron imcroscopic level. The cytoarchitecture of the inferior olive was maped from serial transverse sections stained with cresyl violet. In common with other mammals, the inferior olive of the squirrel monkey consists of three subdivisions. The medial accessory olive includes seven subnuclei. Both the dorsal and medial accessory olives extend through approximately 90% of the total length of the inferior olivary complex. The principal olive, consisting of a dorsal and ventral lamella continuous with one another laterally, extends through the rostral 55% of the inferior olive. It is somewhat less convoluted than the principal olive of the macaque (Bowman and Sladek, '73). In most other respects, the inferior olive of the two primates is quite similar. Two patterns of dendritic arborization are noted in Golgi preparations from the caudal principal and accessory olives. Dendrites streaming away from the soma, and dendrites curling around the soma in a "ball-like" pattern were observed in all three subdivisions of the inferior olive caudally. Simple spines are occasionally seen on the soma, and a few simple or club-shaped spines were noted on the proximal portion of the dendritic arborization. Spines are more numerous on distal portions of the dendritic tree, however, and include simple, filiform, club-shaped and occasionally complex, or racemous, spiny appendages. Viewed in the electron microscope, most inferior olivary neurons are seen to contain the typical organelles with the usual conformation and distribution. Rarely, a neuron with an indented nucleus and a thin rim of cytoplasm containing a paucity of organelles and a wispy endoplasmic reticulum is encountered. Axon terminals containing either clear round or clear pleomorphic vesicles are seen in all three olivary subdivisions. In a random survey of 706 axon terminals, 54% contained predominantly clear round vesicles. Large dense cored vesicles are seen in varying numbers in both types of terminals. Rarely, profiles containing mainly large dense cored vesicles are ob served. Axosomatic synapses involving both types of clear vesicle containing terminals are occasionally encountered. Such synapses are symmetrical, regardless of the type of vesicle found in the axon terminal. Axodendritic synapses involving round vesicle containing terminals are assymetrical, while those involving pleomorphic vesicle containing terminals are usually, but not invariably, symmetrical. Axondendritic synapses occur at all levels of the dendritic tree. Very rarely, synapses between an axon terminal and a profile resembling a dendrite, but containing pleomorphic vesicles, has been observed. Synaptic clusters, consisting of a central core of small dendritic elements surrounded by both round and pleomorphic vesicle containing terminals, are found in all three subdivisions of the inferior olive...

Animals↗

PubMed2002

Altered distribution of cell cycle transcriptional regulators during Alzheimer disease.

A number of mechanisms have been proposed to contribute to the selective neuronal cell loss observed during Alzheimer disease (AD). These include the formation and accumulation of amyloid-beta (Abeta)-containing plaques, neurofibrillary tangles (NFTs), and inflammatory processes mediated by astrocytes and microglia. Neuronal responses to such insults in AD brain include increased protein levels and immunoreactivity for kinases known to regulate cell cycle progression. One down-stream target of these cell cycle regulatory proteins, the Retinoblastoma susceptibility gene product (pRb), has been shown to exhibit altered expression patterns in AD. Furthermore, in vitro studies have implicated pRb and one of the transcription factors it regulates, E2F1, in Abeta-induced cell death. To further explore the role of these proteins in AD, we examined the distribution of the E2F1 transcription factor and the hyperphosphorylated form of pRb (ppRb), which is unable to bind and regulate E2F activity, in the cortex of patients with AD and in non-demented controls. We observed increased ppRb and E2FI immunoreactivity in AD brain, with ppRb predominately located in the nucleus and E2F1 in the cytoplasm. Although neither of these proteins significantly co-localized with NFTs, both ppRb and E2F1 were found in cells surrounding a subset of Abeta-containing plaques. These results support a role for G1 to S phase cell cycle regulators in AD.

Aged↗

PubMed1990

A teratological assessment of coal liquefaction products in the rat.

Teratogenicity of coal liquefaction products (CLP) was assessed in the pregnant rat. Three product streams of CLP (medium, hydrotreated medium and heavy fractions) were each administered dermally on Sprague-Dawley rats at doses of 125, 250 or 500 mg kg-1 day-1 from Day 6 through to Day 15 of gestation. Depressed maternal weight gain and reduced number of fetuses resulting from an increased resorption rate, decreased fetal weight and retarded ossification were observed in the group treated with the heavy fraction at a dose of 500 mg kg-1 day-1. The heavy fraction at 500 mg kg-1 day-1 also caused anaemia and increased liver and spleen weights in dams. The dams exposed to the highest dose of three CLP fractions had mild and adaptative hepatic changes consisting of increased cytoplasmic eosinophilia and nuclear anisokaryosis. No treatment-related histological changes were observed in fetuses. None of the fractions demonstrated any teratological effects.

Abnormalities, Drug-Induced↗

PubMed1991

Early stages of trophoblastic invasion of the maternal vascular system during implantation in the macaque and baboon.

Trophoblastic invasion and remodeling of the uteroplacental (spiral) arteries in primates are well-documented, but virally nothing is known of the early stages of these phenomena. Therefore, we examined invasion of the maternal vasculature in macaques and baboons at, and immediately following, implantation. Following penetration of the uterine epithelium (day 9), trophoblast spreads along the residual epithelial basal lamina. By day 10, cytoplasmic processes penetrate the epithelial and endothelial basal laminae, and syncytial trophoblast insinuates itself between maternal endothelial cells. As lacunae develop, both syncytial and cytotrophoblast are exposed to maternal blood. Endovascular cytotrophoblast was first observed in subepithelial dilated capillaries and venules. These vessels are lined by increasingly hypertrophied endothelial cells. The spiral arterioles are unmodified at this time. Particularly interesting was the observation that there is rapid extensive endovascular trophoblast invasion of the spiral arterioles immediately beneath the implantation site. By day 14-16 nearly all of the small arterioles directly beneath the site are completely occluded. There is no invasion of the veins in this region. Somewhat later, the deeper arterioles in the principal zone are invaded. Rather than a continuous stream of cells invading the deeper arterioles, these endovascular cells occur in clusters ranging from a few cells to groups of cells that completely plug the lumen. Our results indicate that trophoblastic invasion of maternal vessels occurs very early; and, at least initially, trophoblast can migrate between and along endothelial cells without causing their lysis. The endovascular cells eventually interrupt the endothelial lining of the arterioles and penetrate the walls of the vessels. The occlusion of arterioles underneath the site suggests that circulation through the lacunae at this stage is indirect. Corresponding stages of human development were examined, and no invasion of arterioles could be observed prior to formation of an extensive cytotrophoblastic shell.

Animals↗

PubMed1996

Novel redistribution of the Ca(2+)-dependent cell adhesion molecule DdCAD-1 during development of Dictyostelium discoideum.

Dictyostelium discoideum cells express DdCAD-1, a Ca(2+)-dependent cell-cell adhesion molecule, soon after the initiation of development. DdCAD-1 is a soluble protein which shares a significant degree of sequence similarity with E-cadherin. Laser scanning confocal microscopy of the subcellular localization of DdCAD-1 has revealed a nonrandom pattern of DdCAD-1 distribution. DdCAD-1 is present mostly as diffusely stained material in the cytoplasm during the initial stage of development. However, a drastic redistribution takes place before the onset of cell aggregation, when DdCAD-1 become localized predominantly at the cell periphery and an enrichment of DdCAD-1 occurs on membrane ruffles. A high concentration of DdCAD-1 also becomes associated with lamellipodia and filopodia, which often appear to participate in cell contact formation. Although DdCAD-1 is present in high concentrations in contact regions during early development, it disappears rapidly from these areas during cell aggregation. This redistribution is accompanied by an accumulation of the Ca(2+)-independent cell adhesion molecule gp80 in contact regions. During chemotactic migration, DdCAD-1 is present primarily on cells at the tip and on the outer margin of cell streams. In contrast, gp80 is concentrated in contact regions among cells within well-developed streams. This dynamic redistribution suggests a unique role for DdCAD-1 in the recruitment of cells into streams and in the formation of initial contacts, but it may not be required to maintain stable contacts in the presence of gp80.

Animals↗

PubMed1992

Structural organization of the follicle-stimulating hormone receptor gene.

We have characterized a series of rat genomic clones that code for the FSH receptor (FSHR) gene and approximately 14.8 kilobases of DNA up-stream of the transcriptional start sites. Southern blot analysis indicated that there was only a single gene for the FSHR. Primer extension and S1 nuclease experiments revealed the presence of two major transcriptional start sites at positions -80 and -98 relative to the translational start site. Transient expression studies of a fusion gene containing 830 basepairs of DNA 5' to the translational start site linked to the reporter gene chloramphenicol acyltransferase have shown that this portion of the gene is capable of acting as a transcriptional promoter in rat Sertoli cells. The FSHR gene contained 10 exons and nine introns. The first nine exons encoded the extensive amino-terminal domain of the receptor, while the last exon encoded the transmembrane-spanning and cytoplasmic domains. A repeated motif similar to that observed in the leucine-rich glycoprotein family was delineated within exons 2-9. Comparison of the FSHR gene to the LH receptor gene revealed a number of striking similarities which clearly indicate that these receptors evolved through gene duplication. The ancestral gene for these receptors presumably arose from a series of tandem duplications of the leucine-rich motif, which when combined with the common ancestral gene of the G-protein-coupled receptor family led to the current gene structure of the glycoprotein hormone receptors.

Amino Acid Sequence↗

PubMed1995

Immunohistochemical proof of intraneural localization of herpes simplex virus in experimental retinitis.

A unilateral intravitreal inoculation of herpes simplex virus type 1 (HSV-1) induced bilateral retinitis and encephalitis in the rat. Immunohistochemistry was employed to clarify the pathway of transmission of HSV-1 from the inoculated eye to the contralateral eye, and to identify localization of the viral antigen in the retina, optic nerve and brain. At an early stage of the post-inoculation period, HSV-1 immunoreactivity was first seen in the cytoplasm of Müller cells and then in various cells of the inner nuclear layer in the inoculated eye. At a later stage, HSV-1 immunoreactivity was seen in some retinal ganglion cells and optic nerve fibers in the inoculated eye. In the brain, HSV-1 was found in the optic chiasm, bilateral primary visual centers (bilateral suprachiasmatic nuclei, bilateral lateral geniculate nuclei, bilateral superior colliculus and bilateral pretectum) and bilateral visual cortex. HSV-1 was also demonstrated in the retinal ganglion cells, neural cells in the inner nuclear layer, and Müller cells in the contralateral eye. We found that HSV-1 antigen in the retina of the contralateral eye was transmitted through the optic nerve, visual pathway and nuclei, but not through the blood stream.

Animals↗

PubMed1988

A comparison of endocrine pancreatic tissue in adults of four species of lampreys in British Columbia: a morphological and immunohistochemical study.

Histological techniques and immunohistochemistry with antisera against insulin and somatostatin were used in a study of the identification and the distribution of endocrine pancreatic tissue in adults of four species of lampreys in British Columbia. The fine structure of the pancreatic cells of one of the species was also examined. The four species (Lampetra ayresi, Lampetra tridentata, Lampetra macrostoma, and Lampetra richardsoni) all possess cranial and caudal pancreatic masses and an intervening intermediate cord, but there are variations in amount and deposition of the pancreatic tissue with respect to the alimentary canal and the liver which appear to be species specific. There is also some variation in the distribution of pancreatic tissue between L. richardsoni of different stream populations. A newly identified parasitic variety of L. richardsoni in Morrison Creek, called L. richardsoni var. marifuga, usually has no cranial pancreas but has an extensive intermediate cord. The distribution of pancreatic tissue in these lampreys is of relevance to taxonomy and to variations in development of the endocrine pancreas during lamprey metamorphosis. The pancreatic tissue of all species and var. marifuga is composed of cells which are immunoreactive to either insulin or somatostatin antisera. The fine structure of cells from the cranial and caudal pancreatic tissue from L. ayresi does not vary with saltwater and freshwater acclimation. Insulin-containing B cells and somatostatin-containing D cells are present in equal numbers in both pancreatic regions and the cells each have characteristic cytoplasmic granules. A third cell type is most abundant in the cranial pancreas but it is of unknown function.

Animals↗

PubMed1979

Induction of a plasmodial stage of Physarum without plasmalemma invaginations.

Experimentally generated protoplasmic drops of Physarum show time-dependent differentiation processes, i.e. regeneration of plasmalemma, actomyosin fibrillogenesis and regeneration of the plasmalemma invagination system. According to Hatano (1970), caffeine treatment of drops results in a pinching off process of small translucent droplets in which specific effects of Ca++ on protoplasmic streaming phenomena were demonstrated. The light and electron microscopic investigation of the original drop reveal that the time-dependent differentiation processes, e.g. actomyosin fibrillogenesis, are not inhibited by caffeine. However, caffeine hinders the regeneration of the plasmalemma invaginations in the original drop (up to a drop age of 30--40 min). The experimental advantage of this stage of Physarum with full vitality, but without plasmalemma invaginations is discussed.

Caffeine↗

PubMed2003

Effect of acute ozone exposure on locomotor behavior and striatal function.

Ozone exposure, depending on the dose, is a noninvasive model of oxidative stress. The purpose of this work was to study striatal damage and cell death induced by oxidative stress. Sixty-three male Wistar rats were divided into two groups--Group 1: animals were exposed to an air stream free of ozone for 4 h; and Group 2: animals were exposed to 1 ppm of ozone for 4 h. Four subgroups in each treatment group were then tested 3 h after control or ozone exposure for: (1) exploratory and freezing behavior; (2) lipid peroxidation levels; (3) in vivo release of amino acid and monoamine transmitters, and metabolites and nitric oxide; and (4) striatal ultrastructural changes. Results showed that the ozone decreased exploratory and increased freezing behaviors. It also increased striatal lipoperoxidation levels and basal dopamine, glutamate, and nitric oxide (arginine, citrulline, and nitrate used as indices) concentrations and decreased those of 5-HT. Concentrations of GABA were initially decreased 3 h after ozone but then were increased 3 and 5 days afterwards. Increased lipofucsine, neuronal cytoplasm and dendrite vacuolation, and dilation of rough endoplasmic reticulum cisterns and dark cells were observed in striatal medium spiny neurons in ozone-exposed rats. These alterations suggest a neurodegenerative process caused by oxidative stress after acute ozone exposure.

Amino Acids↗