Science.gov

Sample records for adult rat cerebellum

  1. Lack of neurogenesis in the adult rat cerebellum after Purkinje cell degeneration and growth factor infusion.

    PubMed

    Grimaldi, Piercesare; Rossi, Ferdinando

    2006-05-01

    Although constitutive neurogenesis exclusively occurs in restricted regions of the adult mammalian brain, resident progenitors can be isolated from many different CNS sites, and neuronal neogeneration can be stimulated in vivo by injury or infusion of growth factors. To ask whether latent compensatory mechanisms, which may be exploited to promote repair processes, are present throughout the CNS, we examined the neurogenic potentialities of the adult rat cerebellum in normal conditions, following injury, and after infusion of growth factors. Degeneration of Purkinje cells was induced by intracerebroventricular administration of the toxin saporin, conjugated to anti-p75 antibodies. In addition, epidermal growth factor and basic fibroblast growth factor, or FGF8, were infused for 2 weeks to either intact or injured animals. In all conditions, proliferating cells were identified from bromodeoxyuridine (BrdU) incorporation. In the unmanipulated cerebellum there were rare dividing cells, mainly represented by NG2-positive presumptive oligodendrocyte precursors. Mitotic activity was strongly enhanced in cortical areas with Purkinje cell degeneration, being mostly sustained by microglia, plus minor fractions of NG2-expressing cells, astrocytes and oligodendrocytes. In contrast, growth factor infusion had a weak effect on both intact and injured cerebella. In all experimental conditions, we never found any BrdU-positive cells coexpressing distinctive markers for immature or differentiated cerebellar neurons. Therefore, although some progenitor cells reside in the adult cerebellum, the local environment, either intact or injured, does not provide efficient cues to direct their differentiation towards neuronal phenotypes. In addition, neurogenic potentialities cannot be induced or boosted by the application of growth factors which are effective in other CNS regions.

  2. Penconazole alters redox status, cholinergic function, and membrane-bound ATPases in the cerebrum and cerebellum of adult rats.

    PubMed

    Chaâbane, M; Ghorbel, I; Elwej, A; Mnif, H; Boudawara, T; Chaâbouni, S Ellouze; Zeghal, N; Soudani, N

    2016-10-12

    Pesticides exposure causes usually harmful effects to the environment and human health. The present study aimed to investigate the potential toxic effects of penconazole, a triazole fungicide, on the cerebrum and cerebellum of adult rats. Penconazole was administered intraperitoneally to male Wistar rats at a dose of 67 mg kg(-1) body weight every 2 days during 9 days. Results showed that penconazole induced oxidative stress in rat cerebrum and cerebellum tissues. In fact, we have found a significant increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, as well as an alteration of the antioxidant status, enzymatic (superoxide dismutase and catalase) and nonenzymatic (glutathione), the cholinergic function, and membrane-bound ATPases (Na(+)/K(+)-ATPase and Mg(2+)-ATPase). Penconazole also provoked histological alterations marked by pyknotic and vacuolated neurons in the cerebrum and apoptosis and edema in the cerebellum Purkinje cells' layer. Therefore, the use of this neurotoxicant fungicide must be regularly monitored in the environment.

  3. Aluminium and Acrylamide Disrupt Cerebellum Redox States, Cholinergic Function and Membrane-Bound ATPase in Adult Rats and Their Offspring.

    PubMed

    Ghorbel, Imen; Amara, Ibtissem Ben; Ktari, Naourez; Elwej, Awatef; Boudawara, Ons; Boudawara, Tahia; Zeghal, Najiba

    2016-12-01

    Accumulation of aluminium and acrylamide in food is a major source of human exposure. Their adverse effects are well documented, but there is no information about the health problems arising from their combined exposure. The aim of the present study was to examine the possible neurotoxic effects after co-exposure of pregnant and lactating rats to aluminium and acrylamide in order to evaluate redox state, cholinergic function and membrane-bound ATPases in the cerebellum of adult rats and their progeny. Pregnant female rats have received aluminium (50 mg/kg body weight) via drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination from the 14th day of pregnancy until day 14 after delivery. Exposure to these toxicants provoked an increase in malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels and a decrease in SOD, CAT, GPx, Na(+)K(+)-ATPase, Mg(2+)-ATPase and AChE activities in the cerebellum of mothers and their suckling pups. A reduction in GSH, NPSH and vitamin C levels was also observed. These changes were confirmed by histological results. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in the cerebellum of mothers and their progeny.

  4. Purkinje cell number decreases in the adult female rat cerebellum following exposure to 900 MHz electromagnetic field.

    PubMed

    Sonmez, Osman Fikret; Odaci, Ersan; Bas, Orhan; Kaplan, Süleyman

    2010-10-14

    The biological effects of electromagnetic field (EMF) exposure from mobile phones have growing concern among scientists since there are some reports showing increased risk for human health, especially in the use of mobile phones for a long duration. In the presented study, the effects on the number of Purkinje cells in the cerebellum of 16-week (16 weeks) old female rats were investigated following exposure to 900 MHz EMF. Three groups of rats, a control group (CG), sham exposed group (SG) and an electromagnetic field exposed group (EMFG) were used in this study. While EMFG group rats were exposed to 900 MHz EMF (1h/day for 28 days) in an exposure tube, SG was placed in the exposure tube but not exposed to EMF (1h/day for 28 days). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head). The CG was not placed into the exposure tube nor was it exposed to EMF during the study period. At the end of the experiment, all of the female rats were sacrificed and the number of Purkinje cells was estimated using a stereological counting technique. Histopathological evaluations were also done on sections of the cerebellum. Results showed that the total number of Purkinje cells in the cerebellum of the EMFG was significantly lower than those of CG (p<0.004) and SG (p<0.002). In addition, there was no significant difference at the 0.05 level between the rats' body and brain weights in the EMFG and CG or SG. Therefore, it is suggested that long duration exposure to 900 MHz EMF leads to decreases of Purkinje cell numbers in the female rat cerebellum.

  5. Low nanomolar serotonin inhibits the glutamate receptor/nitric oxide/cyclic GMP pathway in slices from adult rat cerebellum.

    PubMed

    Maura, G; Guadagnin, A; Raiteri, M

    1995-09-01

    The function of serotonin afferents to the cerebellum has been investigated by monitoring the effects of serotoninergic drugs on the production of cyclic GMP elicited in cerebellar slices by activation of ionotropic glutamate receptors. Exposure of adult rat cerebellar slices to N-methyl-D-aspartate (1 nM to 1 microM) or to (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA; 1 nM to 10 microM) elicited concentration-dependent and saturable rises in the levels of cyclic GMP. These responses were blocked by selective antagonists at the N-methyl-D-aspartate or AMPA receptors and by inhibiting nitric oxide synthase, but were insensitive to tetrodotoxin. When tested between 0.1 and 10 nM, serotonin, the serotonin1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin and the serotonin2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane inhibited, concentration-dependently, the cyclic GMP responses evoked by near-maximal (0.1 microM) concentrations of N-methyl-D-aspartate or AMPA. The EC50 values (concentrations causing half-maximal effect) ranged between 0.7 and 2.1 nM. The actions of serotonin were totally abolished by methiothepin, a mixed-type serotonin receptor antagonist. Thus, the serotonergic cerebellar afferents may exert a potent inhibitory control on the excitatory transmission mediated by N-methyl-D-aspartate and AMPA receptors; the inhibition occurs through both serotonin1A and serotonin2 receptors. As the glutamate receptor-dependent cyclic GMP responses involve production of nitric oxide, a diffusible activator of guanylate cyclase, the above inhibitory serotonin receptors may have multiple localization.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. THE FINE STRUCTURE OF THE RAT CEREBELLUM

    PubMed Central

    Herndon, Robert M.

    1964-01-01

    This paper describes the fine structure of the granule cells, stellate neurons, astrocytes, Bergmann glia, oligodendrocytes, and microglia of the rat cerebellum after fixation by perfusion with buffered 1 per cent osmium tetroxide. Criteria are given for differentiating the various cell types, and the findings are correlated with previous light microscope and electron microscope studies of the cerebellum. PMID:14222815

  7. Trace element distribution in the rat cerebellum

    SciTech Connect

    Kwiatek, W.M.; Long, G.J.; Pounds, J.G.; Reuhl, K.R.; Hanson, A.L.; Jones, K.W.

    1989-10-01

    Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with x-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and non-destructive irradiation. Trace elements were measured in thin rat brain sections of 20-micrometers thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppM wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semi-quantitative mapping of the TE distribution in a section were used.

  8. Anomalous extracellular diffusion in rat cerebellum.

    PubMed

    Xiao, Fanrong; Hrabe, Jan; Hrabetova, Sabina

    2015-05-05

    Extracellular space (ECS) is a major channel transporting biologically active molecules and drugs in the brain. Diffusion-mediated transport of these substances is hindered by the ECS structure but the microscopic basis of this hindrance is not fully understood. One hypothesis proposes that the hindrance originates in large part from the presence of dead-space (DS) microdomains that can transiently retain diffusing molecules. Because previous theoretical and modeling work reported an initial period of anomalous diffusion in similar environments, we expected that brain regions densely populated by DS microdomains would exhibit anomalous extracellular diffusion. Specifically, we targeted granular layers (GL) of rat and turtle cerebella that are populated with large and geometrically complex glomeruli. The integrative optical imaging (IOI) method was employed to evaluate diffusion of fluorophore-labeled dextran (MW 3000) in GL, and the IOI data analysis was adapted to quantify the anomalous diffusion exponent dw from the IOI records. Diffusion was significantly anomalous in rat GL, where dw reached 4.8. In the geometrically simpler turtle GL, dw was elevated but not robustly anomalous (dw = 2.6). The experimental work was complemented by numerical Monte Carlo simulations of anomalous ECS diffusion in several three-dimensional tissue models containing glomeruli-like structures. It demonstrated that both the duration of transiently anomalous diffusion and the anomalous exponent depend on the size of model glomeruli and the degree of their wrapping. In conclusion, we have found anomalous extracellular diffusion in the GL of rat cerebellum. This finding lends support to the DS microdomain hypothesis. Transiently anomalous diffusion also has a profound effect on the spatiotemporal distribution of molecules released into the ECS, especially at diffusion distances on the order of a few cell diameters, speeding up short-range diffusion-mediated signals in less permeable

  9. Anomalous Extracellular Diffusion in Rat Cerebellum

    PubMed Central

    Xiao, Fanrong; Hrabe, Jan; Hrabetova, Sabina

    2015-01-01

    Extracellular space (ECS) is a major channel transporting biologically active molecules and drugs in the brain. Diffusion-mediated transport of these substances is hindered by the ECS structure but the microscopic basis of this hindrance is not fully understood. One hypothesis proposes that the hindrance originates in large part from the presence of dead-space (DS) microdomains that can transiently retain diffusing molecules. Because previous theoretical and modeling work reported an initial period of anomalous diffusion in similar environments, we expected that brain regions densely populated by DS microdomains would exhibit anomalous extracellular diffusion. Specifically, we targeted granular layers (GL) of rat and turtle cerebella that are populated with large and geometrically complex glomeruli. The integrative optical imaging (IOI) method was employed to evaluate diffusion of fluorophore-labeled dextran (MW 3000) in GL, and the IOI data analysis was adapted to quantify the anomalous diffusion exponent dw from the IOI records. Diffusion was significantly anomalous in rat GL, where dw reached 4.8. In the geometrically simpler turtle GL, dw was elevated but not robustly anomalous (dw = 2.6). The experimental work was complemented by numerical Monte Carlo simulations of anomalous ECS diffusion in several three-dimensional tissue models containing glomeruli-like structures. It demonstrated that both the duration of transiently anomalous diffusion and the anomalous exponent depend on the size of model glomeruli and the degree of their wrapping. In conclusion, we have found anomalous extracellular diffusion in the GL of rat cerebellum. This finding lends support to the DS microdomain hypothesis. Transiently anomalous diffusion also has a profound effect on the spatiotemporal distribution of molecules released into the ECS, especially at diffusion distances on the order of a few cell diameters, speeding up short-range diffusion-mediated signals in less permeable

  10. Adult neurogenesis without germinal layers: the "atypical" cerebellum of rabbits.

    PubMed

    Ponti, G; Crociara, P; Armentano, M; Bonfanti, L

    2010-06-01

    Unlike non mammalian vertebrates, adult neurogenesis in mammals is detectable in highly restricted brain sites. Persistent neurogenesis is thought to depend on stem cells residing in neural stem cell niches which are remnants of the embryonic germinal layers. Local progenitors which retain some proliferative capacity have been identified in the mature brain parenchyma, yet they do not support a constitutive, 'actual' neurogenesis, but rather a 'potential' neurogenesis which does not extrinsecate fully and spontaneously in vivo. In contrast with such a view, genesis of neuronal and glial cells from local progenitors does occur in the peripuberal and adult rabbit cerebellum. This process is independent from persisting germinal layers and involves different cell populations.

  11. Alternative kynurenic acid synthesis routes studied in the rat cerebellum

    PubMed Central

    Blanco Ayala, Tonali; Lugo Huitrón, Rafael; Carmona Aparicio, Liliana; Ramírez Ortega, Daniela; González Esquivel, Dinora; Pedraza Chaverrí, José; Pérez de la Cruz, Gonzalo; Ríos, Camilo; Schwarcz, Robert; Pérez de la Cruz, Verónica

    2015-01-01

    Kynurenic acid (KYNA), an astrocyte-derived, endogenous antagonist of α7 nicotinic acetylcholine and excitatory amino acid receptors, regulates glutamatergic, GABAergic, cholinergic and dopaminergic neurotransmission in several regions of the rodent brain. Synthesis of KYNA in the brain and elsewhere is generally attributed to the enzymatic conversion of L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). However, alternative routes, including KYNA formation from D-kynurenine (D-KYN) by D-amino acid oxidase (DAAO) and the direct transformation of kynurenine to KYNA by reactive oxygen species (ROS), have been demonstrated in the rat brain. Using the rat cerebellum, a region of low KAT activity and high DAAO activity, the present experiments were designed to examine KYNA production from L-KYN or D-KYN by KAT and DAAO, respectively, and to investigate the effect of ROS on KYNA synthesis. In chemical combinatorial systems, both L-KYN and D-KYN interacted directly with peroxynitrite (ONOO−) and hydroxyl radicals (OH•), resulting in the formation of KYNA. In tissue homogenates, the non-specific KAT inhibitor aminooxyacetic acid (AOAA; 1 mM) reduced KYNA production from L-KYN and D-KYN by 85.1 ± 1.7% and 27.1 ± 4.5%, respectively. Addition of DAAO inhibitors (benzoic acid, kojic acid or 3-methylpyrazole-5-carboxylic acid; 5 μM each) attenuated KYNA formation from L-KYN and D-KYN by ~35% and ~66%, respectively. ONOO− (25 μM) potentiated KYNA production from both L-KYN and D-KYN, and these effects were reduced by DAAO inhibition. AOAA attenuated KYNA production from L-KYN + ONOO− but not from D-KYN + ONOO−. In vivo, extracellular KYNA levels increased rapidly after perfusion of ONOO− and, more prominently, after subsequent perfusion with L-KYN or D-KYN (100 μM). Taken together, these results suggest that different mechanisms are involved in KYNA production in the rat cerebellum, and that, specifically, DAAO and ROS can function as alternative

  12. Disynaptic Subthalamic Input to the Posterior Cerebellum in Rat

    PubMed Central

    Jwair, Saad; Coulon, Patrice; Ruigrok, Tom J. H.

    2017-01-01

    In the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. Yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. Here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (STN) and the cerebellar cortex as has been demonstrated earlier for the primate. A mixture of unmodified rabies virus (RABV: CVS 11) and cholera toxin B-subunit (CTb) was injected at places in the posterior cerebellar cortex of nine rats. The survival time was chosen to allow for disynaptic retrograde transneuronal infection of RABV. We examined the STN for neurons infected with RABV in all nine cases and related the results with the location of the RABV/CTb injection site, which ranged from the vermis of lobule VII, to the paravermis and hemispheres of the paramedian lobule and crus 2a. We found that cases with injection sites in the vermis of lobule VII showed prominent RABV labeling in the STN. In contrast, almost no subthalamic labeling was noted in cases with paravermal or hemispheral injection sites. We show circumstantial evidence that not only the pontine nuclei but also the pedunculotegmental nucleus may act as the intermediary in the connection from STN to cerebellar cortex. This finding implies that in the rat the STN links disynaptically to the vermal part of lobule VII of the cerebellar cortex, without any major involvement of the cerebellar areas that are linked to sensorimotor functions. As vermal lobule VII recently has been shown to process disynaptic input from the retrosplenial and orbitofrontal cortices, we hypothesize that in the rat the subthalamic input to cerebellar function might be used to influence more prominently non-motor functions of the cerebellum than motor functions. This

  13. Disynaptic Subthalamic Input to the Posterior Cerebellum in Rat.

    PubMed

    Jwair, Saad; Coulon, Patrice; Ruigrok, Tom J H

    2017-01-01

    In the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. Yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. Here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (STN) and the cerebellar cortex as has been demonstrated earlier for the primate. A mixture of unmodified rabies virus (RABV: CVS 11) and cholera toxin B-subunit (CTb) was injected at places in the posterior cerebellar cortex of nine rats. The survival time was chosen to allow for disynaptic retrograde transneuronal infection of RABV. We examined the STN for neurons infected with RABV in all nine cases and related the results with the location of the RABV/CTb injection site, which ranged from the vermis of lobule VII, to the paravermis and hemispheres of the paramedian lobule and crus 2a. We found that cases with injection sites in the vermis of lobule VII showed prominent RABV labeling in the STN. In contrast, almost no subthalamic labeling was noted in cases with paravermal or hemispheral injection sites. We show circumstantial evidence that not only the pontine nuclei but also the pedunculotegmental nucleus may act as the intermediary in the connection from STN to cerebellar cortex. This finding implies that in the rat the STN links disynaptically to the vermal part of lobule VII of the cerebellar cortex, without any major involvement of the cerebellar areas that are linked to sensorimotor functions. As vermal lobule VII recently has been shown to process disynaptic input from the retrosplenial and orbitofrontal cortices, we hypothesize that in the rat the subthalamic input to cerebellar function might be used to influence more prominently non-motor functions of the cerebellum than motor functions. This

  14. Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla.

    PubMed

    Sathyasaikumar, K V; Swapna, I; Reddy, P V B; Murthy, Ch R K; Dutta Gupta, A; Senthilkumaran, B; Reddanna, P

    2007-03-01

    Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.

  15. Maturational Patterns of Iodothyronine Phenolic and Tyrosyl Ring Deiodinase Activities in Rat Cerebrum, Cerebellum, and Hypothalamus

    PubMed Central

    Kaplan, Michael M.; Yaskoski, Kimberlee A.

    1981-01-01

    To explore the control of thyroid hormone metabolism in brain during maturation, we have measured iodothyronine deiodination in homogenates of rat cerebrum, cerebellum, and hypothalamus from 1 d postnatally through adulthood. Homogenates were incubated with 125I-l-thyroxine (T4) + [131I]3,5,3′-l-triiodothyronine (T3) + 100 mM dithiothreitol. Nonradioactive T4, T3, and 3,3′,5′-triiodothyronine (rT3) were included, as appropriate. The net production rate of [125I]T3 from T4 in 1-d cerebral homogenates was similar to the rate in adult cerebral homogenates (9.9±2.5[SEM]% vs. 8.9±1.2% T4 to T3 conversion in 2 h). Production of T3 was not detectable in 1-d cerebellar and hypothalamic homogenates. The net T3 production rate in adult cerebellar homogenates was twice as great as, and that in adult hypothalamic homogenates similar to, the rate in cerebral homogenates. Tyrosyl ring deiodination rates of T4 and T3 were more than three times as great in cerebral homogenates from 1-d-old rats as in adult cerebral homogenates. In cerebellar homogenates from 1-d-old rats, tyrosyl ring deiodination rates were much greater than the rates in adult cerebellar homogenates, but less than those in 1-d cerebral homogenates. In 1-d hypothalamic homogenates, tyrosyl ring deiodination rates were the highest of all the tissues tested, whereas rates in adult hypothalamic homogenates were similar to those in adult cerebral homogenates. During maturation, T4 5′-deiodination rates increased after 7 d and exceeded adult rates between 14 and 35 d in cerebral and cerebellar homogenates, and at 28 and 35 d in hypothalamic homogenates. In cerebral homogenates, the peak in reaction rate at 28 d reflected an increase in the maximum enzyme activity (Vmax) of the reaction. T4 and T3 tyrosyl ring deiodination rates decreased progressively with age down to adult rates, which were attained at 14 d for cerebrum and cerebellum and at 28 d for hypothalamus. These studies demonstrate quantitative

  16. GABAB receptor stimulation by baclofen and taurine enhances excitatory amino acid induced phosphatidylinositol turnover in neonatal rat cerebellum.

    PubMed

    Smith, S S; Li, J

    1991-10-28

    Excitatory amino acid stimulation of phosphatidylinositol (PI) hydrolysis has been associated with development of the CNS. Normally minimally ineffective in stimulating PI hydrolysis in the neonatal rat cerebellum, N-methyl-D-aspartate (NMDA) increased levels of PI hydrolysis 82.3 +/- 5.5% above basal values in the presence of 1 microM baclofen, a gamma-aminobutyric acidB (GABAB) receptor agonist. This effect was observed at day 7 but not in adult cerebellum. The effect of baclofen could be mimicked by low dose GABA and taurine, actions which were blocked by prior application of a specific GABAB antagonist. Therefore, the ability of NMDA to stimulate PI hydrolysis in neonatal cerebellar tissue may be regulated by the degree of GABAB receptor stimulation.

  17. Increased activity of tyrosine hydroxylase in the cerebellum of the x-irradiated dystonic rat

    SciTech Connect

    Dopico, A.M.; Rios, H.; Mayo, J.; Zieher, L.M. )

    1990-08-01

    The exposure of the cephalic end of rats to repeated doses of x-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 {plus minus} 4 ng/CE and 2.8 {plus minus} 1.5 ng/CE, respectively) and x-irradiated rats (17.1 {plus minus} 1 ng/CE and 8.3 {plus minus} 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally x-irradiated animals when compared to age-matched controls (16.4 {plus minus} 1.4 vs 6.32 {plus minus} 0.6 nmol CO2/h/mg prot., p less than 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 {plus minus} 23.8 vs 408.2 {plus minus} 21.5 nmol CO2/h/CE, p less than 0.01 (controls and x-treated, respectively). These results suggest that x-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.

  18. D-Galactose Causes Motor Coordination Impairment, and Histological and Biochemical Changes in the Cerebellum of Rats.

    PubMed

    Rodrigues, André Felipe; Biasibetti, Helena; Zanotto, Bruna Stela; Sanches, Eduardo Farias; Schmitz, Felipe; Nunes, Vinícius Tejada; Pierozan, Paula; Manfredini, Vanusa; Magro, Débora Delwing Dal; Netto, Carlos Alexandre; Wyse, Angela T S

    2016-06-20

    Classical galactosemia is an inborn error of carbohydrate metabolism in which patients accumulate high concentration of galactose in the brain. The most common treatment is a galactose-restricted diet. However, even treated patients develop several complications. One of the most common symptoms is motor coordination impairment, including affected gait, balance, and speech, as well as tremor and ataxia. In the present study, we investigated the effects of intracerebroventricular galactose administration on motor coordination, as well as on histological and biochemical parameters in cerebellum of adult rats. Wistar rats received 5 μL of galactose (4 mM) or saline by intracerebroventricular injection. The animals performed the beam walking test at 1 and 24 h after galactose administration. Histological and biochemical parameters were performed 24 h after the injections. The results showed motor coordination impairment at 24 h after galactose injection. Galactose also decreased the number of cells in the molecular and granular layers of the cerebellum. The immunohistochemistry results suggest that the cell types lost by galactose are neurons and astrocytes in the spinocerebellum and neurons in the cerebrocerebellum. Galactose increased active caspase-3 immunocontent and acetylcholinesterase activity, decreased acetylcholinesterase immunocontent, glutathione, and BDNF levels, as well as caused protein and DNA damage. Our results suggest that galactose induces histological and biochemical changes in cerebellum, which can be associated with motor coordination impairment.

  19. Analysis of β-N-methylamino-L-alanine (L-BMAA) neurotoxicity in rat cerebellum.

    PubMed

    Muñoz-Sáez, Emma; de Munck García, Estefanía; Arahuetes Portero, Rosa Ma; Martínez, Ana; Solas Alados, Ma Teresa; Miguel, Begoña Gómez

    2015-05-01

    Due to its structural similarity to glutamate, L-BMAA could be a trigger for neurodegenerative disorders caused by changes in the intracellular medium, such as increased oxidative stress, mitochondrial dysfunction, impaired synthesis and protein degradation and the imbalance of some enzymes. It is also important to note that according to some published studies, L-BMAA will be incorporated into proteins, causing the alteration of protein homeostasis. Neuronal cells are particularly prone to suffer damage in protein folding and protein accumulation because they have not performed cellular division. In this work, we will analyse the cerebellum impairment triggered by L-BMAA in treated rats. The cerebellum is one of the most important subcortical motor centres and ensures that movements are performed with spatial and temporal precision. Cerebellum damage caused by L-BMAA can contribute to motor impairment. To characterize this neurodegenerative pathology, we first carried out ultrastructure analysis in Purkinje cells showing altered mitochondria, endoplasmic reticulum (ER), and Golgi apparatus (GA). We then performed biochemical assays of GSK3 and TDP-43 in cerebellum, obtaining an increase of both biomarkers with L-BMAA treatment and, finally, performed autophagy studies that revealed a higher level of these processes after treatment. This work provides evidence of cerebellar damage in rats after treatment with L-BMAA. Three months after treatment, affected rats cannot restore the normal functions of the cerebellum regarding motor coordination and postural control.

  20. Protective effect of Bacopa monniera on methyl mercury-induced oxidative stress in cerebellum of rats.

    PubMed

    Sumathi, Thangarajan; Shobana, Chandrasekar; Christinal, Johnson; Anusha, Chandran

    2012-08-01

    Methyl mercury (MeHg) is a ubiquitous environmental pollutant leading to neurological and developmental deficits in animals and human beings. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. The objective of the present study was to investigate whether Bacopa monniera extract (BME) could potentially inhibit MeHg-induced toxicity in the cerebellum of rat brain. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with BME (40 mg/kg, orally) for 21 days. After the treatment period, we observed that MeHg exposure significantly inhibited the activities of superoxide dismutase, catalase, glutathione peroxidase, and increased the glutathione reductase activity in cerebellum. It was also found that the level of thiobarbituric acid-reactive substances was increased with the concomitant decrease in the glutathione level in MeHg-induced rats. These alterations were prevented by the administration of BME. Behavioral interference in the MeHg-exposed animals was evident through a marked deficit in the motor performance in the rotarod task, which was completely recovered to control the levels by BME administration. The total mercury content in the cerebellum of MeHg-induced rats was also increased which was measured by atomic absorption spectrometry. The levels of NO(2) (-) and NO(3) (-) in the serum were found to be significantly increased in the MeHg-induced rats, whereas treatment with BME significantly decreased their levels in serum to near normal when compared to MeHg-induced rats. These findings strongly implicate that BM has potential to protect brain from oxidative damage resulting from MeHg-induced neurotoxicity in rat.

  1. Increased nitric oxide levels in cerebellum of cachectic rats with Walker 256 solid tumor.

    PubMed

    Fenner, Fabio Leandro; Guarnier, Flavia Alessandra; Bernardes, Sara Santos; Ramalho, Leandra Naira Zambelli; Cecchini, Rubens; Cecchini, Alessandra Lourenço

    2015-01-01

    In cancer cachexia, the role of nitric oxide (NO) in the central nervous system remains unclear. Cerebellar degeneration has been reported in cancer patients, but the participation of NO has not been studied. Thus, this study investigated the mechanism of oxidative cerebellar injury in a time-course cancer cachexia experimental model. The cachexia index is progressive and evident during the evolution of the tumor. Nitric oxide and lipid hydroperoxidation quantification was performed using a very sensitive and precise chemiluminescence method, which showed that both analyzed parameters were increased after tumor implantation. In the day 5 group, NO was significantly increased, and this experimental time was chosen to treat the rats with the NO inhibitors N-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). When treated with NO inhibitors, a significant decrease in both NO and lipid hydroperoxide levels occurred in the cerebellum. 3-nitrotyrosine was also analyzed in cerebellar tissue by immunohistochemistry; it was increased at the three experimental time points studied, and decreased when treated with L-NAME and AG. Besides demonstrating that lipid hydroperoxidation in the cerebellum of rats with cachexia increases in a time-dependent manner, this study is the first to describe the participation of NO and its oxidized product 3-NT in the cerebellum of cachectic rats bearing the Walker 256 solid tumor.

  2. Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat (Heterocephalus glaber).

    PubMed

    Sarko, Diana K; Leitch, Duncan B; Catania, Kenneth C

    2013-01-01

    The naked mole-rat (Heterocephalus glaber) is a small fossorial rodent with specialized dentition that is reflected by the large cortical area dedicated to representation of the prominent incisors. Due to naked mole-rats' behavioral reliance on the incisors for digging and for manipulating objects, as well as their ability to move the lower incisors independently, we hypothesized that expanded somatosensory representations of the incisors would be present within the cerebellum in order to accommodate a greater degree of proprioceptive, cutaneous, and periodontal input. Multiunit electrophysiological recordings targeting the ansiform lobule were used to investigate tactile inputs from receptive fields on the entire body with a focus on the incisors. Similar to other rodents, a fractured somatotopy appeared to be present with discrete representations of the same receptive fields repeated within each folium of the cerebellum. These findings confirm the presence of somatosensory inputs to a large area of the naked mole-rat cerebellum with particularly extensive representations of the lower incisors and mystacial vibrissae. We speculate that these extensive inputs facilitate processing of tactile cues as part of a sensorimotor integration network that optimizes how sensory stimuli are acquired through active exploration and in turn adjusts motor outputs (such as independent movement of the lower incisors). These results highlight the diverse sensory specializations and corresponding brain organizational schemes that have evolved in different mammals to facilitate exploration of and interaction with their environment.

  3. Effect of delta9-tetrahydrocannabinol on phosphorylated CREB in rat cerebellum: an immunohistochemical study.

    PubMed

    Casu, Maria Antonietta; Pisu, Carla; Sanna, Angela; Tambaro, Simone; Spada, Gabriele Pinna; Mongeau, Raymond; Pani, Luca

    2005-06-28

    Several converging lines of evidence indicate that drugs of abuse may exert their long-term effects on the central nervous system by modulating signaling pathways controlling gene expression. Cannabinoids produce, beside locomotor effects, cognitive impairment through central CB1 cannabinoid receptors. Data clearly indicate that the cerebellum, an area enriched with CB1 receptors, has a role not only in motor function but also in cognition. This immunohistochemical study examines the effect of delta9-tetrahydrocannabinol (delta9-THC), the principal psychoactive component of marijuana, on the levels of phosphorylated CREB (p-CREB) in the rat cerebellum. Acute treatments with delta9-THC at doses of 5 or 10 mg/kg induced a significant increase of p-CREB in the granule cell layer of the cerebellum, an effect blocked by the CB1 receptor antagonist SR 141716A. Following chronic delta9-THC administration (10 mg/kg/day for 4 weeks), the density of p-CREB was markedly attenuated compared to controls, and this attenuation persisted 3 weeks after withdrawal from delta9-THC. These data provide evidence for the involvement of cerebellar granule cells in the adaptive changes occurring during acute and chronic delta9-THC exposure. This might be a mechanism by which delta9-THC interferes with motor and cognitive functions.

  4. Morphological and Phagocytic Profile of Microglia in the Developing Rat Cerebellum1,2,3

    PubMed Central

    VanRyzin, Jonathan W.

    2015-01-01

    Abstract Microglia are being increasingly recognized as playing important roles in neurodevelopment. The cerebellum matures postnatally, undergoing major growth, but the role of microglia in the developing cerebellum is not well understood. Using the laboratory rat we quantified and morphologically categorized microglia throughout the vermis and across development using a design-based unbiased stereology method. We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner. These morphological changes were accompanied by the sudden appearance of phagocytic cups during the third postnatal week from P17 to P19, with an approximately fourfold increase compared with the first week, followed by a prompt decline at the end of the third week. The microglial phagocytic cups were significantly higher in the granular layer (∼69%) than in the molecular layer (ML; ∼31%) during a 3 d window, and present on ∼67% of microglia with thick processes and ∼33% of microglia with thin processes. Similar proportions of phagocytic cups associated to microglia with either thick or thin processes were found in the ML. We observed cell nuclei fragmentation and cleaved caspase-3 expression within some microglial phagocytic cups, presumably from dying granule neurons. At P17 males showed an approximately twofold increase in microglia with thin processes compared with females. Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum. PMID:26464992

  5. Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise

    PubMed Central

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Holschneider, Daniel P.

    2015-01-01

    Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson’s disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4 weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [14C]-iodoantipyrine 1 week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. PMID:25747184

  6. Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

    PubMed

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

    2015-05-01

    Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function.

  7. [Lipid parameters of the skin, cerebellum, and medulla oblongata during immersion stress in rats].

    PubMed

    Gribanov, G A; Kostiuk, N V; Abramov, Iu V; Bykov, V A; Rebrov, L B; Volodina, T V; Pertsov, S S

    1999-01-01

    The influence of short-form water immersion stress of rats on lipids in the skin, the cerebellum and the medulla oblongata was studied. The level of total lipids and absolute and relative contents of the main lipid fractions (phospholipids, nonesterified cholesterol, free fatty acids, triglycerides, and cholesterol esters) were measured. Stress induced delayed changes of the lipid component of the skin. The first significant changes of lipid fractions were only observed 20 h later after the stress procedure. These changes were retained (being at nearly constant levels) till the end of the second day. The decrease in contents of total lipids and esterified cholesterol was revealed in the cerebellum of stressed rats (in comparison to these levels in control rats). These results suggest the involvement of cholesterol metabolic system in the stress reaction. The content of total lipids decreased also in the medulla oblongata. However, levels of the main lipid fractions changed differently. The content of diglycerides increased and the content of cholesterol decreased. The data obtained suggest that degradation of triglycerides is the principle pathway of metabolic conversions of lipids. Free fatty acids formed during these processes are probably involved in the synthesis of phospholipids and cholesterol esters. The data indicate absolutely different mechanisms of interrelations between individual lipid fractions in the brain regions studied. Various roles of the brain structures in the stress response of the body may account for the differences revealed.

  8. Effect of coadministration of neurovite and Lamivudine on the histomorphology of the cerebellum of wistar rats.

    PubMed

    Peter, A I; Ekong, M B; Davies, K; Azu, O O; Bassey, R B; Ugwu, L O; Umoh, I U

    2014-01-01

    Introduction. Lamivudine is a nucleoside reverse transcriptase inhibitor antiretroviral agent used in the treatment of human immunodeficiency virus type 1 infection. This study was to investigate the effects of coadministration of neurovite and lamivudine on the histomorphology of the cerebellum of Wistar rats. Materials and Methods. Twenty Wistar rats were divided equally into four groups. Group A animals were the control treated with distilled water. Groups B, C, and D animals were treated, respectively, with therapeutic dose of lamivudine (4.28 mg/kg), a combination of lamivudine (4.28 mg/kg) and neurovite (7.05 mg/kg), and neurovite (7.05 mg/kg) alone, daily. The rats were sacrificed using chloroform inhalation, processed, and stained using H&E method. Results. There was severe cellular degeneration with dystrophic changes, vacuolization in the molecular and granular layers, and aggregation of swollen Purkinje cells in group B animals compared with group C animals which showed only slight cellular dystrophy and inflammation. The mean cellular population was significantly (P < 0.05) higher in the treatment groups compared with the control. Conclusion. There was amelioration of damage of the cerebellum in the animals treated with neurovite and lamivudine combination compared to animals treated with only lamivudine. Therefore, there is need to give neurovite to patients on lamivudine therapy.

  9. Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats.

    PubMed

    Lechuga-Sancho, Alfonso M; Arroba, Ana I; Frago, Laura M; Pañeda, Covadonga; García-Cáceres, Cristina; Delgado Rubín de Célix, Arancha; Argente, Jesús; Chowen, Julie A

    2006-08-01

    Poorly controlled diabetes mellitus results in structural and functional changes in many brain regions. We demonstrate that in streptozotocin-induced diabetic rats cell death is increased and proliferation decreased in the cerebellum, indicating overall cell loss. Levels of both the proform and cleaved forms of caspases 3, 6 and 9 are increased, with no change in caspases 7, 8 or 12. Colocalization of glial fibrillary acidic protein (GFAP) and cleaved caspase 3 and GFAP in TUNEL-positive cells increased in diabetic rats. Changes in GFAP levels paralleled modifications in proliferating cell nuclear antigen (PCNA), increasing at 1 week of diabetes and decreasing thereafter, and proliferating GFAP-positive cells were decreased in the cerebellum of diabetic rats. These results suggest that astrocytes are dramatically affected in the cerebellum, including an increase in cell death and a decrease in proliferation, and this could play a role in the structural and functional changes in this brain area in diabetes.

  10. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

    PubMed Central

    Hernández-Fonseca, Juan P.; Rincón, Jaimar; Pedreañez, Adriana; Viera, Ninoska; Arcaya, José L.; Carrizo, Edgardo; Mosquera, Jesús

    2009-01-01

    Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral. PMID:19812703

  11. Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

    PubMed Central

    López-Pedrajas, Rosa; Ramírez-Lamelas, Dolores T.; Muriach, Borja; Sánchez-Villarejo, María V.; Almansa, Inmaculada; Vidal-Gil, Lorena; Romero, Francisco J.; Barcia, Jorge M.; Muriach, María

    2015-01-01

    Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction. PMID:26283916

  12. [Age-related changes in activity of cerebellum Purkinje cells, shape of the complex spike, and locomotion of wistar rats under effect of ethanol].

    PubMed

    Karelina, T V

    2012-01-01

    The work deals with study of peculiarities of effect of ethanol upon the Purkinje cell activity, shape of the complex spike, and locomotion of rats at different stages of ontogenesis, such as the stage of the morphofunstional maturation of the cerebellar cortex, the mature stage, and in the process of aging. The experiments were carried out on three age groups of Wistar rats: rat pups (2 weeks), adult rats (3-6 months), and senile animals (22-26 months). The administration of ethanol has been established to produce an increase in frequency of simple spikes, a decrease in frequency of complex spikes, a shortening of duration of depression of simple spikes, a decrease in the total duration of the complex spike, the number and frequency of its impulses as well as reduction of the motor activity of animals of all age groups. The change of the majority of the studied parameters occurred by the common temporal scheme. The earliest responding were the rat pups, later--the adult rats, and the last--the animals of the senior group. The stronger effect of ethanol was observed in adult rats. Their differences of all studied parameters, as compared with rat pups and senile animals, were characterized on the whole by the longer period of time and by the higher percent of changes relative to the initial values. Analysis of the obtained results has shown that the most pronounced changes in parameters of the cerebellum Purkinje cell activity and of the complex spike shape corresponded to the more significant decrease in the locomotion level, i. e., were recorded in adult rats. Thus, the work has demonstrated different sensitivity to administration of ethanol in the Wistar rats at different stages of ontogenetic development.

  13. Radiation induces progenitor cell death, microglia activation, and blood-brain barrier damage in the juvenile rat cerebellum

    PubMed Central

    Zhou, Kai; Boström, Martina; Ek, C. Joakim; Li, Tao; Xie, Cuicui; Xu, Yiran; Sun, Yanyan; Blomgren, Klas; Zhu, Changlian

    2017-01-01

    Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient’s quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82.9% of them died within 24 h after irradiation. Furthermore, irradiation induced oxidative stress, microglia accumulation, and inflammation in the cerebellum. Interestingly, blood-brain barrier damage and blood flow reduction was considerably more pronounced in the cerebellum compared to other brain regions. The cerebellar volume decreased by 39% and the migration of proliferating cells to the internal granule layer decreased by 87.5% at 16 weeks after irradiation. In the light of recent studies demonstrating that the cerebellum is important not only for motor functions, but also for cognition, and since treatment of posterior fossa tumors in children typically results in debilitating cognitive deficits, this differential susceptibility of the cerebellum to irradiation should be taken into consideration for future protective strategies. PMID:28382975

  14. Downregulation of Purkinje Cell Activity by Modulators of Small Conductance Calcium-Activated Potassium Channels In Rat Cerebellum

    PubMed Central

    Karelina, T. V.; Stepanenko, Yu. D.; Abushik, P. A.; Sibarov, D. A.; Antonov, S. M.

    2016-01-01

    Small-conductance calcium-activated potassium channels (SK channels) are widely expressed in CNS tissues. Their functions, however, have not been well studied. Participation of SK channels in Purkinje cell (PC) pacemaker activity has been studied predominantly in vitro. Here we studied for the first time the effects of SK channel activation by NS309 or CyPPA on the PC simple spike frequency in vivo in adult (3 – 6 months) and aged (22 – 28 months) rats using extracellular microelectrode recordings. Both pharmacological agents caused a statistically significant decrease in the PC simple spike frequency. The maximum value of the decrease in the simple spike frequency did not depend on age, whereas a statistically significant inhibition of the spike frequency was achieved faster in aged animals than in adult ones. In experiments on cultured neurons PCs were identified by the expression of calbindin as the PC-specific marker. Registration of transmembrane currents in cerebellar neurons revealed the direct action of NS309 and CyPPA on the SK channels of PC consisted in the enhancement of outward potassium currents and action potential after-hyperpolarization. Thus, SK channel activators can compensate for age-related changes of the autorhythmic functions of the cerebellum. PMID:28050270

  15. KCTD11 expression in medulloblastoma is lower than in adult cerebellum and higher than in neural stem cells.

    PubMed

    Zawlik, Izabela; Zakrzewska, Magdalena; Witusik, Monika; Golanska, Ewa; Kulczycka-Wojdala, Dominika; Szybka, Malgorzata; Piaskowski, Sylwester; Wozniak, Krystyna; Zakrzewski, Krzysztof; Papierz, Wielislaw; Liberski, Pawel P; Rieske, Piotr

    2006-10-01

    Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and the most frequent associated genetic alteration is loss of heterozygosity on chromosome region 7p13. Two genes mapping to this region, KCTD11 (alias REN) and HIC1, have been proposed as involved in MB pathogenesis. We used real-time polymerase chain reaction in 20 tissue samples of primary MB to examine the transcriptional level of the two genes, with reference to two types of controls: adult cerebellum and fetal neural stem cells. A significant reduction of KCTD11 expression relative to adult normal cerebellum was detected in 14 of 20 (70%) of MB samples. Neural stem cells had even lower levels of KCTD11 expression than did MB. HIC1 gene expression was low ( approximately 100 times lower than KCTD11 expression) in MB, and low also in both adult cerebellum and neural stem cells. Hypermethylation of the 5'UTR or the central region of HIC1 (or both) was detected in a significant number of MB samples, as well as in cerebellum and neural stem cells. Our data suggest that KCTD11 may play an important role in MB tumorigenesis, but do not support the role of HIC1 in this tumor development. We argue that recognition of the gene or genes important in MB tumorigenesis depends in part on defining an appropriate control.

  16. Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

    EPA Science Inventory

    Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

  17. Effect of dental amalgam on gene expression profiles in rat cerebrum, cerebellum, liver and kidney.

    PubMed

    Takahashi, Yoshifumi; Tsuruta, Shozo; Honda, Akiko; Fujiwara, Yasuyuki; Satoh, Masahiko; Yasutake, Akira

    2012-01-01

    Dental amalgam is a source of exposure to elemental mercury vapor in the general population. The aim of this study was to elucidate the effect of elemental mercury vapor exposure from dental amalgam restorations on gene expression profiles. Out of 26,962 rat genes, mercury vapor was found to increase the expression of 1 gene (Atp1b3) and decrease the expression of 1 gene (Tap1) in the cerebrum, increase the expression of 1 gene (Dnaja2) in the cerebellum, increase the expression of 2 genes (Actb and Timm23) and decrease the expression of 1 gene (Spink3) in the liver, increase the expression of 2 genes (RT1-Bb and Mgat5) and decrease the expression of 6 genes (Tnfaip8, Rara, Slc2a4, Wdr12, Pias4 and Timm13) in the kidney.

  18. Daily rhythms of benzodiazepine receptor numbers in frontal lobe and cerebellum of the rat

    SciTech Connect

    Brennan, M.J.W.; Volicer, L.; Moore-Ede, M.C.; Borsook, D.

    1985-06-17

    Behavioral, biochemical and neurophysiological evidence suggests that gamma-aminobutyric acid (GABA) may play an important role in the neural control of circadian rhythms. Central receptors for benzodiazepines are functionally coupled to GABA receptors and appear to mediate behavioral effects of exogenous benzodiazepines. The binding of /sup 3/H-flunitrazepam to synaptic plasma membranes prepared from various regions of rat brain was examined at 6-hour intervals over a 36-hour period. Prominent daily rhythms in receptor number (Bmax) were observed in the frontal lobe and the cerebellum but not in the temporoparietal regions, hypothalamus or medulla/pons. Binding was highest during periods of sleep/low activity with a significant decrease occurring just prior to waking. These results suggest that daily fluctuations in benzodiazepine receptor numbers may be related to the temporal control of sleep/wake and muscle activity cycles. 23 references, 1 figure, 1 table.

  19. Fos expression at the cerebellum following non-contact arousal and mating behavior in male rats

    PubMed Central

    Manzo, Jorge; Miquel, Marta; Toledo, Rebeca; Mayor-Mar, Justo Abraham; Garcia, Luis I.; Aranda-Abreu, Gonzalo E.; Caba, Mario; Hernandez, Maria Elena

    2010-01-01

    The cerebellum is considered a center underlying fine movements, cognition, memory and sexual responses. The latter feature led us to correlate sexual arousal and copulation in male rats with neural activity at the cerebellar cortex. Two behavioral paradigms were used in this investigation: the stimulation of males by distant receptive females (non-contact sexual stimulation), and the execution of up to three consecutive ejaculations. The vermis area of the cerebellum was removed following behavioral experiments, cut into sagittal sections, and analyzed with Fos immunohistochemistry to determine neuronal activation. At the mid-vermis region (sections from the midline to 0.1 mm laterally), non-contact stimulation significantly increased the activity of granule neurons. The number of activated cells increased in every lobule, but lobules 1 and 6 to 9 showed the greatest increment. In sexual behavior tests, males reaching one ejaculation had a high number of activated neurons similar to those counted after non-contact stimulation. However, two or three consecutive ejaculations showed a smaller number of Fos-ir cells. In contrast to the mid-vermis region, sections farthest from the midline (0.1 to 0.9 mm laterally) revealed that only lobule 7 expressed activated neurons. These data suggest that a well-delineated group of granule neurons have a sexual biphasic response at the cerebellar vermis, and that Fos in them is under an active degradation mechanism. Thus, they participate as a neural substrate for male rat sexual responses with an activation-deactivation process corresponding with the sensory stimulation and motor performance occurring during copulation. PMID:17936859

  20. The Proteome Profiles of the Cerebellum of Juvenile, Adult and Aged Rats—An Ontogenetic Study

    PubMed Central

    Wille, Michael; Schümann, Antje; Wree, Andreas; Kreutzer, Michael; Glocker, Michael O.; Mutzbauer, Grit; Schmitt, Oliver

    2015-01-01

    In this study, we searched for proteins that change their expression in the cerebellum (Ce) of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better characterization of the microenvironment and its development may result from these study findings. A differential two-dimensional polyacrylamide gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of the samples revealed that the number of proteins of the functional classes differed depending on the developmental stages. Especially members of the functional classes of biosynthesis, regulatory proteins, chaperones and structural proteins show the highest differential expression within the analyzed stages of development. Therefore, members of these functional protein groups seem to be involved in the development and differentiation of the Ce within the analyzed development stages. In this study, changes in the expression of proteins in the Ce at different postnatal developmental stages (postnatal days (P) 7, 90, and 637) could be observed. At the same time, an identification of proteins which are involved in cell migration and differentiation was possible. Especially proteins involved in processes of the biosynthesis and regulation, the dynamic organization of the cytoskeleton as well as chaperones showed a high amount of differentially expressed proteins between the analyzed dates. PMID:26370973

  1. Electrophysiological Characterization of The Cerebellum in the Arterially Perfused Hindbrain and Upper Body of The Rat

    PubMed Central

    Rawson, John A.; Apps, Richard

    2009-01-01

    In the present study, a non-pulsatile arterially perfused hindbrain and upper body rat preparation is described which is an extension of the brainstem preparation reported by Potts et al., (Brain Res Bull 53(1):59–67), 1. The modified in situ preparation allows study of cerebellar function whilst preserving the integrity of many of its interconnections with the brainstem, upper spinal cord and the peripheral nervous system of the head and forelimbs. Evoked mossy fibre, climbing fibre and parallel fibre field potentials and EMG activity elicited in forelimb biceps muscle by interpositus stimulation provided evidence that both cerebellar inputs and outputs remain operational in this preparation. Similarly, the spontaneous and evoked single unit activity of Purkinje cells, putative Golgi cells, molecular interneurones and cerebellar nuclear neurones was similar to activity patterns reported in vivo. The advantages of the preparation include the ability to record, without the complications of anaesthesia, stabile single unit activity for extended periods (3 h or more), from regions of the rat cerebellum that are difficult to access in vivo. The preparation should therefore be a useful adjunct to in vitro and in vivo studies of neural circuits underlying cerebellar contributions to movement control and motor learning. PMID:20033360

  2. Motor skill learning enhances the expression of activity-regulated cytoskeleton-associated protein in the rat cerebellum.

    PubMed

    Wang, Dean-Chuan; Lin, Yu-Yi; Chen, Tsan-Ju; Lin, Hwai-Ting

    2014-11-01

    Motor skill learning is essential for environmental adaptations during everyday life. It has been shown that the cerebellum plays an important role in both the adaptation of eye movements and the motor skill learning. However, the neuronal substrates responsible for consolidation of complex motor skills rather than simple reflexes are still uncertain. Because the induction of immediate-early genes activity-regulated cytoskeleton-associated protein (Arc) and zinc finger binding protein clone 268 (Zif268) has been regarded as a marker for recent neuronal activity, therefore, in the present study, a rat paradigm of motor skill learning was used to investigate the protein expression of Arc and zif268 in the cerebellum after motor skill learning. Rats were trained to traverse the runway apparatus for 5 days. Protein samples were collected from the cerebellar cortices 1 hour after the training on days 1, 3, and 5, and analyzed by western blotting. The results showed that the expression of Arc, but not zif268, was significantly increased in the cerebellum following motor skill learning. These findings suggest that motor skill learning induces Arc expression in the cerebellum, which may play a role in acquiring complex motor skills.

  3. Reduction of GABA/sub B/ receptor binding induced by climbing fiber degeneration in the rat cerebellum

    SciTech Connect

    Kato, K.; Fukuda, H.

    1985-07-22

    When the rat cerebellar climbing fibers degenerated, as induced by lesioning the inferior olive with 3-acetylpyridine (3-AP), GABA/sub B/ receptor binding determined with /sup 3/H-(+/-)baclofen was reduced in the cerebellum but not in the cerebral cortex of rats. Computer analysis of saturation data revealed two components of the binding sites, and indicated that decrease of the binding in the cerebellum was due to reduction in receptor density, mainly of the high-affinity sites, the B/sub max/ of which was reduced to one-third that in the control animals. In vitro treatment with 3-AP, of the membranes prepared from either the cerebellum or the cerebral cortex, induced no alteration in the binding sites, thereby indicating that the alteration of GABA/sub B/ sites induced by in vivo treatment with 3-AP is not due to a direct action of 3-AP on the receptor. GABA/sub A/ and benzodiazepine receptor binding labelled with /sup 3/H-muscimol and /sup 3/H-diazepam, respectively, in both of brain regions was not affected by destruction of the inferior olive. These results provide evidence that some of the GABA/sub B/ sites but neither GABA/sub A/ nor benzodiazepine receptors in the cerebellum are located at the climbing fiber terminals. 28 references, 4 figures, 2 tables.

  4. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

    SciTech Connect

    Silva, J.E.; Matthews, P.S.

    1984-09-01

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.

  5. Axonal motility and its modulation by activity are branch-type specific in the intact adult cerebellum

    PubMed Central

    Nishiyama, Hiroshi; Fukaya, Masahiro; Watanabe, Masahiko; Linden, David J.

    2007-01-01

    Summary We performed two-photon in vivo imaging of cerebellar climbing fibers (CFs; the terminal arbor of olivocerebellar axons) in adult mice. CF ascending branches innervate Purkinje cells while CF transverse branches show a near complete failure to form conventional synapses. Time-lapse imaging over hours or days revealed that ascending branches were very stable. However, transverse branches were highly dynamic, exhibiting rapid elongation and retraction and varicosity turnover. Thus, different branches of the same axon, with different innervation patterns, display branch type-specific motility in the adult cerebellum. Furthermore, dynamic changes in transverse branch length were almost completely suppressed by pharmacological stimulation of olivary firing. PMID:17988631

  6. Increase Signaling of Wnt/β-Catenin Pathway and Presence of Apoptosis in Cerebellum of Kindled Rats.

    PubMed

    Rubio-Osornio, Carmen; Rosiles-Abonce, Artemio; Trejo-Solís, Cristina; Rubio-Osornio, Moisés; Mendoza, Cesar; Custodio, Verónica; Martínez-Lazcano, Juan Carlos; González, Edith; Paz, Carlos

    2017-01-17

    Epilepsy is one of the most common neurological disorders in humans, and the role of the cerebellum in its physiopathology remains the subject of study. The Purkinje cells (PC), whose axons target the dentate and interpositus nuclei, form the main cerebellar output to forebrain structures involved in epilepsy. Cerebellar atrophy related to loss of PC has been reported in chronic epilepsy although its mechanism remains unclear. Taking in account that an overexpression of β-Catenin has been related with cell death, here we present the signaling of β-Catenin and the type of PC death in cerebellum of rats with chronic seizures induced by the amygdaloid kindling model. Using an immunohistochemistry and western blot assay for β-Catenin, c-Myc, cyclin D3, TUNEL and caspase-3, in rats chronically implanted with electrodes, receiving 0, 3, 15, and 45 electrical stimuli, we found that such rats suffering a major number of stimuli showed the highest amount of marks assessed. We concluded that there is higher activity of the Wnt/β-Catenin pathway associated with increased number of stimuli may be related with the presence of apoptosis in the cerebellum treated with amygdala kindling. In this way, we suggest this pathway as one of the mechanisms by which cerebellar neurons death in generalized seizures.

  7. Effects of cobalt on membrane ATPases, oxidant, and antioxidant values in the cerebrum and cerebellum of suckling rats.

    PubMed

    Garoui, Elmouldi; Ben Amara, Ibtissem; Driss, Dorra; Elwej, Awatef; Chaabouni, Semia Ellouze; Boudawara, Tahia; Zeghal, Najiba

    2013-09-01

    Chronic overexposure to cobalt (Co) may result in neurotoxic effects, but the mechanism of Co-induced neurotoxicity is not yet well established. Our study was conducted to determine whether Co is associated to the induction of central nervous system damage in pregnant rats and their progeny. Twelve pregnant female rats were randomly divided into 2 groups: group I served as controls and group II received Co (350 mg/L, orally). Treatments started from the 14th day of pregnancy until day 14 after delivery. Co concentration in plasma was higher in the treated groups than in the controls. Exposure to Co also increased the levels of MDA, PCO, H2O2, and AOPP, while Na(+)K(+)-ATPase and Mg(2+)-ATPase, AChE, and BuChE activities decreased in the cerebrum and cerebellum of suckling pups. A smear without ladder formation on agarose gel was also shown in the cerebrum and cerebellum, indicating random DNA degradation. A reduction in GPx, SOD, CAT, GSH, NPSH, and vitamin C values was observed. The changes were confirmed by histological results. In conclusion, these data showed that the exposure of pregnant and lactating rats to Co resulted in the development of oxidative stress and the impairment of defense systems in the cerebrum and cerebellum of their suckling pups.

  8. Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

    PubMed Central

    Kimura-Kuroda, Junko; Nishito, Yasumasa; Yanagisawa, Hiroko; Kuroda, Yoichiro; Komuta, Yukari; Kawano, Hitoshi; Hayashi, Masaharu

    2016-01-01

    Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs) relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children’s health. Here we examined the effects of long-term (14 days) and low dose (1 μM) exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p < 0.05, q < 0.05, ≥1.5 fold) between control cultures versus nicotine-, acetamiprid-, or imidacloprid-exposed cultures in 34, 48, and 67 genes, respectively. Common to all exposed groups were nine genes essential for neurodevelopment, suggesting that chronic neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain. PMID:27782041

  9. Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

    SciTech Connect

    Tacconi, M.T.; Salmona, M.

    1988-01-01

    To elucidate the relationship between the occupancy of BDZ binding sites and phospholipid methylation in brain, the authors examined phosphatidylethanolamine-N-methyltransferase (PEMT) activity in synaptosomes of rat hippocampi and cerebella in the presence of BDZ ligands with different modes of action. We found that Ro 5-4864, a specific ligand for peripheral type receptors, increased PL methylation in hippocampal and cerebellar synaptosomes. This effect was directly related to receptor occupancy, since the specific antagonist PK11195 inhibited the rise in PEMT activity induced by Ro 5-4864. Clonazepam, on the other hand, tended to reduce PL production in cerebellum and hippocampus except for hiccocampal (/sup 3/H)-phosphatidyl-N-monomethylethanolamine which was elevated by 40 to 70% at doses ranging from 10/sup -9/ to 10/sup -6/M. When equimolar concentrations of the antagonist Ro 15-1788 were given in association the clonazepam-induced phosphatidyl-N-monomethylethanolamine increase was reduced by 70%. These data support the involvement of structural and functional membrane alterations in the action of BDZ. 20 references, 2 figures, 2 tables.

  10. Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum.

    PubMed

    Kimura-Kuroda, Junko; Nishito, Yasumasa; Yanagisawa, Hiroko; Kuroda, Yoichiro; Komuta, Yukari; Kawano, Hitoshi; Hayashi, Masaharu

    2016-10-04

    Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs) relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children's health. Here we examined the effects of longterm (14 days) and low dose (1 μM) exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p < 0.05, q < 0.05, ≥1.5 fold) between control cultures versus nicotine-, acetamiprid-, or imidacloprid-exposed cultures in 34, 48, and 67 genes, respectively. Common to all exposed groups were nine genes essential for neurodevelopment, suggesting that chronic neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain.

  11. Fenthion, an organophosphorus pesticide, induces alterations in oxidant/antioxidant status and histopathological disorders in cerebrum and cerebellum of suckling rats.

    PubMed

    Ben Amara, Ibtissem; Sefi, Mediha; Troudi, Afef; Soudani, Nejla; Boudawara, Tahia; Zeghal, Najiba

    2014-08-01

    Fenthion (FEN) is an organophosphorus pesticide known for its wide toxic manifestations. In this study, the effects of FEN were evaluated on the cerebrum and cerebellum oxidant/antioxidant status and histopathological disorders in the suckling rats. Pregnant rats were divided into two groups: control group received pure water, while FEN group received daily by their drinking water 551 ppm of FEN from the 14th day of pregnancy until day 14 after delivery. Acetylcholine esterase (AChE) activity was inhibited in both the cerebrum and cerebellum of suckling rats whose mothers were treated with FEN. The cerebrum and cerebellum oxidative damage was demonstrated by a significant increase of malondialdehyde (MDA), advanced oxidation protein product and glutathione (GSH) levels and disturbance in the antioxidant enzyme activities. A significant decline of non-protein thiol and vitamin C levels was also observed. These changes were confirmed by histopathological observations which were marked by pyknotic neurons in the cerebrum and apoptotic cells in the cerebellum of FEN-treated rats. In the cerebellum of FEN-treated rats, the most conspicuous damage was the absence of external granular layer, indicating growth retardation. These data suggested that exposure of pregnant and lactating rats to FEN induced oxidative stress and histopathological disorders in the cerebrum and cerebellum of their pups. Thus, the use of FEN must be under strict control, especially for pregnant and lactating mothers.

  12. Early methyl donor deficiency alters cAMP signaling pathway and neurosteroidogenesis in the cerebellum of female rat pups

    PubMed Central

    El Hajj Chehadeh, Sarah; Dreumont, Natacha; Willekens, Jérèmy; Canabady-Rochelle, Laetitia; Jeannesson, Elise; Alberto, Jean-Marc; Daval, Jean-Luc; Guéant, Jean-Louis

    2014-01-01

    Early deficiency of the methyl donors folate and vitamin B12 produces hyperhomocysteinemia and cognitive and motor disorders in 21-day-old rat pups from dams fed a diet deficient in methyl donors during gestation and lactation. These disorders are associated with impaired neurogenesis and altered synaptic plasticity in cerebellum. We aimed to investigate whether these disorders could be related to impaired expression of neurosteroidogenesis-associated proteins, key regulator receptors, and some steroid content in the cerebellum. The methyl donor deficiency produced a decreased concentration of folate and vitamin B12, along with accumulation of homocysteine in Purkinje cells in both sexes, whereas the S-adenosylmethionine/S-adenosylhomocysteine ratio was reduced only in females. The transcription level and protein expression of StAR, aromatase, ERα, ERβ, and LH receptors were decreased only in females, with a marked effect in Purkinje cells, as shown by immunohistochemistry. Consistently, reduced levels of estradiol and pregnenolone were measured in cerebellar extracts of females only. The decreased expression levels of the transcriptional factors CREB, phospho-CREB, and SF-1, the lesser increase of cAMP concentration, and the lower level of phospho-PKC in the cerebellum of deficient females suggest that the activation of neurosteroidogenesis via cAMP-mediated signaling pathways associated with LHR activation would be altered. In conclusion, a gestational methyl donor deficiency impairs neurosteroidogenesis in cerebellum in a sex-dependent manner. PMID:25294213

  13. Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum

    PubMed Central

    Williams, Michael R; Fuchs, Jason R; Green, John T; Morielli, Anthony D

    2012-01-01

    The potassium channel Kv1.2 alpha-subunit is expressed in cerebellar Purkinje cell (PC) dendrites where its pharmacological inhibition increases excitability (Khavandgar et al., 2005). Kv1.2 is also expressed in cerebellar basket cell (BC) axon terminals (Sheng et al., 1994), where its blockade increases BC inhibition of PCs (Southan and Robertson, 1998a). Secretin receptors are also expressed both in PC dendrites and BC axon terminals (reviewed in (Yuan et al.). The effect of secretin on PC excitability is not yet known, but, like Kv1.2 inhibitors, secretin potently increases inhibitory input to PCs (Yung et al., 2001). This suggests secretin may act in part by suppressing Kv1.2. Receptor-mediated endocytosis is a mechanism of Kv1.2 suppression (Nesti et al., 2004). This process can be regulated by protein kinase A (PKA) (Connors et al., 2008). Since secretin receptors activate PKA (Wessels-Reiker et al., 1993), we tested the hypothesis that secretin regulates Kv1.2 trafficking in the cerebellum. Using cell surface protein biotinylation of rat cerebellar slices, we found secretin decreased cell-surface Kv1.2 levels by modulating Kv1.2 endocytic trafficking. This effect was mimicked by activating adenylate cyclase (AC) with forskolin, and was blocked by pharmacological inhibitors of AC or PKA. Imaging studies identified the BC axon terminal and Purkinje cell dendrites as loci of AC-dependent Kv1.2 trafficking. The physiological significance of secretin regulated Kv1.2 endocytosis is supported by our finding that infusion into the cerebellar cortex of either the Kv1.2 inhibitor Tityustoxin-Kα, or of the Kv1.2 regulator secretin, significantly enhances acquisition of eyeblink conditioning in rats. PMID:22764231

  14. Functional magnetic resonance imaging of the rat cerebellum during electrical stimulation of the fore- and hindpaw at 7 T

    NASA Astrophysics Data System (ADS)

    Peeters, Ronald; Verhoye, Marleen; Vos, Bart; De Schutter, Erik; Van der Linden, Anne-Marie

    1999-05-01

    Blood oxygenation level dependent contrast (BOLD) functional MRI responses at 7T were observed in the cerebellum of alpha- chloralose anesthetized rats in response to innocuous electrical stimulation of a forepaw or hindpaw. The responses were imaged in both coronal and sagittal slices which allowed for a clear delineation and localization of the observed activations. We demonstrate the validity of our fMRI protocol by imaging the responses in somatosensory cortex to the same stimuli and by showing a high level of reproducibility of the cerebellar responses. Widespread bilateral activations were found with mainly a patchy and medio-lateral band organization, more pronounced ipsilaterally. There was no overlap between the cerebellar activations caused by forepaw or hindpaw stimulation. Most remarkable was the overall horizontal organization of these responses: for both stimulation paradigms the patches and bands of activation were roughly positioned in either a cranial or caudal plane running antero-posteriorly through the whole cerebellum. This is the first fMRI study in the cerebellum of the rat. We relate our findings to the known projection patterns found with other techniques and to human fMRI studies. The horizontal organization found wasn't observed before in other studies using other techniques.

  15. [Determination of the N-acetylcysteine and methionine effects in the cerebellum of rats intoxicated with lead].

    PubMed

    Calderón-Cabrera, Lourdes; Durán-Galetta, María Gabriela; Garcia, Ingo; Galetta, Douglas; Lacruz, Luis; Naranjo, Raquel; Pérez, Beatriz; Ferreira, Elizabeth

    2008-03-01

    A therapeutic essay was done to determine the effects of N-Acetylcysteine (NAC), Methionine (MET) and the NAC + MET combination on the lead (Pb) blood levels, the malondialdehide (MDA) and catalase activity (CAT) in cerebellum of rats treated with 0.5 and 2 microg/g of Pb acetate. One hundred ninety eight male Wistar rats with an average weight of 240 g were subjected to a test, divided into five groups. Group 1 was the control group where basal levels were determined; Group 2 was the treated group; the rest of the groups once treated received the following: Group 3 NAC, Group 4 MET, Group 5 NAC + MET. The results showed that NAC lowers blood lead levels by 35% and 38% with intoxication doses of 0.5 microg/g and 2 microg/g of Pb acetate respectively. This decrease was not statistically significant; however, there was a 56% decrease of MDA in the cerebellum with a dose of 0.5 microg/g of Pb and of 75% with 2 microg/g; CAT activity increased in the cerebellum by 62% and 71% with the studied Pb doses, making this a statistically significant difference (p < 0.0001) in relation to the intoxication group. MET has a similar effect to NAC, even though it was less strong; anyhow, when NAC + MET are combined a quelant effect is shown, with a statistically significant 45% and 51% reduction in the Pb levels with the doses administered (p < 0.001); MDA decreased and CAT activity increased in the cerebellum. In this research we can conclude that NAC+MET when combined, have a beneficial effect on the studied parameters during acute Pb treatment.

  16. Increase in nitric oxide and cyclic GMP of rat cerebellum by radio frequency burst-type electromagnetic field radiation.

    PubMed Central

    Miura, M; Takayama, K; Okada, J

    1993-01-01

    1. Using rat cerebellum supernatant, the effects of radio frequency (RF) burst-type electromagnetic (EM) field radiation on the production of cyclic GMP were examined under various conditions. The radiation was generated by a generator coil, and set at a 10 MHz radiation frequency, a 50% burst time, a 10 kHz burst rate and a 5 V peak-to-peak generator voltage. 2. When the cerebellum supernatant was incubated with both exogenous L-arginine (nitric oxide (NO) donor) and NADPH, and irradiated by an RF burst-type EM field, the production of cyclic GMP was increased significantly from a level of 21-22 nmol min-1 (g tissue)-1 to 25-26 nmol min-1 (g tissue)-1. By contrast, such an effect was not found when the cerebellum supernatant was irradiated by an RF volley-type EM field. 3. When neither L-arginine nor NADPH were added to the cerebellum supernatant, the production of cyclic GMP was lowered to a level of 6 nmol min-1 (g tissue)-1 and the radiation effect was not found. When the cerebellum supernatant was chelated with EDTA, the production of cyclic GMP was lowered to a level of 7 nmol min-1 (g tissue)-1 and the radiation effect was not found. 4. Incubation with Methylene Blue, a guanylate cyclase inhibitor, lowered the production of cyclic GMP to a level of 10-12 nmol min-1 (g tissue)-1, and the radiation effect did not occur. On incubation with a NO synthase inhibitor, either NG-methyl-L-arginine or N omega-nitro-L-arginine methyl ester, the production of cyclic GMP was lowered to a level of 10-12 nmol min-1 (g tissue)-1 or 5-9 nmol min-1 (g tissue)-1 respectively, and the radiation effect was not observed. 5. Using electrochemical NO probes, the production of NO in the cerebellum supernatant was detected. The concentration of NO increased gradually after the onset of the EM field radiation. The radiation effect persisted, and reached a maximum after the cessation of the radiation. 6. In an in vivo study, the arterioles of the frog web were dilated by the radiation

  17. Properties of Na,K-ATPase in cerebellum of male and female rats: effects of acute and prolonged diabetes.

    PubMed

    Kaločayová, B; Mézešová, L; Barteková, M; Vlkovičová, J; Jendruchová, V; Vrbjar, N

    2017-01-01

    The present study was oriented to gender specificity of Na,K-ATPase in cerebellum, the crucial enzyme maintaining the intracellular homeostasis of Na ions in healthy and diabetic Wistar rats. The effects of diabetes on properties of the Na,K-ATPase in cerebellum derived from normal and streptozotocin (STZ)-diabetic rats of both genders were investigated. The samples were excised at different time intervals of diabetes induced by STZ (65 mg kg(-1)) for 8 days and 16 weeks. In acute 8-day-lasting model of diabetes, Western blot analysis showed significant depression of α1 isoform of Na,K-ATPase in males only. On the other hand, concerning the activity, the enzyme seems to be resistant to the acute model of diabetes in both genders. Prolongation of diabetes to 16 weeks was followed by increasing the number of active molecules of Na,K-ATPase exclusively in females as indicated by enzyme kinetic studies. Gender specificity was observed also in nondiabetic animals revealing higher Na,K-ATPase activity in control males probably caused by higher number of active enzyme molecules as indicated by increased value of V max when comparing to control female group. This difference seems to be age dependent: at the age of 16 weeks, the V max value in females was higher by more than 90%, whereas at the age of 24 weeks, this difference amounted to only 28%. These data indicate that the properties of Na,K-ATPase in cerebellum, playing crucial role in maintaining the Na(+) and K(+) gradients, depend on gender, age, and duration of diabetic impact.

  18. Treadmill exercise ameliorates motor dysfunction through inhibition of Purkinje cell loss in cerebellum of valproic acid-induced autistic rats

    PubMed Central

    Cho, Han-Sam; Kim, Tae-Woon; Ji, Eun-Sang; Park, Hye-Sang; Shin, Mal-Soon; Baek, Seung-Soo

    2016-01-01

    Autism is a complex developmental disorder with impairments in social interaction, communication, repetitive behavior and motor skills. Exercise enhances cognitive function, ameliorates motor dysfunction, and provides protective profits against neurodegeneration. In the present study, we evaluated the effect of treadmill exercise on the motor coordination and Purkinje cell loss in relation with reactive astrocytes and microglial activation in the cerebellum using valproic acid (VPA)-induced autism rat model. On the 12th day of pregnancy, the pregnant rats in the VPA-exposed group received intraperitoneal injections of 600-mg/kg VPA. After birth, the rat pups were divided into four groups: the control group, the exercise group, the VPA-treated group, the VPA-treated and exercise group. The rat pups in the exercise groups were forced to run on a treadmill for 30 min once a day, 5 times a week for 4 weeks. In the present results, motor balance and coordination was disturbed by induction of autism, in contrast, treadmill exercise alleviated motor dysfunction in the autistic rats. Purkinje cell loss, reactive astrocytes, and microglial activation were occurred by induction of autism, in contrast, treadmill exercise enhanced survival rate of Purkinje neurons through inhibition of reactive astrocytes and microglia in the autistic rats. The present study showed that exercise may provide a potential therapeutic strategy for the alleviation of motor dysfunction in autistic patients. PMID:27656625

  19. Cerebellum proteomics addressing the cognitive deficit of rats perinatally exposed to the food-relevant polychlorinated biphenyl 138.

    PubMed

    Campagna, Roberta; Brunelli, Laura; Airoldi, Luisa; Fanelli, Roberto; Hakansson, Helen; Heimeier, Rachel A; De Boever, Patrick; Boix, Jordi; Llansola, Marta; Felipo, Vicente; Pastorelli, Roberta

    2011-09-01

    Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in humans and laboratory animals by mechanisms that remain unknown. Recently, it has been shown that developmental exposure to 2,2',3,4,4',5'-hexachlorobiphenyl (PCB138), a food-relevant PCB congener, decreases the learning ability of young rats. The aim of this study was to characterize the effect of perinatal exposure to PCB138 on the brain proteome profile in young rats in order to gain insight into the mechanisms underlying PCB138 neurotoxicity. Comparison of the cerebellum proteome from 3-month-old unexposed and PCB138-exposed male offspring was performed using state-of-the-art label-free semiquantitative mass spectrometry method. Biological pathways associated with Ca(2+) homeostasis and androgen receptor signaling pathways were primarily disrupted. These perturbations may contribute toward a premature ageing-like proteome profile of the cerebellum that is triggered by PCB138 exposure in males. Our proteomic data provide insights into the phenomena that may be contributing to the PCB138 neurotoxicity effects observed in laboratory rodents and correlate with PCB exposure and decreased cognitive functions in humans. As such, this study highlights the importance of PCB138 as a risk factor in developmental neurotoxicity in laboratory rodents and humans.

  20. Early postnatal GFAP-expressing cells produce multilineage progeny in cerebrum and astrocytes in cerebellum of adult mice.

    PubMed

    Guo, Zhibao; Wang, Xijuan; Xiao, Jun; Wang, Yihui; Lu, Hong; Teng, Junfang; Wang, Wei

    2013-09-26

    Early postnatal GFAP-expressing cells are thought to be immature astrocytes. However, it is not clear if they possess multilineage capacity and if they can generate different lineages (astrocytes, neurons and oligodendrocytes) in the brain of adult mice. In order to identify the fate of astroglial cells in the postnatal brain, hGFAP-Cre-ER(T2) transgenic mice were crossed with the R26R Cre reporter mouse strains which exhibit constitutive expression of β-galactosidase (β-gal). Mice carrying the hGFAP-Cre-ER(T2)/R26R transgene were treated with Tamoxifen to induce Cre recombination in astroglial cells at postnatal (P) day 6 and Cre recombinase-expressing cells were identified by X-gal staining. Immunohistochemical staining was used to identify the type(s) of these reporter-tagged cells. Sixty days after recombination, X-gal-positive cells in different cerebral regions of the adult mice expressed the astroglial markers Blbp and GFAP, the neuronal marker NeuN, the oligodendrocyte precursor cell marker NG2 and the mature oligodendrocyte marker CC1. X-gal-positive cells in the cerebellum coexpressed the astroglial marker Blbp, but not the granule cell marker NeuN, Purkinje cell marker Calbindin or oligodendrocyte precursor cell marker NG2. Our genetic fate mapping data demonstrated that early postnatal GFAP-positive cells possessed multilineage potential and eventually differentiated into neurons, astrocytes, and oligodendrocyte precursor cells in the cerebrum and into astrocytes (including Bergmann glia) in the cerebellum of adult mice.

  1. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism.

    PubMed Central

    Silva, J E; Matthews, P S

    1984-01-01

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In euthyroid rats, fractional turnover rates of T3 per hour were: Cx, 0.26 +/- 0.02 (SE); Cm, 0.20 +/- 0.02; L, 0.98 +/- 0.07; R, 0.97 +/- 0.12; and the calculated unidirectional plasma T3 clearance by these tissues were, in milliliters per gram per hour: Cx = 0.38, Cm = 0.32, L = 5.0, and R = 5.6. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats. In the Cx, this response resulted from an approximately sixfold increase in fractional conversion and an approximately fourfold decrease in T3 removal rate hampered by a decreased uptake of T4 from plasma, whereas in Cm the response resulted only from the reduced T3 removal rate. In euthyroid rats, the

  2. Nitric Oxide Production in the Striatum and Cerebellum of a Rat Model of Preterm Global Perinatal Asphyxia.

    PubMed

    Barkhuizen, M; Van de Berg, W D J; De Vente, J; Blanco, C E; Gavilanes, A W D; Steinbusch, H W M

    2017-04-01

    Encephalopathy due to perinatal asphyxia (PA) is a major cause of neonatal morbidity and mortality in the period around birth. Preterm infants are especially at risk for cognitive, attention and motor impairments. Therapy for this subgroup is limited to supportive care, and new targets are thus urgently needed. Post-asphyxic excitotoxicity is partially mediated by excessive nitric oxide (NO) release. The aims of this study were to determine the timing and distribution of nitric oxide (NO) production after global PA in brain areas involved in motor regulation and coordination. This study focused on the rat striatum and cerebellum, as these areas also affect cognition or attention, in addition to their central role in motor control. NO/peroxynitrite levels were determined empirically with a fluorescent marker on postnatal days P5, P8 and P12. The distributions of neuronal NO synthase (nNOS), cyclic guanosine monophosphate (cGMP), astroglia and caspase-3 were determined with immunohistochemistry. Apoptosis was additionally assessed by measuring caspase-3-like activity from P2-P15. On P5 and P8, increased intensity of NO-associated fluorescence and cGMP immunoreactivity after PA was apparent in the striatum, but not in the cerebellum. No changes in nNOS immunoreactivity or astrocytes were observed. Modest changes in caspase-3-activity were observed between groups, but the overall time course of apoptosis over the first 11 days of life was similar between PA and controls. Altogether, these data suggest that PA increases NO/peroxynitrite levels during the first week after birth within the striatum, but not within the cerebellum, without marked astrogliosis. Therapeutic benefits of interventions that reduce endogenous NO production would likely be greater during this time frame.

  3. Disrupted cytoskeletal homeostasis, astrogliosis and apoptotic cell death in the cerebellum of preweaning rats injected with diphenyl ditelluride.

    PubMed

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Petenuzzo, Letícia; de Lima, Bárbara Ortiz; Fernandes, Carolina Gonçalves; da Rocha, João Batista Teixeira; Pessoa-Pureur, Regina

    2013-01-01

    In the present report 15 day-old rats were injected with 0.3μmol of diphenyl ditelluride (PhTe)(2)/kg body weight and parameters of neurodegeneration were analyzed in slices from cerebellum 3 and 6 days afterwards. The earlier responses, at day 3 after injection, included hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein - GFAP - and vimentin) and neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H); increased mitogen-activated protein kinase (MAPK) (Erk and p38MAPK) and cAMP-dependent protein kinase (PKA) activities. Also, reactive astrogliosis takes part of the early responses to the insult with (PhTe)(2), evidenced by upregulated GFAP in Western blot, PCR and immunofluorescence analysis. Six days after (PhTe)(2) injection we found persistent astrogliosis, increased propidium iodide (PI) positive cells in NeuN positive population evidenced by flow cytometry and reduced immunofluorescence for NeuN, suggesting that the in vivo exposure to (PhTe)(2) progressed to neuronal death. Moreover, activated caspase 3 suggested apoptotic neuronal death. Neurodegeneration was related with decreased [(3)H]glutamate uptake and decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was not altered in (PhTe)(2) injected rat. Therefore, the present results show that the earlier cerebellar responses to (PhTe)(2) include disruption of cytoskeletal homeostasis that could be related with MAPK and PKA activation and reactive astrogliosis. Akt inhibition observed at this time could also play a role in the neuronal death evidenced afterwards. The later events of the neurodegenerative process are characterized by persistent astrogliosis and activation of apoptotic neuronal death through caspase 3 mediated mechanisms, which could be related with glutamate excitotoxicity. The progression of these responses are therefore likely to be critical for the outcome of the neurodegeneration

  4. Aging and exercise affect the level of protein acetylation and SIRT1 activity in cerebellum of male rats.

    PubMed

    Marton, Orsolya; Koltai, Erika; Nyakas, Csaba; Bakonyi, Tibor; Zenteno-Savin, Tania; Kumagai, Shuzo; Goto, Sataro; Radak, Zsolt

    2010-12-01

    Aging is associated with a gradual decline in cognitive and motor functions, the result of complex biochemical processes including pre- and posttranslational modifications of proteins. Sirtuins are NAD(+) dependent protein deacetylases. These enzymes modulate the aging process by lysine deacetylation, which alters the activity and stability of proteins. Exercise can increase mean life-span and improve quality of life. Data from our laboratories revealed that 4 weeks of treadmill running improves performance in the Morris Maze test for young (4 months, old) but not old (30 months, old) male rats, and the exercise could not prevent the age-associated loss in muscle strength assessed by a gripping test. The positive correlation between protein acetylation and the gripping test suggests that the age-dependent decrease in relative activity of SIRT1 in the cerebellum impairs motor function. Similarly to the acetylation level of total proteins, the acetylation of ά -tubulin is also increased with aging, while the effect of exercise training was not found to be significant. Moreover, the protein content of nicotinamide phosphoribosyltransferase, one of the key enzymes of NAD biosynthesis, decreased in the young exercise group. These data suggest that aging results in decreased specific activity of SIRT1 in cerebellum, which could lead to increased acetylation of protein residues, including ά-tubulin, that interfere with motor function.

  5. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    NASA Technical Reports Server (NTRS)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

    1998-01-01

    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  6. Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Granado, Miriam; García-Cáceres, Cristina; Tuda, María; Frago, Laura M; Chowen, Julie A; Argente, Jesús

    2011-04-30

    Poorly controlled type1 diabetes is associated with hormonal imbalances and increased cell death in different tissues, including the pituitary, hypothalamus and cerebellum. In the pituitary, lactotrophs are the cell population with the greatest increase in cell death, whereas in the hypothalamus and cerebellum astrocytes are most highly affected. Insulin treatment can delay, but does not prevent, diabetic complications. As ghrelin and growth hormone (GH) secretagogues are reported to prevent apoptosis in different tissues, and to modulate glucose homeostasis, a combined hormonal treatment may be beneficial. Hence, we analyzed the effect of insulin and GH-releasing peptide 6 (GHRP-6) on diabetes-induced apoptosis in the pituitary, hypothalamus and cerebellum of diabetic rats. Adult male Wistar rats were made diabetic by streptozotocin injection (65 mg/kg ip) and divided into four groups from diabetes onset: those receiving a daily sc injection of saline (1 ml/kg/day), GHRP-6 (150 μg/kg/day), insulin (1-8U/day) or insulin plus GHRP-6 for 8 weeks. Control non-diabetic rats received saline (1 ml/kg/day). Diabetes increased cell death in the pituitary, hypothalamus and cerebellum (P<0.05). In the pituitary, insulin treatment prevented diabetes-induced apoptosis (P<0.01), as well as the decline in prolactin and GH mRNA levels (P<0.05). In the hypothalamus, neither insulin nor GHRP-6 decreased diabetes-induced cell death. However, the combined treatment of insulin+GHRP-6 prevented the diabetes induced-decrease in glial fibrillary acidic protein (GFAP) levels (P<0.05). In the cerebellum, although insulin treatment increased GFAP levels (P<0.01), only the combined treatment of insulin+ GHRP-6 decreased diabetes-induced apoptosis (P<0.05). In conclusion, insulin and GHRP-6 exert tissue specific effects in STZ-diabetic rats and act synergistically on some processes. Indeed, insulin treatment does not seem to be effective on preventing some of the diabetes-induced alterations

  7. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    SciTech Connect

    Kodavanti, Prasada Rao S.; Osorio, Cristina; Royland, Joyce E.; Ramabhadran, Ram; Alzate, Oscar

    2011-11-15

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta} (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant

  8. Metabolic mapping of the rat cerebellum during delay and trace eyeblink conditioning

    PubMed Central

    Plakke, Bethany; Freeman, John H.; Poremba, Amy

    2008-01-01

    The essential neural circuitry for delay eyeblink conditioning has been largely identified, whereas much of the neural circuitry for trace conditioning has not been identified. The major difference between delay and trace conditioning is a time gap between the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) during trace conditioning. It is this time gap or trace interval which accounts for an additional memory component in trace conditioning. Additional neural structures are also necessary for trace conditioning, including hippocampus and prefrontal cortex. This addition of forebrain structures necessary for trace but not delay conditioning suggests other brain areas become involved when a memory gap is added to the conditioning parameters. A metabolic marker of energy use, radioactively labeled glucose analog, was used to compare differences in glucose analog uptake between delay, trace, and unpaired experimental groups in order to identify new areas of involvement within the cerebellum. Known structures such as the interpositus nucleus and lobule HVI showed increased activation for both delay and trace conditioning compared to unpaired conditioning. However, there was a differential amount of activation between anterior and posterior portions of the interpositus nucleus between delay and trace, respectively. Cerebellar cortical areas including lobules IV and V of anterior lobe, Crus I, Crus II, and paramedian lobule also showed increases in activity for delay conditioning but not for trace conditioning. Delay and trace eyeblink conditioning both resulted in increased metabolic activity within the cerebellum but delay conditioning resulted in more widespread cerebellar cortical activation. PMID:17468019

  9. CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats.

    PubMed

    Das, Sutapa; Guha, Debjani

    2008-03-01

    Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.

  10. Fighting Oxidative Stress: Increased Resistance of Male Rat Cerebellum at Weaning Induced by Low Omega 6/Omega 3 Ratio in a Protein-Deficient Diet.

    PubMed

    Augusto, Ricielle Lopes; Isaac, Alinny Rosendo; Silva-Júnior, Ivanildo Inácio da; Santana, David Filipe de; Ferreira, Diorginis José Soares; Lagranha, Claudia Jacques; Gonçalves-Pimentel, Catarina; Rodrigues, Marcelo Cairrão Araujo; Andrade-da-Costa, Belmira Lara da Silveira

    2017-02-01

    The cerebellum is vulnerable to malnutrition effects. Notwithstanding, it is able to incorporate higher amount of docosahexaenoic acid (DHA) than the cerebral cortex (Cx) when low n-6/n-3 fatty acid ratio is present in a multideficient diet. Considering importance of DHA for brain redox balance, we hypothesize that this cerebellum feature improves its antioxidant status compared to the Cx. A chronic malnutrition status was induced on dams before mating and kept until weaning or adulthood (offspring). A group nutritionally rehabilitated from weaning was also analyzed. Morphometric parameters, total-superoxide dismutase (t-SOD) and catalase activities, lipoperoxidation (LP), nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, reactive oxygen species (ROS), and reduced nicotinamide adenine dinucleotide/phosphate levels were assessed. Both ROS and LP levels were increased (∼53 %) in the Cx of malnourished young animals while the opposite was seen in the cerebellum (72 and 20 % of the control, respectively). Consistently, lower (∼35 %) and higher t-SOD (∼153 %) and catalase (CAT) (∼38 %) activities were respectively detected in the Cx and cerebellum compared to the control. In malnourished adult animals, redox balance was maintained in the cerebellum and recovered in the Cx (lower ROS and LP levels and higher GSH/GSSG ratio). NO production was impaired by malnutrition at either age, mainly in the cerebellum. The findings suggest that despite a multinutrient deficiency and a modified structural development, a low dietary n-6/n-3 ratio favors early antioxidant resources in the male cerebellum and indicates an important role of astrocytes in the redox balance recovery of Cx in adulthood.

  11. Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

    PubMed

    Nowak, Przemyslaw; Jochem, Jerzy; Zwirska-Korczala, Krystyna; Josko, Jadwiga; Noras, Lukasz; Kostrzewa, Richard M; Brus, Ryszard

    2008-04-01

    To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity several-fold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum--reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

  12. Potential role of oxidative stress in mediating the effect of altered gravity on the developing rat cerebellum

    NASA Astrophysics Data System (ADS)

    Sajdel-Sulkowska, Elizabeth M.; Nguon, Kosal; Sulkowski, Zachary L.; Lipinski, Boguslaw

    We have previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that exposure to hypergravity results in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. To test this hypothesis we compared cerebellar oxidative stress markers 3-nitrotyrosine (3-NT; an index of oxidative protein modification) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an index of oxidative DNA damage) between stationary control (SC) and rat neonates exposed to 1.65 G (HG) on a 24-ft centrifuge from gestational day (G) 8 to postnatal day (P) 21. The levels of 3-NT and 8-OH-dG were determined by specific ELISAs. We also compared the Purkinje cell number (stereorologically) and rotarod performance between the two groups. The levels of 3-NT were increased only in HG females on P6 and on P12 in the cerebellum, and only in HG females on P12 in the extracellabellar tissue. Limited cerebellar data suggests an increase in the levels of 8-OH-dG on P12 only in HG females. In extracerebellar tissue the increase in 8-OH-dG levels was observed in both HG males and HG females except on P6 when it was only observed in HG males. While preliminary, these data suggest that the effect of hypergravity on the developing brain is sex-dependent and may involve oxidative stress. Oxidative stress may, in turn, contribute to the decrease Purkinje cell number and impaired motor behavior observed in hypergravity-exposed rats.

  13. An electrophysiological study of the in vitro, perfused brain stem-cerebellum of adult guinea-pig.

    PubMed Central

    Llinás, R; Mühlethaler, M

    1988-01-01

    1. We describe here a technique which allows the long-term in vitro survival of the perfused isolated brain stem-cerebellum of adult guinea-pig. The viability of this preparation was assessed by comparing the electrophysiological properties of individual neurones and of neuronal pools to those obtained in vivo or in brain slices. The areas investigated included the cerebellar cortex, the inferior olive and the pontine nuclei. 2. Cerebellar field potential and intra- and extracellular single-cell recordings could be obtained for as long as 15 h after the preparation was initially isolated. The waveforms of field potentials recorded at various depths in the cerebellar cortex following surface folial stimulation were similar to those recorded in vivo. Extracellular recordings from single Purkinje cells following white matter stimulation demonstrated antidromic as well as mossy- and climbing fibre-mediated excitation. Stimulation of the cerebellar surface elicited orthodromic parallel fibre excitation of Purkinje cells and basket-stellate and Golgi cell inhibition. 3. Intrasomatic and intradendritic recordings from Purkinje cells reproduced all the phenomenology described earlier under in vivo conditions and in vitro slice preparations. In addition, spontaneous excitatory synaptic potentials generating simple spikes (mossy fibre-parallel fibre-mediated activity) and complex spikes (climbing fibre-mediated activity) were consistently observed. 4. Extracellular field potentials and extra- and intracellular recordings from inferior olive neurones were similar to those previously shown for the mammalian inferior olive. 5. Intracellular recordings were also obtained from pontine nuclei neurones, a major source of mossy fibre afferents to the cerebellum. Stimulation of the contralateral superior cerebellar peduncle produced antidromic invasion of these neurones whereas stimulation of the ipsilateral inferior cerebral peduncle resulted in their orthodromic activation. 6. The

  14. Bacopa monnieri Extract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

    PubMed Central

    Mondal, Papia; Trigun, Surendra Kumar

    2015-01-01

    Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE. PMID:26413124

  15. Methylphenidate treatment leads to abnormalities on krebs cycle enzymes in the brain of young and adult rats.

    PubMed

    Réus, Gislaine Z; Scaini, Giselli; Furlanetto, Camila B; Morais, Meline O S; Jeremias, Isabela C; Mello-Santos, Lis Mairá; Freitas, Karolina V; Quevedo, João; Streck, Emilio L

    2013-08-01

    Studies have shown a relationship between energy metabolism and methylphenidate (MPH); however, there are no studies evaluating the effects of MPH in Krebs cycle. So, we investigated if MPH treatment could alter the activity of citrate synthase (CS), malate dehydrogenase (MD), and isocitrate dehydrogenase (ID) in the brain of young and adult Wistar rats. Our results showed that MPH (2 and 10 mg/kg) reduced CS in the striatum and prefrontal cortex (PF), with MPH at all doses in the cerebellum and hippocampus after chronic treatment in young rats. In adult rats the CS was reduced in the cerebellum after acute treatment with MPH at all doses, and after chronic treatment in the PF and cerebellum with MPH (10 mg/kg), and in the hippocampus with MPH (2 and 10 mg/kg). The ID decreased in the hippocampus and striatum with MPH (2 and 10 mg/kg), and in the cortex (10 mg/kg) after acute treatment in young rats. In adult rats acute treatment with MPH (2 and 10 mg/kg) reduced ID in the cerebellum, and with MPH (10 mg/kg) in the cortex; chronic treatment with MPH (10 mg/kg) decreased ID in the PF; with MPH (2 and 10 mg/kg) in the cerebellum, and with MPH at all doses in the hippocampus. The MD did not alter. In conclusion, our results suggest that MPH can alter enzymes of Krebs cycle in brain areas involved with circuits related with attention deficit hyperactivity disorder; however, such effects depend on age of animal and treatment regime.

  16. Amphiphysin I but not dynamin I nor synaptojanin mRNA expression increased after repeated methamphetamine administration in the rat cerebrum and cerebellum.

    PubMed

    Hamamura, Mitsuko; Okouchi, Jiro; Ozawa, Hidetoshi; Kimuro, Yoshihiko; Iwaki, Akiko; Fukumaki, Yasuyuki

    2013-07-01

    Dopamine increases/decreases synaptic vesicle recycling and in schizophrenia the proteins/mRNA is decreased. We isolated cDNA clone, similar to amphiphysin 1 (vesicle protein) mRNA from the neocortex of rats injected repeatedly with methamphetamine using polymerase chain reaction (PCR) differential display. This clone is highly homologous to the 3' region of the human amphiphysin gene. PCR extension study using a primer specific for the rat amphiphysin 1 gene and a primer located within the clone revealed that it is the 3' UTR region of the rat amphiphysin 1 gene. Furthermore, in situ hybridization revealed that amphiphysin 1 mRNA is expressed in the cerebrum, medial thalamus, hippocampus and cerebellum. In the cerebellum, amphiphysin mRNA expression was confined to upper granule cell layer. Repeated methamphetamine administration increased amphiphysin I mRNA expression in both anterior part of the cerebrum, and the cerebellum. However, the repeated administration did not alter mRNA expression of the other vesicle proteins, synaptotagmin I, synapsin I, synaptojanin and dynamin I, we conclude that the repeated administration selectively increased amphiphysin 1 mRNA expression. Thus, amphiphysin 1 does not work as synaptic recycling, but it is suggested, as a part of pathogenesis of brain tissue injury (under Ca²⁺ and Mg²⁺ devoid environment) in repeated methamphetamine-injected states, the gene regulate actin-asssembly, learning, cell stress signaling and cell polarity.

  17. Estradiol increases expression of the brain-derived neurotrophic factor after acute administration of ethanol in the neonatal rat cerebellum.

    PubMed

    Firozan, Bita; Goudarzi, Iran; Elahdadi Salmani, Mahmoud; Lashkarbolouki, Taghi; Rezaei, Arezou; Abrari, Kataneh

    2014-06-05

    Recently it has been shown that estradiol prevents the toxicity of ethanol in developing cerebellum. The neuroprotective effect of estradiol is not due to a single phenomenon but rather encompasses a spectrum of independent proccesses. According to the specific timing of Purkinje cell vulnerability to ethanol and several protective mechanisms of estradiol, we considered the neurotrophin system, as a regulator of differentiation, maturation and survival of neurons during CNS development. Interactions between estrogen and Brain derived neurotrophic factor (BDNF, an essential factor in neuronal survival) lead us to investigate involvement of BDNF pathway in neuroprotective effects of estrogen against ethanol toxicity. In this study, 17β-estradiol (300-900μg/kg) was injected subcutaneously in postnatal day (PD) 4, 30min prior to intraperitoneal injection of ethanol (6g/kg) in rat pups. Eight hours after injection of ethanol, BDNF mRNA and protein levels were assayed. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral tests in PD 23. Our results indicated that estradiol increased BDNF mRNA and protein levels in the presence of ethanol. We also observed that pretreatment with estradiol significantly attenuated ethanol-induced motoric impairment. Histological analysis also demonstrated that estradiol prevented Purkinje cell loss following ethanol treatment. These results provide evidence on the possible mechanisms of estradiol neuroprotection against ethanol toxicity.

  18. Role of Neurotrophins in Mediating the Effect of Altered Gravity on the Developing Rat Cerebellum.

    NASA Astrophysics Data System (ADS)

    Sajdel-Sulkowska, Elizabeth

    We previously reported that perinatal exposure to hypergravity resulted in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. However, the increase in oxidative stress markers was not uniformly observed in males and females. In the present study we explored the possibility that exposure to hypergravity may result in altered level of neurotrophins, which have been recognized as mediators of both neurodegenerative and neuroprotective mechanisms in the central nervous system. An elevation of neurotrophin-3 (NT-3) has been observed in animal models of hypoxia. To test this hypothesis we compared cerebellar levels of NT-3 between stationary control (SC) and rat neonates exposed perinatally to 1.65 G on a 24-ft centrifuge. The levels of NT-3 were determined by specific ELISA. Preliminary data suggests a 123

  19. Opposite effects of acute ethanol exposure on GAP-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats.

    PubMed

    Kulkarny, V V; Wiest, N E; Marquez, C P; Nixon, S C; Valenzuela, C F; Perrone-Bizzozero, N I

    2011-08-01

    The adolescent brain is particularly vulnerable to the effects of alcohol, with intoxications at this developmental age often producing long-lasting effects. The present study addresses the effects of a single acute ethanol exposure on growth-associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) gene expression in neurons in the cerebellum and hippocampus of adolescent rats. Male postnatal day 23 (P23) Sprague-Dawley rats were exposed to ethanol vapors for 2h and after a recovery period of 2h, the cerebellum and hippocampus were harvested and samples were taken for blood alcohol concentration (BAC) determinations. We found that this exposure resulted in a mean BAC of 174 mg/dL, which resembles levels in human adolescents after binge drinking. Analyses of total RNA and protein by quantitative reverse transcription PCR and western blotting, respectively, revealed that this single ethanol exposure significantly decreased the levels of GAP-43 mRNA and protein in the cerebellum but increased the levels of mRNA and protein in the hippocampus. BDNF mRNA and protein levels were also increased in the hippocampus but not in the cerebellum of these animals. In situ hybridizations revealed that GAP-43 and BDNF mRNA levels were primarily increased by alcohol exposure in hippocampal dentate granule cells and CA3 neurons. Overall, the reported alterations in the expression of the plasticity-associated genes GAP-43 and BDNF in juvenile rats are consistent with the known deleterious effects of binge drinking on motor coordination and cognitive function.

  20. Selective rather than inductive mechanisms favour specific replacement of Purkinje cells by embryonic cerebellar cells transplanted to the cerebellum of adult Purkinje cell degeneration (pcd) mutant mice.

    PubMed

    Carletti, Barbara; Rossi, Ferdinando

    2005-09-01

    Cell replacement after neuronal degeneration in the adult CNS depends on the availability of specific cues to direct specification, differentiation and integration of newly born neurons into mature circuits. Following recent reports indicating that neurogenic signals may be reactivated in the adult injured CNS, here we asked whether such signals are expressed in the cerebellum after Purkinje cell degeneration. Thus, we compared the fate of embryonic cerebellar cells transplanted to the cerebella of adult wild-type and Purkinje cell degeneration (pcd) mutant mice. Donor cells were dissected from beta-actin-enhanced green fluorescent protein (EGFP) transgenic mice and transplanted as a single cell suspension. In both hosts, grafted cells generated all major cerebellar phenotypes, with a precise localization in the recipient cortex or white matter. Nevertheless, the phenotypic distributions showed striking quantitative differences. Most notably, in the pcd cerebellum there was a higher amount of Purkinje cells, while other phenotypes were less frequent. Analysis of cell proliferation by 5-bromo-2'-deoxyuridine (BrDU) incorporation revealed that in both hosts mitotic activity was strongly reduced shortly after transplantation, and virtually all donor Purkinje cells were actually generated before grafting. Together, these results indicate that some compensatory mechanisms operate in the pcd environment. However, the very low mitotic rate of transplanted cells suggests that the adult cerebellum, either wild-type or mutant, does not provide instructive neurogenic cues to direct the specification of uncommitted progenitors. Rather, specific replacement in mutant hosts is achieved through selective mechanisms that favour the survival and integration of donor Purkinje cells at the expense of other phenotypes.

  1. Hydroxyurea Treatment and Development of the Rat Cerebellum: Effects on the Neurogenetic Profiles and Settled Patterns of Purkinje Cells and Deep Cerebellar Nuclei Neurons.

    PubMed

    Martí, Joaquín; Santa-Cruz, M C; Serra, Roger; Hervás, José P

    2016-11-01

    The current paper analyzes the development of the male and female rat cerebellum exposed to hydroxyurea (HU) (300 or 600 mg/kg) as embryo and collected at postnatal day 90. Our study reveals that the administration of this drug compromises neither the cytoarchitecture of the cerebellar cortex nor deep nuclei (DCN). However, in comparison with the saline group, we observed that several cerebellar parameters were lower in the HU injected groups. These parameters included area of the cerebellum, cerebellar cortex length, molecular layer area, Purkinje cell number, granule cell counts, internal granular layer, white matter and cerebellar nuclei areas, and number of deep cerebellar nuclei neurons. These features were larger in the rats injected with saline, smaller in those exposed to 300 mg/kg of HU and smallest in the group receiving 600 mg/kg of this agent. No sex differences in the effect of the HU were observed. In addition, we infer the neurogenetic timetables and the neurogenetic gradients of PCs and DCN neurons in rats exposed to either saline or HU as embryos. For this purpose, 5-bromo-2'-deoxyuridine was injected into pregnant rats previously administered with saline or HU. This thymidine analog was administered following a progressively delayed cumulative labeling method. The data presented here show that systematic differences exist in the pattern of neurogenesis and in the spatial location of cerebellar neurons between rats injected with saline or HU. No sex differences in the effect of the HU were observed. These findings have implications for the administration of this compound to women in gestation as the effects of HU on the development of the cerebellum might persist throughout their offsprings' life.

  2. Tetraethylammonium and 4-aminopyridine block calcium-dependent chloride current in rat cerebellum Purkinje cells.

    PubMed

    Zamoyski, V L; Vikhareva, E A; Grigoriev, V V; Bachurin, S O

    2016-09-01

    Using patch-clamp method (whole cell configuration), it was shown that tetraethylammonium (TEA) and 4-aminopyridine (4-AP) block calcium-dependent chloride currents in the membrane of freshly isolated cerebellar Purkinje cells of rats (12-15 days). In the concentration range studied (50 μM-10 mM TEA and 100 μM-1 mM 4-AP), both compounds blocked the chloride current at IC50 130 μM for TEA and 110 μM for 4-AP. TEA blockade was reversible after washing. The effect of 4-AP at concentrations greater than 100 μM was irreversible: both outward and inward chloride currents were blocked even after the removal of 4-AP from the incubation medium.

  3. Sex-comparative study of mouse cerebellum physiology under adult-onset hypothyroidism: The significance of GC-MS metabolomic data normalization in meta-analysis.

    PubMed

    Maga-Nteve, Christoniki; Vasilopoulou, Catherine G; Constantinou, Caterina; Margarity, Marigoula; Klapa, Maria I

    2017-01-15

    A systematic data quality validation and normalization strategy is an important component of the omic profile meta-analysis, ensuring comparability of the profiles and exclusion of experimental biases from the derived biological conclusions. In this study, we present the normalization methodology applied on the sets of cerebellum gas chromatography-mass spectrometry metabolic profiles of 124days old male and female animals in an adult-onset-hypothyroidism (AOH) mouse model before combining them into a sex-comparative analysis. The employed AOH model concerns the monitoring of the brain physiology of Balb/cJ mice after eight-week administration of 1%w/v KClO4 in the drinking water, initiated on the 60th day of their life. While originating from the same animal study, the tissues of the two sexes were processed and their profiles acquired and analyzed at different time periods. Hence, the previously published profile set of male mice was first re-annotated based on the presently available resources. Then, after being validated as acquired under the same analytical conditions, both profiles sets were corrected for derivatization biases and filtered for low-confidence measurements based on the same criteria. The final normalized 73-metabolite profiles contribute to the currently few available omic datasets of the AOH effect on brain molecular physiology, especially with respect to sex differentiation. Multivariate statistical analysis indicated one (unknown) and three (succinate, benzoate, myristate) metabolites with significantly higher and lower, respectively, cerebellum concentration in the hypothyroid compared to the euthyroid female mice. The respective numbers for the males were two and 24. Comparison of the euthyroid cerebellum metabolic profiles between the two sexes indicated 36 metabolites, including glucose, myo- and scyllo-inositol, with significantly lower concentration in the females versus the males. This implies that the female mouse cerebellum has been

  4. Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats.

    PubMed

    Perez-Pouchoulen, Miguel; Miquel, Marta; Saft, Paul; Brug, Brenda; Toledo, Rebeca; Hernandez, Maria Elena; Manzo, Jorge

    2016-10-01

    Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points. Testosterone has been linked to autism and plays an important role during brain development. Therefore, we identified and analyzed the androgen receptor (AR) by immunohistochemistry and densitometry, respectively. We found VPA decreases AR density in the superficial Purkinje layer only in cerebellar lobule 8 at PN7, but increased it at PN14 compared to control in males. In females, VPA decreased AR density in the superficial Purkinje layer in cerebellar lobule 6 at PN14, but increased it in lobule 9 at the same time point. No differences were found in the deep Purkinje layer of any cerebellar lobule in terms of AR density neither in males nor females. We additionally found a particular AR density decreasing in both superficial and deep regions across development in the majority of cerebellar lobules in males, but in all cerebellar lobules in females. Thus, our results indicate that VPA disrupts the AR ontogeny in the developing cerebellum in an age and region specific manner in male and female rats. Future epigenetic studies including the evaluation of histone deacetylases (HDAC's) might shed light these results as HDAC's are expressed by Purkinje neurons, interact with the AR and are VPA targets. This work contributes to the understanding of the cerebellar development and it might help to understand the role of the cerebellum in neurodevelopmental disorders such as autism.

  5. Effects of radiofrequency exposure on the GABAergic system in the rat cerebellum: clues from semi-quantitative immunohistochemistry.

    PubMed

    Mausset, A L; de Seze, R; Montpeyroux, F; Privat, A

    2001-08-31

    The widespread use of cellular phones raises the problem of interaction of electromagnetic fields with the central nervous system (CNS). In order to measure these effects on neurotransmitter content in the CNS, we developed a protocol of neurotransmitter detection based on immunohistochemistry and image analysis. Gamma-vinyl-GABA (GVG), an inhibitor of the GABA-transaminase was injected in rats to increase GABA concentration in the CNS. The cellular GABA contents were then revealed by immunohistochemistry and semi-quantified by image analysis thanks to three parameters: optical density (O.D.), staining area, and number of positive cells. The increase in cerebellar GABA content induced by GVG 1200 mg/kg was reflected in these three parameters in the molecular and the granular layers. Therefore, control of immunohistochemistry parameters, together with appropriate image analysis, allowed both the location and the detection of variations in cellular neurotransmitter content. This protocol was used to investigate the effects of exposure to 900 MHz radiofrequencies on cerebellar GABA content. Both pulsed emission with a specific absorption rate (SAR) of 4 W/kg and continuous emission with high SAR (32 W/kg) were tested. We observed a selective diminution of the stained processes area in the Purkinje cell layer after exposure to pulsed radiofrequency and, in addition, a decrease in O.D. in the three cell layers after exposure to continuous waves. Whether this effect is, at least partly, due to a local heating of the tissues is not known. Overall, it appears that high energetic radiofrequency exposure induces a diminution in cellular GABA content in the cerebellum.

  6. Morphological changes in cerebellum of neonatal rats exposed to 2. 45 GHz microwaves

    SciTech Connect

    Albert, E.N.; Sherif, M.

    1988-01-01

    One-day and six-day old Sprague-Dawley rats were exposed in the far field to 2.45 GHz (cw) microwaves at 10 mW/cm/sup 2/ for five consecutive days, 7 hours per day (SAR 2W/kg). Pups were euthenized one day after exposure and the cerebella processed for light and electron microscopy. Matching cerebellar sections and folia from irradiated and sham irradiated animals were examined. Light microscopic examination revealed the presence of small deeply-stained cells with hyperchromatic pyknotic nuclei within the external granular layer (EGL). The number of these pyknotic cells in the experimental animals was nearly twice that in the controls. The Nissl bodies in Purkinje cells were finely dispersed. In some experimental animals mononuclear cellular infiltration was demonstrated. Under the electron microscope the deeply-stained pyknotic small cells presented electron dense nuclei with clumped chromatin, extrusion or disintegration of the nucleus, ruptured nuclear membrane, and the vacuolization of the cytoplasm. Eventually these cells became phagocytosed by surrounding EGL cells. Most of the Purkinje cells of experimental animals showed small, disorderly arrays of rough endoplasmic reticulum (RER) instead of the typical orderly stacks of parallel arrays. These observations suggest that microwave radiation may interfere with early genesis of cerebellar microneurons and alter the metabolic status of Purkinje cells. However, this effect might be reversible.

  7. [Image and quantity analysis of prostaglandin in rats' blood plasma and Na(+)-K(+)-ATPase in their cerebellum during the prevention of motion sickness by cinnarizine].

    PubMed

    Dong, W; Tian, D; Zhang, M

    1998-06-01

    To study the mechanism of cinnarizine in preventing motion sickness, TXB2, 6-Keto-PGF1 alpha in rats' blood plasma and Na(+)-K(+)-ATPase activity in the endothelial cells of their cerebellar capillary were measured and analysed by a radioactive immunity analyser and a computer image system. The results showed that TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in the cinnarizine preventing group (CPG) decreased remarkably, compared with those in the motion sickness group(MSG) (p < 0.05). The activity of Na(+)-K(+)-ATPase in the endothelial cells of rats' cerebellar capillary in CPG was higher than that in MSG (p < 0.01). The authors suggest that the lower concentration of TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in CPG is closely related to cinnarizine which prevents Ca2+ from entering into the platelets and into the endothelial cells of blood vessels. The higher activity of Na(+)-K(+)-ATPase in the cerebellum may be caused by cinnarizene which dilates the blood vessels in the brain, increases the blood flow therein, and hinders Ca2+ from getting into the cerebellum cells. These change are believed to be the important mechanism of how cinnarizine prevents motion sickness.

  8. Dopamine D1 and D2 receptor functional down regulation in the cerebellum of hypoxic neonatal rats: neuroprotective role of glucose and oxygen, epinephrine resuscitation.

    PubMed

    Joseph, Binoy; Nandhu, M S; Paulose, C S

    2010-02-01

    Brain damage due to an episode of hypoxia remains a major problem in infants causing deficit in motor and sensory function. Molecular processes regulating the dopamine receptors play a very important role in motor and cognitive functions. Disturbances in the development of the dopaminergic system lead to dyskinesia, dystonia, tics and abnormal eye movements. The present study is to understand the hypoxic damage to the dopamine content and dopamine D(1), dopamine D(2) receptors in cerebellum and the neuroprotective effect of glucose supplementation prior to the current sequence of resuscitation-oxygen and epinephrine supplementation in neonatal rats. Dopamine content in the cerebellum showed a significant decrease in hypoxic neonatal rats when compared to control. Dopamine D(1) and dopamine D(2) receptors showed a decrease in B(max) during hypoxia. The cerebellar dopamine, dopamine D(1) and dopamine D(2) receptors showed significant decrease on supplementation of 100% oxygen alone to hypoxic rats when compared to control rats. Dopamine D(1) and dopamine D(2) receptors mRNA showed significant decrease during epinephrine supplementation prior to resuscitation. These dopaminergic receptor alterations were reversed to near control by glucose supplementation. Thus our results suggest that glucose acts as a neuroprotective agent in dopaminergic receptors function. This has immense clinical significance to correct the resuscitation sequence in neonatal care.

  9. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life.

  10. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

    PubMed Central

    da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings. PMID:26649198

  11. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats.

    PubMed

    da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS), protein oxidation (carbonyl), sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

  12. Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide A.

    PubMed

    Soman, Smijin; Anju, T R; Jayanarayanan, S; Antony, Sherin; Paulose, C S

    2013-06-01

    The aim of this study was to investigate the effect of Withania somnifera (WS) extract, withanolide A (WA), and carbamazepine (CBZ) on cerebellar AMPA receptor function in pilocarpine-induced temporal lobe epilepsy (TLE). In the present study, motor learning deficit was studied by rotarod test, grid walk test, and narrow beam test. Motor learning was significantly impaired in rats with epilepsy. The treatment with WS and WA significantly reversed the motor learning deficit in rats with epilepsy when compared with control rats. There was an increase in glutamate content and IP3 content observed in rats with epilepsy which was reversed in WS- and WA-treated rats with epilepsy. alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor dysfunction was analyzed using radiolabeled AMPA receptor binding assay, AMPA receptor mRNA expression, and immunohistochemistry using anti-AMPA receptor antibody. Our results suggest that there was a decrease in Bmax, mRNA expression, and AMPA receptor expression indicating AMPA receptor dysfunction, which is suggested to have contributed to the motor learning deficit observed in rats with epilepsy. Moreover, treatment with WS and WA resulted in physiological expression of AMPA receptors. There was also alteration in GAD and GLAST expression which supplemented the increase in extracellular glutamate. The treatment with WS and WA reversed the GAD and GLAST expression. These findings suggest that WS and WA regulate AMPA receptor function in the cerebellum of rats with TLE, which has therapeutic application in epilepsy.

  13. Assessment of oxidative stress in hippocampus, cerebellum and frontal cortex in rat pups exposed to lead (Pb) during specific periods of initial brain development.

    PubMed

    Barkur, Rajashekar Rao; Bairy, Laxminarayana Kurady

    2015-04-01

    Epidemiological studies in children have proved that lead (Pb) exposure causes deficits in neural and cognitive functions. The present study assessed the oxidative stress on postnatal day 30, in the hippocampus, cerebellum and frontal cortex of rat pups exposed to Pb during specific periods of early brain development. Five groups of rat pups were investigated, and 0.2% Pb acetate in drinking was the dosage used. (i) Gestation and lactation (GL) group (n = 9) of rat pups was exposed to Pb during gestation and lactation through their mother, (ii) gestation (G) group (n = 9) of rat pups was exposed to Pb during gestation only, (iii) lactation (L) group (n = 9) of rat pups was exposed to Pb during lactation only, (iv) pre-gestation (PG) group (n = 9) of rat pups was born to mothers who were exposed to Pb for 1 month before conception, and (v) normal control (NC) (n = 9) group of rats pups had no exposure to Pb during gestation and lactation period. From the present study, it is evident that Pb exposure during different periods of early brain development (GL, G, L and PG groups) causes oxidative stress and lactation period (postnatal period) of Pb exposure produces maximum oxidative stress.

  14. Polychlorinated biphenyls impair blood-brain barrier integrity via disruption of tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar rats: neuropotential role of quercetin.

    PubMed

    Selvakumar, K; Prabha, R Lakshmi; Saranya, K; Bavithra, S; Krishnamoorthy, G; Arunakaran, J

    2013-07-01

    Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances associated with carcinogenic and tumor-promoting effects as well as neurotoxic properties. Reactive oxygen species, which is produced from PCBs, alters blood-brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements and redistribution and disappearance of tight junction proteins (TJPs) like claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and other vegetables, appears to protect brain cells against oxidative stress, a tissue-damaging process associated with Alzheimer's and other neurodegenerative disorders. The aim of this study is to analyze the role of quercetin on oxidative stress markers and transcription of transmembrane and cytoplasmic accessory TJPs on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were divided into the following four groups. Group I: received only vehicle (corn oil) intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received quercetin alone gavage. From the experiment, the levels of hydrogen peroxide, lipid peroxidation and thiobarbituric acid reactive substances were observed to increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and 20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP in rats exposed to PCBs is decreased and is retrieved to the normal level simultaneously in quercetin-treated rats. Hence, quercetin can be used as a preventive medicine to PCBs exposure and prevents neurodegenerative disorders.

  15. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach.

    PubMed

    Sumathi, Thangarajan; Shobana, Chandrasekar; Thangarajeswari, Mohan; Usha, Ramakrishnan

    2015-01-01

    L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

  16. Apparent diffusion coefficient evaluation for secondary changes in the cerebellum of rats after middle cerebral artery occlusion.

    PubMed

    Yang, Yunjun; Gao, Lingyun; Fu, Jun; Zhang, Jun; Li, Yuxin; Yin, Bo; Chen, Weijian; Geng, Daoying

    2013-11-05

    Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffusion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially increased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion coefficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at remote regions (cerebellum) varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis.

  17. Loss of the calcium channel β4 subunit impairs parallel fibre volley and Purkinje cell firing in cerebellum of adult ataxic mice.

    PubMed

    Benedetti, Bruno; Benedetti, Ariane; Flucher, Bernhard E

    2016-06-01

    The auxiliary voltage-gated calcium channel subunit β4 supports targeting of calcium channels to the cell membrane, modulates ionic currents and promotes synaptic release in the central nervous system. β4 is abundant in cerebellum and its loss causes ataxia. However, the type of calcium channels and cerebellar functions affected by the loss of β4 are currently unknown. We therefore studied the structure and function of Purkinje cells in acute cerebellar slices of the β4 (-/-) ataxic (lethargic) mouse, finding that loss of β4 affected Purkinje cell input, morphology and pacemaker activity. In adult lethargic cerebellum evoked postsynaptic currents from parallel fibres were depressed, while paired-pulse facilitation and spontaneous synaptic currents were unaffected. Because climbing fibre input was spared, the parallel fibre/climbing fibre input ratio was reduced. The dendritic arbor of adult lethargic Purkinje cells displayed fewer and shorter dendrites, but a normal spine density. Accordingly, the width of the molecular and granular layers was reduced. These defects recapitulate the impaired cerebellar maturation observed upon Cav 2.1 ataxic mutations. However, unlike Cav 2.1 mutations, lethargic Purkinje cells also displayed a striking decrease in pacemaker firing frequency, without loss of firing regularity. All these deficiencies appear in late development, indicating the importance of β4 for the normal differentiation and function of mature Purkinje cells networks. The observed reduction of the parallel fibre input, the altered parallel fibre/climbing fibre ratio and the reduced Purkinje cell output can contribute to the severe motor impairment caused by the loss of the calcium channel β4 subunit in lethargic mice.

  18. Forced swimming test increases superoxide anion positive cells and angiotensin II positive cells in the cerebrum and cerebellum of the rat.

    PubMed

    Pedreanez, Adriana; Arcaya, Jose Luis; Carrizo, Edgardo; Mosquera, Jesus

    2006-12-11

    Situations of stress are capable of inducing depression and oxidative stress in the brain. Previous reports have shown that angiotensin II (Ang II) induces the production of superoxide anion (O(2)(-)), and impairment of endothelial function in cerebral microvessels in vivo. Substances that reduce angiotensin functions may be important in the treatment of depression. These data suggest a role for both Ang II and O(2)(-) in depression; thus, the aim of this study was to determine the effect of forced swimming test (FST), a model of stress/depression, on the cellular expression of Ang II and O(2)(-) in the central nervous system. To induce stress/depression, rats were subjected to FST daily (30 min) for 15 days. Unstressed animals were used as controls. Motor activity was automatically analyzed daily before swimming. Cerebrum and cerebellum frozen sections were studied for O(2)(-) by a histochemical method and for Ang II producing cells by a polyclonal antibody. In the FST group, struggle time, total horizontal activity, ambulatory movements, and vertical movements, were significantly decreased when the data from the 1st and 15th day were compared. Food intake and body weight gain also decreased when unstressed and FST rats were compared at the 15th day. Increased number of cerebrum and cerebellum O(2)(-), and Ang II positive cells, were observed in FST rats. Significant correlation was found between O(2)(-) positive cells and Ang II positive cell in the cerebrum. These results suggest that stress/depression situations could be involved in the increase of Ang II and oxidative stress in the central nervous system, with possible implications in the depressive condition.

  19. Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

    PubMed

    Sumathi, Thangarajan; Christinal, Johnson

    2016-07-01

    Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity.

  20. (1)H NMR-Based Metabolomics and Neurotoxicity Study of Cerebrum and Cerebellum in Rats Treated with Cinnabar, a Traditional Chinese Medicine.

    PubMed

    Wei, Lai; Xue, Rong; Zhang, Panpan; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

    2015-08-01

    Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. Nevertheless, the neurotoxic effects of cinnabar have also been noted. In this study, (1)H NMR-based metabolomics, combined with multivariate pattern recognition, were applied to investigate the neurotoxic effects of cinnabar after intragastrical administration (dosed at 2 and 5 g/kg body weight) on male Wistar rats. The metabolite variations induced by cinnabar were characterized by increased levels of glutamate, glutamine, myo-inositol, and choline, as well as decreased levels of GABA, taurine, NAA, and NAAG in tissue extracts of the cerebellum and cerebrum. These findings suggested that cinnabar induced glutamate excitotoxicity, neuronal cell loss, osmotic state changes, membrane fluidity disruption, and oxidative injury in the brain. We also show here that there is a dose- and time-dependent neurotoxicity of cinnabar, and that cerebellum was more sensitive to cinnabar induction than cerebrum. This work illustrates the utility and reliability of (1)H NMR-based metabolomics approach for examining the potential neurotoxic effects of cinnabar and other traditional Chinese medicines.

  1. Dose-related immunohistochemical and ultrastructural changes after oral methylphenidate administration in cerebrum and cerebellum of the rat.

    PubMed

    Bahcelioglu, Meltem; Gozil, Rabet; Take, Gulnur; Elmas, Cigdem; Oktem, Hale; Kadioglu, Dural; Calguner, Engin; Erdogan, Deniz; Sargon, Mustafa F; Yazici, A Canan; Tas, Murat; Bardakci, Yesim; Senol, Selahattin

    2009-01-01

    Methylphenidate is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder of children and young adults. Our aim is to investigate dose-dependent dopamine-2 receptor and glial fibrillary acidic protein expression and ultrastructural changes of the rat brain, to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female prepubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) were treated orally with methylphenidate dissolved in saline solution for 5 days per week during 3 months. At the end of the third month, tissues were removed and sections were collected for immunohistochemical and ultrastructural studies. We believe that methylphenidate causes dose-related activation of the dopaminergic system in several brain regions especially in ventral tegmental area and also causing neuronal degeneration and capillary wall structural changes such as basal membrane thickness and augmentation of the pinostatic vesicle in the endothelial cells. Also, increased dose of Ritalin is inducing astrocytes hypertrophy especially astrogliosis in pia-glial membrane and this is the result of the degenerative changes in prefrontal cortex region due to high dose methylphenidate administration. The dose-related accumulation of the astrocytes in capillary wall might well be a consequence of the need for nutrition of the neuronal tissue, due to transport mechanism deficiency related to neuronal and vascular degeneration. Thus, we believe that the therapeutic dose of methylphenidate must be kept in minimum level to prevent ultrastructural changes.

  2. Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats.

    PubMed

    Gomes, Karin M; Inácio, Cecília G; Valvassori, Samira S; Réus, Gislaine Z; Boeck, Carina R; Dal-Pizzol, Felipe; Quevedo, João

    2009-11-06

    The prescription of methylphenidate (MPH) has dramatically increased in this decade for attention deficit hyperactivity disorder (ADHD) treatment. The action mechanism of MPH is not completely understood and studies have been demonstrated that MPH can lead to neurochemical adaptations. Superoxide radical anion is not very reactive per se. However, severe species derived from superoxide radical anion mediate most of its toxicity. In this study, the superoxide level in submitochondrial particles was evaluated in response to treatment with MPH in the age-dependent manner in rats. MPH was administrated acutely or chronically at doses of 1, 2 or 10 mg/kg i.p. The results showed that the acute administration of MPH in all doses in young rats increased the production of superoxide in the cerebellum and only in the high dose (10mg/kg) in the hippocampus, while chronic treatment had no effect. However, acute treatment in adult rats had no effect on production of superoxide, but chronic treatment decreased the production of superoxide in the cerebellum at the lower doses. Our data suggest that the MPH treatment can influence on production of superoxide in some brain areas, but this effect depends on age of animals and treatment regime with MPH.

  3. Melanocytoma of cerebellum.

    PubMed

    Rai, S; Sharma, M; Naik, R; Sinha, R; Philipose, R; Verghese, R

    2008-01-01

    Melanocytomas are rare melanocytic tumors of the central nervous system. We report a rare case of melanocytoma in the cerebellum of a 35-year-old male patient. Computed tomography scan showed a cystic lesion with an enhancing solid component arising from the cerebellum. The lesion was resected and a histological diagnosis of melanocytoma of the cerebellum was made.

  4. [Transplantation of embryonic medulla oblongata into cerebella of adult rats].

    PubMed

    Nanami, T

    1989-01-01

    Pieces of medulla oblongata anlagen were dissected free from embryonic 13-20 day (E 13 to E 20) rat brain, and these were transplanted into the cerebellar vermis of adult rats (Fischer 344). After grafting, host animals survived for 4-9 months. Cytoarchitectonic organization of the graft and the relationship between host and graft were analyzed light microscopically in 34 animals using the Nissl and silver impregnation methods. Fine structures of the graft were analyzed in 4 animals using electron microscope. Grafts from E 13-14 donor tissue showed the highest survival rate (90%), which decreased as the donor embryonic age increased (i.e., E 15-16: 33%, E 17-20: 15%). In the surviving grafts, small (5-10 microns diameter), medium-sized (10-20 microns) and large (20-30 microns) neurons, whose cytoplasmic organelles appeared normal, were observed. Bundles of myelinated fibers traversed in every direction and neurons were often clustered, indicating characteristic features of the medulla oblongata. Electron microscopically, various types of synaptic formations were also observed. Degenerative profiles of nerve-fiber endings, containing dense bodies and lysosomal figures, were also seen. The degeneration seemed to be caused by the failure of their establishing connections with their proper targets in the host. In both the host tissue and the graft-host interface, neuronal processes apparently derived from the graft were frequently observed. Some axonal processes contained large-cored vesicles, and some dendritic processes were enlarged at their stalks and tips. Aberrant axon terminals of unmyelinated fibers in the host medullary layer were considered to be the graft origin. These fibers were always accompanied by prominent glial proliferation. There was no indication of forming myelinated fiber bundles that entered the host cerebellum from the donor tissue, although the former was the target of the latter. Cell bodies of host granule cells and oligodendroglia in the

  5. Down-regulation of phospholipase D2 mRNA in neonatal rat brainstem and cerebellum after hypoxia-ischemia.

    PubMed

    Peng, Jeng-Hsiung F; Feng, Yangzheng; Rhodes, Philip G

    2006-10-01

    Phospholipase D (PLD) and phosphatidylcholine (PC) were implicated in apoptosis and cancer. However, direct evidence on the role of PLD in the cause of apoptosis remains obscure. It was recently reported that apoptosis and necrosis could be induced in the cerebellum and brainstem after focal cerebral hypoxic-ischemic (HI) injury. It was found that apoptosis could be enhanced by farnesol inhibition of PLD signal transduction. Whereas it was shown that highly invasive cancer cell line depends on PLD activity for survival when deprived of serum growth factors. Based on these reports, it is postulated that apoptosis in the cerebellum and brainstem induced after focal cerebral HI treatment may be caused by faulty PLD expression. This is consistent with a report that PLD1 activity and mRNA levels were down-regulated during apoptosis. To test this hypothesis, Northern blotting was used to examine PLD2 mRNA expression after focal cerebral HI. The results show that both PLD2 mRNA 10.8 and 3.9 kb transcripts were significantly decreased by as much as 37% in the brainstem and cerebellum areas 3 h after HI compared to the control, concur with previous report of decreasing PLD activity after ischemia. These PLD2 transcripts, however, were not significantly different from the control 3 days after HI, indicating that the decrease in PLD2 transcription after HI maybe a transient phenomenon. This is the first report to show that the loss of membrane integrity resulting from deprivation of energy and growth factors after HI could cause decrease in PLD2 transcription that promotes apoptosis. The hypothetic role of PLD2 and the mechanism leading to apoptosis remains to be further elucidated.

  6. The Cerebellum, Sensitive Periods, and Autism

    PubMed Central

    Wang, Samuel S.-H.; Kloth, Alexander D.; Badura, Aleksandra

    2014-01-01

    Cerebellar research has focused principally on adult motor function. However, the cerebellum also maintains abundant connections with nonmotor brain regions throughout postnatal life. Here we review evidence that the cerebellum may guide the maturation of remote nonmotor neural circuitry and influence cognitive development, with a focus on its relationship with autism. Specific cerebellar zones influence neocortical substrates for social interaction, and we propose that sensitive-period disruption of such internal brain communication can account for autism's key features. PMID:25102558

  7. Development of the cerebellum and cerebellar neural circuits.

    PubMed

    Hibi, Masahiko; Shimizu, Takashi

    2012-03-01

    The cerebellum, a structure derived from the dorsal part of the most anterior hindbrain, is important for integrating sensory perception and motor control. While the structure and development of the cerebellum have been analyzed most extensively in mammals,recent studies have shown that the anatomy and development of the cerebellum is conserved between mammals and bony fish (teleost) species, including zebrafish. In the mammalian and teleost cerebellum,Purkinje and granule cells serve, respectively, as the major GABAergic and glutamatergic neurons. Purkinje cells originate in the ventricular zone (VZ), and receive inputs from climbing fibers. Granule cells originate in the upper rhombic lip (URL) and receive inputs from mossy fibers. Thus, the teleost cerebellum shares many features with the cerebellum of other vertebrates, and isa good model system for studying cerebellar function and development. The teleost cerebellum also has features that are specific to teleosts or have not been elucidated in mammals, including eurydendroid cells and adult neurogenesis. Furthermore, the neural circuitry in part of the optic tectum and the dorsal hindbrain closely resembles the circuitry of the teleost cerebellum; hence,these are called cerebellum-like structures. Here we describe the anatomy and development of cerebellar neurons and their circuitry, and discuss the possible roles of the cerebellum and cerebellum-like structures in behavior and higher cognitive functions. We also consider the potential use of genetics and novel techniques for studying the cerebellum in zebrafish.

  8. Distribution of constitutively expressed MEF-2A in adult rat and human nervous systems.

    PubMed

    Ruffle, Rebecca A; Mapley, Andrew C; Malik, Manmeet K; Labruzzo, Salvatore V; Chabla, Janet M; Jose, Riya; Hallas, Brian H; Yu, Han-Gang; Horowitz, Judith M; Torres, German

    2006-06-15

    Myocyte enhancer factor 2A (MEF-2A) is a calcium-regulated transcription factor that promotes cell survival during nervous system development. To define and further characterize the distribution pattern of MEF-2A in the adult mammalian brain, we used a specific polyclonal antiserum against human MEF-2A to identify nuclear-localized MEF-2A protein in hippocampal and frontal cortical regions. Western blot and immunocytochemical analyses showed that MEF-2A was expressed not only in laminar structures but also in blood vessels of rat and human brains. MEF-2A was colocalized with doublecortin (DCX), a microtubule-associated protein expressed by migrating neuroblasts, in CA1 and CA2 boundaries of the hippocampus. MEF-2A was expressed heterogeneously in additional structures of the rat brain, including the striatum, thalamus, and cerebellum. Furthermore, we found a strong nuclear and diffuse MEF-2A labeling pattern in spinal cord cells of rat and human material. Finally, the neurovasculature of adult rats and humans not only showed a strong expression of MEF-2A but also labeled positive for hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channels. This study further characterizes the distribution pattern of MEF-2A in the mammalian nervous system, demonstrates that MEF-2A colocalizes with DCX in selected neurons, and finds MEF-2A and HCN1 proteins in the neurovasculature network.

  9. Trains of epidural DC stimulation of the cerebellum tune corticomotor excitability.

    PubMed

    Oulad Ben Taib, Nordeyn; Manto, Mario

    2013-01-01

    We assessed the effects of anodal/cathodal direct current stimulation (DCS) applied epidurally over the cerebellum. We studied the excitability of both the motor cortex and the anterior horn of the spinal cord in adult rats under continuous anesthesia. We also investigated the effects on the spatial representation of a couple of agonist/antagonist muscles on primary motor cortex. Moreover, we evaluated the effects on the afferent inhibition in a paradigm of conditioned corticomotor responses. Anodal DCS of the cerebellum (1) decreased the excitability of the motor cortex, (2) reduced the excitability of F waves, as shown by the decrease of both mean F/mean M ratios and persistence of F waves, (3) exerted a "smoothing effect" on corticomotor maps, reshaping the representation of muscles on the motor cortex, and (4) enhanced the afferent inhibition of conditioned motor evoked responses. Cathodal DCS of the cerebellum exerted partially reverse effects. DCS of the cerebellum modulates the excitability of both motor cortex and spinal cord at the level of the anterior horn. This is the first demonstration that cerebellar DCS tunes the shape of corticomotor maps. Our findings provide a novel mechanism by which DCS of the cerebellum exerts a remote neuromodulatory effect upon motor cortex.

  10. Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined Extract of Purple Rice and Silkworm Pupae.

    PubMed

    Morakotsriwan, Nartnutda; Wattanathorn, Jintanaporn; Kirisattayakul, Woranan; Chaisiwamongkol, Kowit

    2016-01-01

    Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA) rat model of autism. VPA was injected on postnatal day (PND) 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg(-1) BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect.

  11. Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined Extract of Purple Rice and Silkworm Pupae

    PubMed Central

    Chaisiwamongkol, Kowit

    2016-01-01

    Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA) rat model of autism. VPA was injected on postnatal day (PND) 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg−1 BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect. PMID:27034733

  12. Metabolomic Method: UPLC-q-ToF Polar and Non-Polar Metabolites in the Healthy Rat Cerebellum Using an In-Vial Dual Extraction

    PubMed Central

    Thambisetty, Madhav; Parsons, Richard; Hye, Abdul; Legido-Quigley, Cristina

    2015-01-01

    Unbiased metabolomic analysis of biological samples is a powerful and increasingly commonly utilised tool, especially for the analysis of bio-fluids to identify candidate biomarkers. To date however only a small number of metabolomic studies have been applied to studying the metabolite composition of tissue samples, this is due, in part to a number of technical challenges including scarcity of material and difficulty in extracting metabolites. The aim of this study was to develop a method for maximising the biological information obtained from small tissue samples by optimising sample preparation, LC-MS analysis and metabolite identification. Here we describe an in-vial dual extraction (IVDE) method, with reversed phase and hydrophilic liquid interaction chromatography (HILIC) which reproducibly measured over 4,000 metabolite features from as little as 3mg of brain tissue. The aqueous phase was analysed in positive and negative modes following HILIC separation in which 2,838 metabolite features were consistently measured including amino acids, sugars and purine bases. The non-aqueous phase was also analysed in positive and negative modes following reversed phase separation gradients respectively from which 1,183 metabolite features were consistently measured representing metabolites such as phosphatidylcholines, sphingolipids and triacylglycerides. The described metabolomics method includes a database for 200 metabolites, retention time, mass and relative intensity, and presents the basal metabolite composition for brain tissue in the healthy rat cerebellum. PMID:25853858

  13. Altered Cerebellar Circuitry following Thoracic Spinal Cord Injury in Adult Rats

    PubMed Central

    2016-01-01

    Cerebellar function is critical for coordinating movement and motor learning. However, events occurring in the cerebellum following spinal cord injury (SCI) have not been investigated in detail. We provide evidence of SCI-induced cerebellar synaptic changes involving a loss of granule cell parallel fiber input to distal regions of the Purkinje cell dendritic tree. This is accompanied by an apparent increase in synaptic contacts to Purkinje cell proximal dendrites, presumably from climbing fibers originating in the inferior olive. We also observed an early stage injury-induced decrease in the levels of cerebellin-1, a synaptic organizing molecule that is critical for establishing and maintaining parallel fiber-Purkinje cell synaptic integrity. Interestingly, this transsynaptic reorganizational pattern is consistent with that reported during development and in certain transgenic mouse models. To our knowledge, such a reorganizational event has not been described in response to SCI in adult rats. Regardless, the novel results of this study are important for understanding SCI-induced synaptic changes in the cerebellum, which may prove critical for strategies focusing on promoting functional recovery. PMID:27504204

  14. Distribution of the inositol 1,4,5-trisphosphate receptor, P400, in adult rat brain.

    PubMed

    Rodrigo, J; Suburo, A M; Bentura, M L; Fernández, T; Nakade, S; Mikoshiba, K; Martínez-Murillo, R; Polak, J M

    1993-11-15

    The distribution of the inositol 1,4,5-trisphosphate receptor protein, P400, was investigated in adult rat brain by immunocytochemistry with the monoclonal antibody 4C11 raised against mouse cerebellar inositol 1,4,5-trisphosphate receptor protein. Immunoreactive neuronal cell bodies were detected in the cerebral cortex, the claustrum, the endopiriform nucleus, the corpus callosum, the anterior olfactory nuclei, the olfactory tubercle, the nucleus accumbens, the lateral septum, the bed nucleus of the stria terminalis, the hippocampal formation, the dentate gyrus, the caudate-putamen, the fundus striatum, the amygdaloid complex, the thalamus, the caudolateral part of the hypothalamus, the supramammillary nuclei, the substantia nigra, the pedunculopontine tegmental nucleus, the ventrotegmental area, the Purkinje cells in the cerebellum, the dorsal cochlear nucleus, the subnucleus oralis and caudalis of trigeminal nerve, and the dorsal horn of the spinal cord. Immunoreactive fibres were found in the medial forebrain bundle, the globus pallidus, the stria terminalis, the pyramidal tract, the spinal tract of trigeminal nerve, and the ventral horn of spinal cord. Nerve fibres forming a dense plexus ending in terminal-like boutons were detected in relation to nonimmunoreactive neurons of the dentate, interpositus, and fastigial nuclei of the cerebellum and around neurons of the vestibular nuclei. This receptor protein binds a specific second messenger, inositol 1,4,5-trisphosphate, which produces a mobilization of intracellular Ca2+ and a modulation of transmitter release.

  15. Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Ladd, B.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3rd week of pregnancy (G15 through birth on G22/G23; group B), the 1st week of nursing [birth through postnatal day (P) 6; group C], the 2nd and 3rd weeks of nursing (P6 through P21; group D), the combined 2nd and 3rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2nd and 3rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2nd and 3rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to

  16. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  17. Eyeblink Classical Conditioning and Interpositus Nucleus Activity Are Disrupted in Adult Rats Exposed to Ethanol as Neonates

    PubMed Central

    Green, John T.; Johnson, Timothy B.; Goodlett, Charles R.; Steinmetz, Joseph E.

    2002-01-01

    Neonatal exposure to ethanol in rats, during the period of brain development comparable to that of the human third trimester, produces significant, dose-dependent cell loss in the cerebellum and deficits in coordinated motor performance. These rats are also impaired in eyeblink conditioning as weanlings and as adults. The current study examined single-unit neural activity in the interpositus nucleus of the cerebellum in adults following neonatal binge ethanol exposure. Group Ethanol received alcohol doses of 5.25 g/kg/day on postnatal days 4–9. Group Sham Intubated underwent acute intragastric intubation on postnatal days 4–9 but did not receive any infusions. Group Unintubated Control (from separate litters) did not receive any intubations. When rats were 3–7 mo old, pairs of extracellular microelectrodes were implanted in the region of the interpositus nucleus. Beginning 1 wk later, the rats were given either 100 paired or 190 unpaired trials per day for 10 d followed by 4 d of 100 conditioned stimulus (CS)-alone trials per day. As in our previous study, conditioned response acquisition in Group Ethanol rats was impaired. In addition, by session 5 of paired acquisition, Group Sham Intubated and Group Unintubated Control showed significant increases in interpositus nucleus activity, relative to baseline, in the CS–unconditioned stimulus interval. In contrast, Group Ethanol failed to show significant changes in interpositus nucleus activity until later in training. These results indicate that the disruption in eyeblink conditioning after early exposure to ethanol is reflected in alterations in interpositus nucleus activity. PMID:12359839

  18. Inhibition of Na(+),K(+)-ATPase in the hypothalamus, pons and cerebellum of the offspring rat due to experimentally-induced maternal hypothyroidism.

    PubMed

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Tsela, Smaragda; Zissis, Konstantinos M; Kalafatakis, Konstantinos; Skandali, Nikolina; Voumvourakis, Konstantinos; Carageorgiou, Haris; Tsakiris, Stylianos

    2015-08-01

    Neurodevelopment is known to be particularly susceptible to thyroid hormone insufficiency and can result in extensive structural and functional deficits within the central nervous system (CNS), subsequently leading to the establishment of cognitive impairment and neuropsychiatric symptomatology. The current study evaluated the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive multilevel experimental approach to the study of hypothyroidism-induced changes that has been developed and characterized by the authors) on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a CNS region-specific manner. The activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking water) during the critical periods of neurodevelopment can result in an inhibition of hypothalamic, pontine and cerebellar Na(+),K(+)-ATPase; a major marker of neuronal excitability and metabolic energy production as well as an important regulator of important systems of neurotransmission. On the other hand, no significant changes in the activities of the herein offspring CNS regions' AChE and Mg(2+)-ATPase were recorded. The observed Na(+),K(+)-ATPase inhibition: (i) is region-specific (and non-detectable in whole brain homogenetes), (ii) could constitute a central event in the pathophysiology of clinically-relevant hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all examined experimental schemes, and (iv) certainly deserves further clarification at a molecular and histopathological level. As these findings are analyzed and compared to the available literature, they also underline the need for the adoption and further study of Na(+),K(+)-ATPase activity as a consistent neurochemical marker within the context of a systematic

  19. Ameliorative effect of Pimpinella anisum oil on immunohistochemical and ultrastuctural changes of cerebellum of albino rats induced by aspartame.

    PubMed

    Abdul-Hamid, Manal; Gallaly, Sanaa Rida

    2014-05-01

    The study aims to investigate the protective effect of Pimpinella anisum oil on aspartame (ASP) which resulted in cerebellar changes. The rats were divided into four equal groups: Group 1: (control group): served as control animals. Group 2: control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group): received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given orally to the animals by intra-gastric tube for 2 months. Group 4: received .5 mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h for 2 months. The histopathological approach revealed marked changes in the Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated animals. Some of these cells appeared with deeply stained cytoplasm. Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic reticulum and condensed mitochondria. Granular cells appeared with less c nuclei and surrounded by dissolution of most Mossy rosettes structures. Most myelinated nerve fibers showed thickening of myelinated sheath and others showed splitting of their myelin sheath. The histopathological, immunohistochemical and ultrastructural alterations were much less observed in concomitant use of P. anisum oil with ASP. Cerebellar cortex is considered target areas of ASP neurotoxicity, while P. anisum oil, when used in combination with ASP displays a protective action against neurotoxicity.

  20. Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells.

    PubMed

    Safina, Dina R; Surin, Alexander M; Pinelis, Vsevolod G; Kostrov, Sergey V

    2015-12-01

    Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT-3 and pro-NT-3 in this process remains unclear. The current study explores the effects of NT-3 and pro-NT-3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 µM) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT-3 had no effect on the induced changes in Ca²⁺ homeostasis. In contrast, pro-NT-3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca²⁺ concentration ([Ca²⁺]i ) and Fura-2 fluorescence quenching by Mn²⁺ within the first 20 sec of exposure to Glu, pro-NT-3 had no effect on the initial rate of Ca²⁺ entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca²⁺]i rise was 1.2-fold greater in the presence of pro-NT-3 than in the presence of Glu alone (1.67 ±  0.07 and 1.39 ± 0.04, respectively, P < 0.05). The Glu-induced changes in Са²⁺ homeostasis in the presence of pro-NT-3 likely are due to the decreased rate of Са²⁺ removal from the cytosol during the DCD latency period.

  1. Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects in adult rats.

    PubMed

    Bortel, Aleksandra; Słomian, Lucyna; Nitka, Dariusz; Swierszcz, Michał; Jaksz, Mirella; Adamus-Sitkiewicz, Beata; Nowak, Przemysław; Jośko, Jadwiga; Kostrzewa, Richard M; Brus, Ryszard

    2008-01-01

    To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by approximately 40% in the hippocampus and by approximately 20% in other brain regions at 1 h. Ethanol reduced GABA content by approximately 15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.

  2. Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

    PubMed

    Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

    2016-07-01

    Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction.

  3. Infections of the cerebellum.

    PubMed

    Pruitt, Amy A

    2014-11-01

    Although the cerebellum can be affected by any infection that also involves other parts of the brain parenchyma, cerebrospinal fluid, or nerve roots, a limited range of infections targets cerebellar structures preferentially. Thus, a primarily cerebellar syndrome narrows infectious differential diagnostic considerations. The differential diagnosis of rapidly evolving cerebellar signs suggesting infection includes prescription or illicit drug intoxications or adverse reactions, inflammatory pseudotumor, paraneoplastic processes, and acute postinfectious cerebellitis. This article discusses the diagnosis and differential diagnosis of viral, bacterial, fungal, and prion pathogens affecting the cerebellum in patterns predictable by pace of illness and by involved neuroanatomic structures.

  4. Cerebellum and apraxia.

    PubMed

    Mariën, Peter; van Dun, Kim; Verhoeven, Jo

    2015-02-01

    As early as the beginning of the nineteenth century, a variety of nonmotor cognitive and affective impairments associated with cerebellar pathology were occasionally documented. A causal link between cerebellar disease and nonmotor cognitive and affective disorders has, however, been dismissed for almost two centuries. During the past decades, the prevailing view of the cerebellum as a mere coordinator of autonomic and somatic motor function has changed fundamentally. Substantial progress has been made in elucidating the neuroanatomical connections of the cerebellum with the supratentorial association cortices that subserve nonmotor cognition and affect. Furthermore, functional neuroimaging studies and neurophysiological and neuropsychological research have shown that the cerebellum is crucially involved in modulating cognitive and affective processes. This paper presents an overview of the clinical and neuroradiological evidence supporting the view that the cerebellum plays an intrinsic part in purposeful, skilled motor actions. Despite the increasing number of studies devoted to a further refinement of the typology and anatomoclinical configurations of apraxia related to cerebellar pathology, the exact underlying pathophysiological mechanisms of cerebellar involvement remain to be elucidated. As genuine planning, organization, and execution disorders of skilled motor actions not due to motor, sensory, or general intellectual failure, the apraxias following disruption of the cerebrocerebellar network may be hypothetically considered to form part of the executive cluster of the cerebellar cognitive affective syndrome (CCAS), a highly influential concept defined by Schmahmann and Sherman (Brain 121:561-579, 1998) on the basis of four symptom clusters grouping related neurocognitive and affective deficits (executive, visuospatial, affective, and linguistic impairments). However, since only a handful of studies have explored the possible role of the cerebellum in

  5. Repeated corticosterone injections in adult mice alter stress hormonal receptor expression in the cerebellum and motor coordination without affecting spatial learning.

    PubMed

    Harlé, Guillaume; Lalonde, Robert; Fonte, Coralie; Ropars, Armelle; Frippiat, Jean-Pol; Strazielle, Catherine

    2017-03-02

    Receptors for glucocorticoid (GR) and corticotropin-releasing hormone (CRH) are largely found in brain sensorimotor structures, particularly in cerebellum, underlining a potential role of stress hormones in the regulation of motor function. Since CRH is involved in neuroplasticity, known for its trophic effect on synapses, we investigated how manipulations in corticosterone serum levels can modulate the CRH system in the cerebellum and affect motor coordination. Corticosterone at doses of either 15 or 30mg/kg was injected in mice and the status of hormonal expression evaluated in cerebellum, hippocampus, and hypothalamus in undisturbed housing conditions or after different behavioral tests. Under both conditions, metabolic activity in numerous brain regions involved in motor functions and emotion was measured by means of cytochrome oxidase (COX) activity labeling. After six consecutive days of corticosterone administration, CRH-R1 transcription was downregulated in hypothalamic and cerebellar regions and hypometabolic changes were observed in mice treated with the higher dose for several limbic and sensorimotor circuitries, notably basal ganglia, deep cerebellar nuclei, and red nucleus. Corticosterone did not modify motor activity, anxiety, and spatial orientation, but decreased latencies before falling from the rotorod and prevented mice from reaching targets in the coat-hanger test. In addition, COX activities were similar to control mice except in ventromedial thalamus and dorsal neostriatum, possibly indicating that physical activity protected brain energy metabolism against the stress hormone. The present findings showed that the CRH/CRH-R1 system might play a role in mediating the effects of stress on cerebellar function, affecting especially motor learning tasks.

  6. Ectocellular in vitro and in vivo metabolism of cADP-ribose in cerebellum.

    PubMed Central

    De Flora, A; Guida, L; Franco, L; Zocchi, E; Pestarino, M; Usai, C; Marchetti, C; Fedele, E; Fontana, G; Raiteri, M

    1996-01-01

    CD38, a type II transmembrane glycoprotein predominantly expressed in blood cells, is a bifunctional ectoenzyme directly involved in the metabolism of cADP-ribose (cADPR). This is a potent Ca2+ mobilizer in several types of cells. The relationship between the ectocellular site of cADPR production and its intracellular calcium-related functions is poorly understood. Cultured rat cerebellar granule cells showed both enzymic activities of CD38, ADP-ribosyl cyclase and cADPR hydrolase, at a ratio of 16 to 1 respectively, and were immunostained by the anti-(human CD38) monoclonal antibody IB4. In these cells externally added cADPR and beta-NAD+ (the precursor of cADPR), but not alpha-NAD+ or ADP-ribose, enhanced the peak of the depolarization-induced rise in intracellular Ca2+ concentration. This effect was inhibited by 1 microM ryanodine, suggesting a potentiation of calcium-induced calcium release by cADPR. CD38 ectoenzyme activities, ADP-ribosyl cyclase and cADPR hydrolase, were also demonstrated in vivo by microdialysis of adult rat cerebellum, where IB4 bound to granule neurons selectively. Trace amounts (11.5 +/- 3.8 nM) of NAD+ were detected by microdialysis sampling and sensitive assays in the basal interstitial fluid of the cerebellum. These results provide a link between ectocellular cADPR turnover and intracellular calcium mobilization in cerebellum. PMID:8973582

  7. Role of cerebellum in deglutition and deglutition disorders.

    PubMed

    Rangarathnam, Balaji; Kamarunas, Erin; McCullough, Gary H

    2014-12-01

    The objective of this review is to gather available evidence regarding the role of the cerebellum in swallowing-related functions. We reviewed literature on cerebellar functions related to healthy swallowing, patterns of dysphagia in individuals with cerebellar lesions, and the role of the cerebellum in therapeutic intervention of neurogenic dysphagia since 1980. A collective understanding of these studies suggests that both hemispheres of the cerebellum, predominantly the left, participate in healthy swallowing. Also, it appears that the cerebellum contributes to specific physiological functions within the entire act of swallowing, but this is not clearly understood. The understanding of patterns of dysphagia in cerebellar lesions remains ambiguous with equivocal results across a small number of studies. The cerebellum appears to be involved in oral exercises for dysphagia in the relationship between oral movements in such exercises, and deglutition remains uncertain. There is increasing evidence to suggest successful use of transcranial magnetic stimulation of the cerebellum to improve neuromotor control of swallowing. Future studies should address activation of the cerebellum with swallowing of different consistencies and tastes in healthy adults to gain better insights. Studies should also investigate dynamics of neural activation during different stages of recovery from dysphagia following strokes to cortical centers to determine if the cerebellum plays a compensatory role during instances of increased neural demands.

  8. Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty.

    PubMed

    Abdel-Rahman, Ali; Dechkovskaia, Anjelika M; Sutton, Jazmine M; Chen, Wei-Chung; Guan, Xiangrong; Khan, Wasiuddin A; Abou-Donia, Mohamed B

    2005-05-05

    Maternal smoking during pregnancy is known to be a significant contributor to developmental neurological health problems in the offspring. In animal studies, nicotine treatment via injection during gestation has been shown to produce episodic hypoxia in the developing fetus. Nicotine delivery via mini osmotic pump, while avoiding effects due to hypoxia-ischemia, it also provides a steady level of nicotine in the plasma. In the present study timed-pregnant Sprague-Dawley rats (300-350 g) were treated with nicotine (3.3 mg/kg, in bacteriostatic water via s.c. implantation of mini osmotic pump) from gestational days (GD) 4-20. Control animals were treated with bacteriostatic water via s.c. implantation of mini osmotic pump. Offspring on postnatal day (PND) 30 and 60, were evaluated for changes in the ligand binding for various types of nicotinic acetylcholine receptors and neuropathological alterations. Neurobehavioral evaluations for sensorimotor functions, beam-walk score, beam-walk time, incline plane and grip time response were carried out on PND 60 offspring. Beam-walk time and forepaw grip time showed significant impairments in both male and female offspring. Ligand binding densities for [3H]epibatidine, [3H]cytisine and [3H]alpha-bungarotoxin did not show any significant changes in nicotinic acetylcholine receptors subtypes in the cortex at PND 30 and 60. Histopathological evaluation using cresyl violet staining showed significant decrease in surviving Purkinje neurons in the cerebellum and a decrease in surviving neurons in the CA1 subfield of hippocampus on PND 30 and 60. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer of cerebellum and the CA1 subfield of hippocampus on PND 30 and 60 of both male and female offspring. These results indicate that maternal exposure to nicotine produces significant neurobehavioral deficits, a decrease in the surviving neurons and an

  9. Expression of doublecortin, a neuronal migration protein, in unipolar brush cells of the vestibulocerebellum and dorsal cochlear nucleus of the adult rat

    PubMed Central

    Manohar, Senthilvelan; Paolone, Nicholas A.; Bleichfeld, Marni; Hayes, Sarah; Salvi, Richard J.; Baizer, Joan S.

    2011-01-01

    Doublecortin (DCX) is a microtubule associated protein that is critical for neuronal migration and the development of the cerebral cortex. In the adult, it is expressed in newborn neurons in the subventricular and subgranular zones but not in the mature neurons of the cerebral cortex. By contrast, neurogenesis and neuronal migration of cells in the cerebellum continue into early postnatal life; migration of one class of cerebellar interneuron, unipolar brush cells (UBCs), may continue into adulthood. To explore the possibility of continued neuronal migration in the adult cerebellum, closely spaced sections through the brainstem and cerebellum of adult (3–16 months old) Sprague Dawley rats were immunolabeled for DCX. Neurons immunoreactive (ir) to DCX were present in the granular cell layer of the vestibulocerebellum, most densely in the transition zone (tz), the region between the flocculus (FL) and ventral paraflocculus (PFL), as well as in the dorsal cochlear nucleus (DCN). These DCX-ir cells had the morphological appearance of unipolar brush cells (UBCs) with oval somata and a single dendrite ending in a “brush.” There were many examples of colocalization of DCX with Eps8 or calretinin, UBC markers. We also identified DCX-ir elements along the fourth ventricle and its lateral recess that had labeled somata but lacked the dendritic structure characteristic of UBCs. Labeled UBCs were seen in nearby white matter. These results suggest that there may be continued neurogenesis and/or migration of UBCs in the adult. Another possibility is that UBCs maintain DCX expression even after migration and maturation, reflecting a role of DCX in adult neuronal plasticity in addition to a developmental role in migration. PMID:22198017

  10. Ornithine In Vivo Administration Disrupts Redox Homeostasis and Decreases Synaptic Na(+), K (+)-ATPase Activity in Cerebellum of Adolescent Rats: Implications for the Pathogenesis of Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome.

    PubMed

    Zanatta, Ângela; Viegas, Carolina Maso; Hickmann, Fernanda Hermes; de Oliveira Monteiro, Wagner; Sitta, Angela; de Moura Coelho, Daniela; Vargas, Carmen Regla; Leipnitz, Guilhian; Wajner, Moacir

    2015-08-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an inborn error of metabolism caused by a defect in the transport of ornithine (Orn) into mitochondrial matrix leading to accumulation of Orn, homocitrulline (Hcit), and ammonia. Affected patients present a variable clinical symptomatology, frequently associated with cerebellar symptoms whose pathogenesis is poorly known. Although in vitro studies reported induction of oxidative stress by the metabolites accumulating in HHH syndrome, so far no report evaluated the in vivo effects of these compounds on redox homeostasis in cerebellum. Therefore, the present work was carried out to investigate the in vivo effects of intracerebellar administration of Orn and Hcit on antioxidant defenses (reduced glutathione concentrations and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase), lipid oxidation (malondialdehyde concentrations), as well as on the activity of synaptic Na(+), K(+)-ATPase, an enzyme highly vulnerable to free radical attack, in the cerebellum of adolescent rats. Orn significantly increased malondialdehyde levels and the activities of all antioxidant enzymes, and reduced Na(+), K(+)-ATPase activity. In contrast, glutathione concentrations were not changed by Orn treatment. Furthermore, intracerebellar administration of Hcit was not able to alter any of these parameters. The present data show for the first time that Orn provokes in vivo lipid oxidative damage, activation of the enzymatic antioxidant defense system, and reduction of the activity of a crucial enzyme involved in neurotransmission. It is presumed that these pathomechanisms may contribute at least partly to explain the neuropathology of cerebellum abnormalities and the ataxia observed in patients with HHH syndrome.

  11. A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis123

    PubMed Central

    Grigereit, Laura; Pickel, James

    2016-01-01

    Abstract The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID:27257630

  12. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

    PubMed

    Ramos-Moreno, Tania; Galazo, Maria J; Porrero, Cesar; Martínez-Cerdeño, Verónica; Clascá, Francisco

    2006-01-01

    Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.

  13. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    PubMed

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding.

  14. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

    PubMed Central

    Polotow, Tatiana G.; Poppe, Sandra C.; Vardaris, Cristina V.; Ganini, Douglas; Guariroba, Maísa; Mattei, Rita; Hatanaka, Elaine; Martins, Maria F.; Bondan, Eduardo F.; Barros, Marcelo P.

    2015-01-01

    Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions. PMID:26426026

  15. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.

    PubMed

    Polotow, Tatiana G; Poppe, Sandra C; Vardaris, Cristina V; Ganini, Douglas; Guariroba, Maísa; Mattei, Rita; Hatanaka, Elaine; Martins, Maria F; Bondan, Eduardo F; Barros, Marcelo P

    2015-09-28

    Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

  16. Cerebellum and personality traits.

    PubMed

    Petrosini, Laura; Cutuli, Debora; Picerni, Eleonora; Laricchiuta, Daniela

    2015-02-01

    Personality traits are multidimensional traits comprising cognitive, emotional, and behavioral characteristics, and a wide array of cerebral structures mediate individual variability. Differences in personality traits covary with brain morphometry in specific brain regions. A cerebellar role in emotional and affective processing and on personality characteristics has been suggested. In a large sample of healthy subjects of both sexes and differently aged, the macro- and micro-structural variations of the cerebellum were correlated with the scores obtained in the Temperament and Character Inventory (TCI) by Cloninger. Cerebellar volumes were associated positively with Novelty Seeking scores and negatively with Harm Avoidance scores. Given the cerebellar contribution in personality traits and emotional processing, we investigated the cerebellar involvement even in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. Interestingly, the subjects with high alexithymic traits had larger volumes in the bilateral Crus 1. The cerebellar substrate for some personality dimensions extends the relationship between personality and brain areas to a structure up to now thought to be involved mainly in motor and cognitive functions, much less in emotional processes and even less in personality individual differences. The enlarged volumes of Crus 1 in novelty seekers and alexithymics support the tendency to action featuring both personality constructs. In fact, Novelty Seeking and alexithymia are rooted in behavior and inescapably have a strong action component, resulting in stronger responses in the structures more focused on action and embodiment, as the cerebellum is.

  17. The Cerebellum and Migraine

    PubMed Central

    Vincent, Maurice; Hadjikhani, Nouchine

    2013-01-01

    Clinical and pathophysiological evidences connect migraine and the cerebellum. Literature on documented cerebellar abnormalities in migraine, however, is relatively sparse. Cerebellar involvement may be observed in 4 types of migraines: in the widespread migraine with aura (MWA) and migraine without aura (MWoA) forms; in particular subtypes of migraine such as basilar-type migraine (BTM); and in the genetically driven autosomal dominant familial hemiplegic migraine (FHM) forms. Cerebellar dysfunction in migraineurs varies largely in severity, and may be subclinical. Purkinje cells express calcium channels that are related to the pathophysiology of both inherited forms of migraine and primary ataxias, mostly spinal cerebellar ataxia type 6 (SCA-6) and episodic ataxia type 2 (EA-2). Genetically driven ion channels dysfunction leads to hyperexcitability in the brain and cerebellum, possibly facilitating spreading depression waves in both locations. This review focuses on the cerebellar involvement in migraine, the relevant ataxias and their association with this primary headache, and discusses some of the pathophysiological processes putatively underlying these diseases. PMID:17578530

  18. Physiological responses during whole body suspension of adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Fell, R. D.; Musacchia, X. J.

    1987-01-01

    The objective of this study was to characterize responses of adult rats to one and two weeks of whole body suspension. Body weights and food and water intakes were initially reduced during suspension, but, while intake of food and water returned to presuspension levels, body weight remained depressed. Diuresis was evident, but only during week two. Hindlimb muscle responses were differential, with the soleus exhibiting the greatest atrophy and the EDL a relative hypertrophy. These findings suggest that adult rats respond qualitatively in a manner similar to juveniles during suspension.

  19. Hypertension after bilateral kidney irradiation in young and adult rats

    SciTech Connect

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-09-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.

  20. Long-term tracing of the BrdU label-retaining cells in adult rat brain.

    PubMed

    Zhang, Lei; Li, Haihong; Zeng, Shaopeng; Chen, Lu; Fang, Zeman; Huang, Qingjun

    2015-03-30

    Stem cells have been shown to be label-retaining, slow-cycling cells. In the adult mammalian central nervous system, the distribution of the stem cells is inconsistent among previous studies. The purpose of the present study was to determine the distribution of BrdU-LRCs and the cell types of the BrdU-LRCs in rat brain. To label BrdU-LRCs in rat brain, six newborn rats were administered intraperitoneal injections of BrdU 50mg/kg/time twice a day at 2h intervals, over four consecutive days. The BrdU-LRCs were detected by immunohistochemistry, the cell types were examined by double immunofluorescence staining for BrdU/GFAP and BrdU/MAP2, and the percentage of BrdU-LRCs was calculated following a chase period of 24 weeks post-injection. We observed that BrdU-LRCs distributed extensively in rat brain. In the LV, DG, striatum, cerebellum and neocortex, the percentage of BrdU-LRCs was 11.3 ± 2.5%, 10.9 ± 1.3%, 6.4 ± 1.2%, 5.6 ± 0.8%, and 4.9 ± 0.6%, respectively. The highest density of BrdU-LRCs was in LV and DG, the known stem cell sites in adult mammalian brain. Both BrdU/GFAP and BrdU/MAP2 double-staining cells could be detected in the above five brain subregions. Ongoing cell production was widespread in the adult mammalian brain, which would allow us to reevaluate the capacity and potentiality of the brain in homeostasis, wound repair, and regeneration.

  1. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    DTIC Science & Technology

    1991-12-01

    during aggression in rats and some other myomorph species (e.g., Acomys cahirinus, Apcdemus sylvati- cus). Other species (e.g., MusM muau_...which occur when the young are handled. The author reports that, unlike rats, other rodent species (e.g., lab mice, Acomys cahirinus, Clethrionomys gajj... Acomys was removed from the mother’s cage, and during exploratory behavior in Apodemus gyiL vaticus. i1 Sewell, G.D. Ultrasonic signals from rodents

  2. Pattern formation during development of the embryonic cerebellum

    PubMed Central

    Dastjerdi, F. V.; Consalez, G. G.; Hawkes, R.

    2012-01-01

    The patterning of the embryonic cerebellum is vital to establish the elaborate zone and stripe architecture of the adult. This review considers early stages in cerebellar Purkinje cell patterning, from the organization of the ventricular zone to the development of Purkinje cell clusters—the precursors of the adult stripes. PMID:22493569

  3. The cerebellum and cerebellum-like structures of cartilaginous fishes.

    PubMed

    Montgomery, John C; Bodznick, David; Yopak, Kara E

    2012-01-01

    The cerebellum is well developed in cartilaginous fishes, with the same cell types (barring basket cells) and organizational features found in other vertebrate groups, including mammals. In particular, the lattice-like organization of cerebellar cortex (with a molecular layer of parallel fibers, interneurons, spiny Purkinje cell dendrites, and climbing fibers) is a defining characteristic. In addition to the cerebellum, cartilaginous fishes have cerebellum-like structures in the dorsolateral wall of the hindbrain. These structures are adjacent to and, in part, contiguous with the cerebellum. They are cerebellum-like in that they have a molecular layer of parallel fibers and inhibitory interneurons that has striking organizational similarities to the molecular layer of the cerebellar cortex. However, these structures also have characteristics that differ from the cerebellum. For example, cerebellum-like structures do not have climbing fibers and are clearly sensory. They receive direct afferent input from peripheral sensory receptors and relay their outputs to midbrain sensory areas. As a consequence of this close sensory association and the ability of researchers to characterize signal processing in these structures in a behaviorally relevant context, good progress has been made in determining the fundamental processing algorithm of the cerebellum-like structures. This algorithm enables the molecular layer to act as an adaptive filter that cancels self-generated noise in electrosensory and lateral line systems. Given the fundamental similarities of the molecular layer across these structures and the phylogeny of these structures across basal vertebrates, it is clear that these structures share a common genetic-developmental program. Syngeny is a term that has been used to describe similarity of structure due to a shared genetic-developmental program, whether the structures are phylogenetically homologous or not. Given that the cerebellum and cerebellum

  4. Potassium currents in adult rat intracardiac neurones.

    PubMed Central

    Xi-Moy, S X; Dun, N J

    1995-01-01

    1. Properties of K+ currents were studied in isolated adult rat parasympathetic intracardiac neurones with the use of single-electrode voltage-clamp techniques. 2. A hyperpolarization-activated inward rectifier current was revealed when the membrane was clamped close to the resting level (-60 mV). The slowly developing inward relaxation had a mean amplitude of 450 pA at -150 mV, an activation threshold of -60 to -70 mV and a relaxation time constant of 41 ms at -120 mV. The current was reversibly blocked by Cs+ (1 mM) and became smaller with reduced [K+]o and [Na+]o, indicating that this inward rectifier current probably is a time- and voltage-dependent Na(+)-K+ current. 3. Step depolarizations from the holding potential of -80 mV evoked a transient (< 100 ms at -40 mV) outward K+ current (IA) which was blocked by 4-aminopyridine (4-AP, 1 mM). The time constants for IA inactivation were 20 ms at -50 mV and 16 ms at -20 mV. The steady-state activation and (removal of) inactivation curve showed a small overlap between -70 and -40 mV; the reversal potential of IA was close to EK. 4. Step hyperpolarizations from the depolarized potentials, i.e. -30 mV, revealed a slow inward relaxation associated with the deactivation of a time- and voltage-dependent current. The inward relaxation became faster at more hyperpolarized potentials and reversed at -85 and -53 mV in 4.7 and 15 mM [K+]o. This current was blocked by muscarine (20 microM) and Ba2+ (1 mM) but not affected by Cs+ (1 mM); this current may correspond to the M-current (IM). 5. Depolarization-activated outward K+ currents were evoked by holding the membrane close to the resting potential in the presence of tetrodotoxin (TTX, 3 microM), 4-AP (1 mM) and Ba2+ (1 mM). The amplitude of the outward relaxation and the tail current became smaller as the [K+]o was elevated. The outward tail current was reduced in a Ca(2+)-free solution and the residual current was eliminated by the addition of tetraethylammonium (TEA, 10 m

  5. Adrenal and gonadal function in hypothyroid adult male rats.

    PubMed

    Tohei, A; Akai, M; Tomabechi, T; Mamada, M; Taya, K

    1997-01-01

    The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouraciltreated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH.

  6. Resistance Training Alters the Proportion of Skeletal Muscle Fibers but Not Brain Neurotrophic Factors in Young Adult Rats

    PubMed Central

    Antonio-Santos, José; Ferreira, Diórginis José S.; Gomes Costa, Gizelle L.; Matos, Rhowena Jane B.; Toscano, Ana E.; Manhães-de-Castro, Raul

    2016-01-01

    Abstract Antonio-Santos, J, Ferreira, DJS, Gomes Costa, GL, Matos, RJB, Toscano, AE, Manhães-de-Castro, R, and Leandro, CG. Resistance training alters the proportion of skeletal muscle fibers but not brain neurotrophic factors in young adult rats. J Strength Cond Res 30(12): 3531–3538, 2016—Resistance training (RT) is related to improved muscular strength and power output. Different programs of RT for rats have been developed, but peripheral and central response has not been evaluated directly in the same animal. To test the hypothesis that RT induces central and peripheral adaptations, this study evaluated the effects of a RT on the performance of a weekly maximum overload test, fiber-type typology, and brain neurotrophic factors in young adult rats. Thirty-one male Wistar rats (65 ± 5 days) were divided in 2 groups: nontrained (NT, n = 13) and trained (T, n = 18). Trained group was submitted to a program of RT ladder climbing, gradually added mass, 5 days per week during 8 weeks at 80% of individual maximum overload. This test was weekly performed to adjust the individual load throughout the weeks for both groups. After 48 hours from the last session of exercise, soleus and extensor digital longus (EDL) muscles were removed for myofibrillar ATPase staining analysis. Spinal cord, motor cortex, and cerebellum were removed for RT-PCR analysis of BDNF and insulin-like growth factor-1 (IGF-1) gene expression. In EDL muscle, T animals showed an increase in the proportion of type IIb fibers and a reduction of type IIa fibers. Insulin-like growth factor-1 gene expression was reduced in the cerebellum of T animals (NT: 1.025 ± 0.12; T: 0.57 ± 0.11). Our data showed that 8 weeks of RT were enough to increase maximum overload capacity and the proportion of glycolytic muscle fibers, but there were no associations with the expression of growth neurotrophic factors. PMID:27870699

  7. Expression of connexin36 in the adult and developing rat brain.

    PubMed

    Belluardo, N; Mudò, G; Trovato-Salinaro, A; Le Gurun, S; Charollais, A; Serre-Beinier, V; Amato, G; Haefliger, J A; Meda, P; Condorelli, D F

    2000-05-19

    The distribution of connexin36 (Cx36) in the adult rat brain and retina has been analysed at the protein (immunofluorescence) and mRNA (in situ hybridization) level. Cx36 immunoreactivity, consisting primarily of round or elongated puncta, is highly enriched in specific brain regions (inferior olive and the olfactory bulb), in the retina, in the anterior pituitary and in the pineal gland, in agreement with the high levels of Cx36 mRNA in the same regions. A lower density of immunoreactive puncta can be observed in several brain regions, where only scattered subpopulations of cells express Cx36 mRNA. By combining in situ hybridization for Cx36 mRNA with immunohistochemistry for a general neuronal marker (NeuN), we found that neuronal cells are responsible for the expression of Cx36 mRNA in inferior olive, cerebellum, striatum, hippocampus and cerebral cortex. Cx36 mRNA was also demonstrated in parvalbumin-containing GABAergic interneurons of cerebral cortex, striatum, hippocampus and cerebellar cortex. Analysis of developing brain further revealed that Cx36 reaches a peak of expression in the first two weeks of postnatal life, and decreases sharply during the third week. Moreover, in these early stages of postnatal development Cx36 is detectable in neuronal populations that are devoid of Cx36 mRNA at the adult stage. The developmental changes of Cx36 expression suggest a participation of this connexin in the extensive interneuronal coupling which takes place in several regions of the early postnatal brain.

  8. Lycium europaeum fruit extract: antiproliferative activity on A549 human lung carcinoma cells and PC12 rat adrenal medulla cancer cells and assessment of its cytotoxicity on cerebellum granule cells.

    PubMed

    Ghali, Wafa; Vaudry, David; Jouenne, Thierry; Marzouki, Mohamed Nejib

    2015-01-01

    Cancer is a major worldwide health problem and one of the leading causes of death either in developed or developing countries. Plant extracts and derivatives have always been used for various disease treatments and many anticancer agents issued from plants and vegetables are clinically recognized and used all over the world. Lycium europaeum (Solanaceae) also called "wolfberry" was known since ancient times in the Mediterranean area as a medicinal plant and used in several traditional remedies. The Lycium species capacity of reducing the incidence of cancer and also of halting or reserving the growth of cancer was reported by traditional healers. In this study, the antiproliferative capacity, protective properties, and antioxidant activity of the hydro-alcoholic fruit extract of Lycium europaeum were investigated. Results showed that Lycium extract exhibits the ability to reduce cancer cell viability, inhibits proliferation, and induces apoptosis in A549 human lung cancer cells and PC12 rat adrenal medulla cancer cells, in a concentration- and time-dependent manner. Cytotoxic effect on normal rat cerebellum granule cells was assessed to be nonsignificant. Results also showed that Lycium fruit extract protected lipids, proteins, and DNA against oxidative stress damages induced by H2O2 via scavenging reactive oxygen species.

  9. [In vitro organotypic cultivation of adult newt and rat retinas].

    PubMed

    Novikova, Iu P; Aleĭnikova, K S; Krasnov, M S; Poplinskaia, V A; Grigorian, E N

    2010-01-01

    Adult rat and newt retinas were studied during long organotypic 3D cultivation. A high proliferation level was discovered in the region of growth by applying DNA synthesis markers and in vitro mitosis registration in newt retina. Aggregates were formed in the retina spheroid cavity because dedifferentiated cells migrated into this region. Small cell populations in nuclear layers also had dividing and migration capacity. Rosette formation has been shown in newt retina. It is a characteristic of fetal retinal development under pathological conditions. The antiG FAP antibody dye demonstrated an increase in the parent M@uller cell population and generation of a small cell pool with short GFAP-extensions de novo. Recoverin expression studies detected its translocation from photoreceptor extensions to the cell bodies. Moreover, protein was presented in some cells inside the spheroid. It has been shown for the first time that cell proliferation occurred in the developing adult rat retinal spheroid in vitro; BrdU-positive cells and multiple mitoses were revealed in this zone. However, the source of proliferation was not in the peripheral retina, and stable macrophages and glial cells located among neurons of the inner nuclear layer had the ability to divide. The antiGFAP antibody showed an increase in GFAP fibers in the rat retina as well as in the newt retina. Recoverin translocated into photoreceptor perikaryons and the outer plexiform layer in cultivated rat retina. Interestingly, some cells with probably de novo expression of recoverin were discovered in rat and newt retinas.

  10. Consensus Paper: Cerebellum and Emotion.

    PubMed

    Adamaszek, M; D'Agata, F; Ferrucci, R; Habas, C; Keulen, S; Kirkby, K C; Leggio, M; Mariën, P; Molinari, M; Moulton, E; Orsi, L; Van Overwalle, F; Papadelis, C; Priori, A; Sacchetti, B; Schutter, D J; Styliadis, C; Verhoeven, J

    2017-04-01

    Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing.

  11. Endotoxemia in newborn rats attenuates acute pancreatitis at adult age.

    PubMed

    Jaworek, J; Konturek, S J; Macko, M; Kot, M; Szklarczyk, J; Leja-Szpak, A; Nawrot-Porabka, K; Stachura, J; Tomaszewska, R; Siwicki, A; Pawlik, W W

    2007-03-01

    Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar

  12. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  13. [Nitrous compound content in the tissues of the cerebral hemispheres and cerebellum of rats after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Kurkina, L M; Tigranian, R A

    1982-01-01

    The content of ammonia, glutamine, urea, glutamic acid, aspartic acid, and GABA was measured to study nitrogen metabolism. Soon after recovery (6-10 hours after recovery) the content of the above compounds in brain tissues increased, except for GABA whose content decreased. Similar but more marked changes were seen in the brain of control rats exposed to a repeated immobilization stress-effect. These changes were still greater in the flight rats exposed to a repeated immobilization stress-effect postflight. It is suggested that the postflight changes of the above parameters of nitrogen metabolism are induced by stress-agents inherent in space flight and recovery.

  14. Effects of environmental tobacco smoke on adult rat brain biochemistry.

    PubMed

    Fuller, Brian F; Gold, Mark S; Wang, Kevin K W; Ottens, Andrew K

    2010-05-01

    Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of alphaII-spectrin by caspase-3 and the dephosphorylation of serine(116) on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, beta-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

  15. Contextual fear conditioning differs for infant, adolescent, and adult rats

    PubMed Central

    Esmorís-Arranz, Francisco J.; Méndez, Cástor; Spear, Norman E.

    2009-01-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian conditioned suppression. When a discrete auditory conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role. PMID:18343048

  16. Plexin a4 expression in adult rat cranial nerves.

    PubMed

    Gutekunst, Claire-Anne; Gross, Robert E

    2014-11-01

    PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2. PlexinA4 is the latest member of the PlexinA subfamily to be identified. In previous studies, we described the expression of PlexinA4 in the brain and spinal cord of the adult rat. Here, antibodies to PlexinA4 were used to reveal immunolabeling in most of the cranial nerve surveyed. Labeling was found in the olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibulocochlear, glossopharyngeal, vagus, and hypoglossal nerves. This is the first detailed description of the cellular and subcellular distribution of PlexinA4 in the adult cranial nerves. The findings will set the basis for future studies on the potential role of PlexinA4 in regeneration and repair of the adult central and peripheral nervous system.

  17. The effects of a lengthy period of undernutrition from birth and subsequent nutritional rehabilitation on the granule-to-Purkinje cell ratio in the rat cerebellum.

    PubMed Central

    Warren, M A; Bedi, K S

    1988-01-01

    Male rats were undernourished for various lengths of time between birth and 150 days of age, with some rats being nutritionally rehabilitated between 75 and 150 days of age. Eight control and eight experimental rats were anaesthetised and perfused with 2.5% glutaraldehyde at each of 21, 75 and 150 days of age. Stereological procedures were used to estimate granule-to-Purkinje cell ratios in lobes IV, V and VI, using 0.5 micron thick toluidine blue-stained sections. Undernourished rats had significantly lower body and cerebellar weights than controls at all ages examined. These deficits persisted even after a period of nutritional rehabilitation. The granule-to-Purkinje cells ratio did not differ between control and experimental groups at 21 or 75 days of age. However, at 150 days both undernourished and rehabilitated groups of animals had significant deficits in this ratio compared with age-matched controls. These results suggest that undernutrition can have profound effects on brain development in later life even if the effects are not apparent during the period of undernutrition. PMID:3248962

  18. Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

    PubMed

    Lu, Qi; Jiang, Cuiping; Zhang, Jiping

    2016-02-01

    Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time.

  19. Evidence of cellular stress and caspase-3 resulting from a combined two-frequency signal in the cerebrum and cerebellum of Sprague-dawley rats

    PubMed Central

    López-Furelos, Alberto; Leiro-Vidal, José Manuel; Salas-Sánchez, Aarón Ángel; Ares-Pena, Francisco José; López-Martín, María Elena

    2016-01-01

    Multiple simultaneous exposures to electromagnetic signals induced adjustments in mammal nervous systems. In this study, we investigated the non-thermal SAR (Specific Absorption Rate) in the cerebral or cerebellar hemispheres of rats exposed in vivo to combined electromagnetic field (EMF) signals at 900 and 2450 MHz. Forty rats divided into four groups of 10 were individually exposed or not exposed to radiation in a GTEM chamber for one or two hours. After radiation, we used the Chemiluminescent Enzyme-Linked Immunosorbent Assay (ChELISA) technique to measure cellular stress levels, indicated by the presence of heat shock proteins (HSP) 90 and 70, as well as caspase-3-dependent pre-apoptotic activity in left and right cerebral and cerebellar hemispheres of Sprague Dawley rats. Twenty-four hours after exposure to combined or single radiation, significant differences were evident in HSP 90 and 70 but not in caspase 3 levels between the hemispheres of the cerebral cortex at high SAR levels. In the cerebellar hemispheres, groups exposed to a single radiofrequency (RF) and high SAR showed significant differences in HSP 90, 70 and caspase-3 levels compared to control animals. The absorbed energy and/or biological effects of combined signals were not additive, suggesting that multiple signals act on nervous tissue by a different mechanism. PMID:27589837

  20. Prenatal ethanol exposure increases brain cholesterol content in adult rats.

    PubMed

    Barceló-Coblijn, Gwendolyn; Wold, Loren E; Ren, Jun; Murphy, Eric J

    2013-11-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content are known to occur in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43 %, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total polyunsaturated fatty acids (PUFA), in the n-3/n-6 ratio, and in the 22:6n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of postnatal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats.

  1. Hydrocephalus induced via intraventricular kaolin injection in adult rats.

    PubMed

    Shaolin, Z; Zhanxiang, W; Hao, X; Feifei, Z; Caiquan, H; Donghan, C; Jianfeng, B; Feng, L; Shanghang, S

    2015-01-01

    Hydrocephalus is a common neurological disease in humans, but a uniform and particularly effective hydrocephalic animal model amenable to proper appraisal and deep study has not yet been established. In this study, we attempted to construct a high-efficiency model of hydrocephalus via intraventricular kaolin injection. Adult male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 15) and the experimental group (n = 30). Kaolin was injected into the lateral ventricle of experimental animals. Control rats underwent the same procedure but received sterile saline injection instead of kaolin. All animals with kaolin injection into the lateral ventricle developed hydrocephalus according to magnetic resonance imaging (MRI) results (success rate up to 100%). Also, the Morris water maze (MWM) test demonstrated disturbed spatial learning and memory. Furthermore, there were significant differences between groups with respect to the histological changes in the periventricular tissue. Our results indicate that experimental hydrocephalus induced by lateral ventricle injection of kaolin in adult rats is feasible and may be widely used.

  2. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON PROTEIN CARBONYL CONTENT IN FRONTAL CORTEX AND CEREBELLUM OF BROWN NORWAY RATS.

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is poorly understood, largely due to a lack of data on exposures in older adults and adequate animal models. We examined the acute effects of the volatile organic compound, toluene, in a study investigating m...

  3. The Effect of Spaceflight on the Ultrastructure of the Cerebellum

    NASA Technical Reports Server (NTRS)

    Holstein, Gay R.; Martinelli, Giorgio P.

    2003-01-01

    In weightlessness, astronauts and cosmonauts may experience postural illusions as well as motion sickness symptoms known as the space adaptation syndrome. Upon return to Earth, they have irregularities in posture and balance. The adaptation to microgravity and subsequent re-adaptation to Earth occurs over several days. At the cellular level, a process called neuronal plasticity may mediate this adaptation. The term plasticity refers to the flexibility and modifiability in the architecture and functions of the nervous system. In fact, plastic changes are thought to underlie not just behavioral adaptation, but also the more generalized phenomena of learning and memory. The goal of this experiment was to identify some of the structural alterations that occur in the rat brain during the sensory and motor adaptation to microgravity. One brain region where plasticity has been studied extensively is the cerebellar cortex-a structure thought to be critical for motor control, coordination, the timing of movements, and, most relevant to the present experiment, motor learning. Also, there are direct as well as indirect connections between projections from the gravity-sensing otolith organs and several subregions of the cerebellum. We tested the hypothesis that alterations in the ultrastructural (the structure within the cell) architecture of rat cerebellar cortex occur during the early period of adaptation to microgravity, as the cerebellum adapts to the absence of the usual gravitational inputs. The results show ultrastructural evidence for neuronal plasticity in the central nervous system of adult rats after 24 hours of spaceflight. Qualitative studies conducted on tissue from the cerebellar cortex (specifically, the nodulus of the cerebellum) indicate that ultrastructural signs of plasticity are present in the cerebellar zones that receive input from the gravity-sensing organs in the inner ear (the otoliths). These changes are not observed in this region in cagematched

  4. Wnt Expression in the Adult Rat Subventricular Zone After Stroke

    PubMed Central

    Morris, Daniel C.; Zhang, Zheng Geng; Wang, Ying; Zhang, Rui Lan; Greg, Sara; Liu, Xian Shuang; Chopp, Michael

    2007-01-01

    Introduction: In the adult brain, neurogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle. During development, the Wnt pathways contribute to stem cell maintenance and promote neurogenesis. We hypothesized that the Wnt family genes are expressed in neural progenitor cells of the non-ischemic and ischemic SVZ of the adult rodent brain after middle cerebral artery (MCA) occlusion. Methods: Non-ischemic and ischemic cultured SVZ cells and a single population of non-ischemic and ischemic SVZ cells isolated by laser capture microdisection (LCM) were analyzed for Wnt pathway expression using real-time RT-PCR and immunostaining. Results: The number of neurospheres increased significantly (p<0.05) in SVZ cells derived from ischemic (32 ±4.7/rat) compared with the number in non-ischemic SVZ cells (18 ± 3/rat). Wnt family gene mRNA levels were detected in SVZ cells isolated from both cultured and LCM SVZ cells, however there was no upregulation between non-ischemic and ischemic SVZ cells. Immunostaining on brain sections also demonstrated no upregulation of Wnt pathway protein between ischemic and non-ischemic SVZ cells. Conclusions: Expression of the Wnt family genes in SVZ cells suggests that the Wnt pathway may be involved in neurogenesis in the adult brain. However, ischemia does not upregulate Wnt family gene expression. PMID:17400378

  5. Ih without Kir in Adult Rat Retinal Ganglion Cells

    PubMed Central

    Lee, Sherwin C.; Ishida, Andrew T.

    2011-01-01

    Antisera directed against hyperpolarization-activated mixed-cation (“Ih”) and K+ (“Kir”) channels bind to some somata in the ganglion cell layer of rat and rabbit retina. Additionally, the termination of hyperpolarizing current injections can trigger spikes in some cat retinal ganglion cells, suggesting a rebound depolarization due to activation of Ih. However, patch-clamp studies have reported that rat ganglion cells lack inward rectification, or present an inwardly rectifying K+ current. We therefore tested whether hyperpolarization activates Ih in dissociated, adult rat retinal ganglion cell somata. We report here that while we found no inward rectification in some cells, and a Kir-like current in a few cells, hyperpolarization activated Ih in roughly 75% of the cells we recorded from in voltage clamp. We show that this current is blocked by Cs+ or ZD7288 and only slightly reduced by Ba2+, that the current amplitude and reversal potential are sensitive to extracellular Na+ and K+, and that we found no evidence of Kir in cells presenting Ih. In current clamp, injecting hyperpolarizing current induced a slowly relaxing membrane hyperpolarization that rebounded to a few action potentials when the hyperpolarizing current was stopped; both the membrane potential relaxation and rebound spikes were blocked by ZD7288. These results provide the first measurement of Ih in mammalian retinal ganglion cells, and indicate that the ion channels of rat retinal ganglion cells may vary in ways not expected from previous voltage and current recordings. PMID:17488978

  6. Experimental induction of corpora amylacea in adult rat brain.

    PubMed

    Schipper, H M

    1998-10-01

    Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.

  7. Fructose-1,6-bisphosphatase from young and adult rats.

    PubMed

    Klefenz, H F; Rockstein, M

    1976-07-01

    Fructose-1,6-bisphosphatase (E.C. 3.1.3.11) was purified from the livers of young (69-86 days) and adult (370-386 days) Fisher rats. The enzyme preparations were examined for increasing amounts of missynthesized proteins by means of heat-inactivation as well as for differences in regulatory properties. No significant difference with respect to the fraction of rapidly heat-inactivated enzyme or Km- and Ki-values was found. These results do not support the hypothesis that error accumulation resulting in an error catastrophe is a general phenomenon underlying senescence and death.

  8. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  9. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  10. Cerebellum development and medulloblastoma.

    PubMed

    Roussel, Martine F; Hatten, Mary E

    2011-01-01

    In the last 20 years, it has become clear that developmental genes and their regulators, noncoding RNAs including microRNAs and long-noncoding RNAs, within signaling pathways play a critical role in the pathogenesis of cancer. Many of these pathways were first identified in genetic screens in Drosophila and other lower organisms. Mammalian orthologs were subsequently identified and genes within the pathways cloned and found to regulate cell growth. Genes and pathways expressed during embryonic development, including the Notch, Wnt/β-Catenin, TGF-β/BMP, Shh/Patched, and Hippo pathways are mutated, lost, or aberrantly regulated in a wide variety of human cancers, including skin, breast, blood, and brain cancers, including medulloblastoma. These biochemical pathways affect cell fate determination, axis formation, and patterning during development and regulate tissue homeostasis and regeneration in adults. Medulloblastoma, the most common malignant nervous system tumor in childhood, are thought to arise from disruptions in cerebellar development [reviewed by Marino, S. (2005)]. Defining the extracellular cues and intracellular signaling pathways that control cerebellar neurogenesis, especially granule cell progenitor (GCP) proliferation and differentiation has been useful for developing models to unravel the mechanisms underlying medulloblastoma formation and growth. In this chapter, we will review the development of the cerebellar cortex, highlighting signaling pathways of potential relevance to tumorigenesis.

  11. Elephants have relatively the largest cerebellum size of mammals.

    PubMed

    Maseko, Busisiwe C; Spocter, Muhammad A; Haagensen, Mark; Manger, Paul R

    2012-04-01

    The current study used MR imaging to determine the volume of the cerebellum and its component parts in the brain of three adult male African elephants (Loxodonta africana) and compared this with published data from Asian elephants and other mammalian species including odontocete cetaceans, primates, chiropterans, insectivores, carnivores, and artiodactyls. The cerebellum of the adult elephant has a volume of ∼925 mL (average of both African and Asian species). Allometric analysis indicates that the elephant has the largest relative cerebellum size of all mammals studied to date. In addition, both odontocete cetaceans and microchiropterans appear to have large relative cerebellar sizes. The vermal and hemispheric components of the African elephant cerebellum are both large relative to other mammals of similar brain size, however, for odontocete cetaceans the vermal component is small and the hemispheric component is large. These volumetric observations are related to life-histories and anatomies of the species investigated. The current study provides context for one aspect of the elephant brain in the broader picture of mammalian brain evolution.

  12. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  13. Homocysteine Induces Glial Reactivity in Adult Rat Astrocyte Cultures.

    PubMed

    Longoni, Aline; Bellaver, Bruna; Bobermin, Larissa Daniele; Santos, Camila Leite; Nonose, Yasmine; Kolling, Janaina; Dos Santos, Tiago M; de Assis, Adriano M; Quincozes-Santos, André; Wyse, Angela T S

    2017-03-02

    Astrocytes are dynamic glial cells associated to neurotransmitter systems, metabolic functions, antioxidant defense, and inflammatory response, maintaining the brain homeostasis. Elevated concentrations of homocysteine (Hcy) are involved in the pathogenesis of age-related neurodegenerative disorders, such as Parkinson and Alzheimer diseases. In line with this, our hypothesis was that Hcy could promote glial reactivity in a model of cortical primary astrocyte cultures from adult Wistar rats. Thus, cortical astrocytes were incubated with different concentrations of Hcy (10, 30, and 100 μM) during 24 h. After the treatment, we analyzed cell viability, morphological parameters, antioxidant defenses, and inflammatory response. Hcy did not induce any alteration in cell viability; however, it was able to induce cytoskeleton rearrangement. The treatment with Hcy also promoted a significant decrease in the activities of Na(+), K(+) ATPase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as in the glutathione (GSH) content. Additionally, Hcy induced an increase in the pro-inflammatory cytokine release. In an attempt to elucidate the putative mechanisms involved in the Hcy-induced glial reactivity, we measured the nuclear factor kappa B (NFκB) transcriptional activity and heme oxygenase 1 (HO-1) expression, which were activated and inhibited by Hcy, respectively. In summary, our findings provide important evidences that Hcy modulates critical astrocyte parameters from adult rats, which might be associated to the aging process.

  14. Amodiaquine-induced reproductive toxicity in adult male rats.

    PubMed

    Niu, Yan-Ru; Wei, Bing; Chen, Bi; Xu, Li-Hua; Jing, Xia; Peng, Cai-Ling; Ma, Tian-Zhong

    2016-02-01

    Amodiaquine (AQ) is routinely prescribed as an anti-malarial drug. Here, we evaluated AQ-induced toxicity in the male reproductive system. Eighty adult male Sprague-Dawley rats were randomly divided into four groups that received distilled water (control) or daily doses of 5 mg/kg body weight, 10 mg/kg, or 15 mg/kg AQ for 2 weeks. Testes morphology was analyzed using hematoxylin-and-eosin staining, terminal dUTP nicked-end labeling (TUNEL), and immunostaining whereas protein expression was determined by Western blotting. AQ dose-dependently led to abnormal spermatogenesis. Disruption of the blood-testis barrier and increased germ cell apoptosis were observed in all three AQ-treated groups. Interestingly, AQ-induced damage of spermatogenesis recovered over time, based on the survival of promyelocytic leukemia zinc-finger (PLZF)-positive, undifferentiated spermatogonia. Serum levels of luteinizing hormone and testosterone, as well as testicular testosterone levels, were not significantly altered in AQ-treated groups compared with controls. Collectively, our study suggests that AQ exerts substantial acute side effects on the reproductive systems of adult male rats by inducing the apoptosis of differentiating spermatogenic cells and disruption of blood-testis barrier function.

  15. Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis.

    PubMed

    Pinato, Luciana; da Silveira Cruz-Machado, Sanseray; Franco, Daiane G; Campos, Leila M G; Cecon, Erika; Fernandes, Pedro A C M; Bittencourt, Jackson C; Markus, Regina P

    2015-03-01

    Although melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral organs during the mounting of an innate immune response. In the present study, we show that acute neuroinflammation induced by lipopolysaccharide (LPS) injected directly into the lateral ventricles of adult rats reduces the nocturnal peak of melatonin in the plasma and induces its synthesis in the cerebellum, though not in the cortex or hippocampus. This increase in cerebellar melatonin content requires the activation of nuclear factor kappa B (NF-κB), which positively regulates the expression of the key enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT). Interestingly, LPS treatment led to neuronal death in the hippocampus and cortex, but not in the cerebellum. This privileged protection of cerebellar cells was abrogated when G-protein-coupled melatonin receptors were blocked by the melatonin antagonist luzindole, suggesting that the local production of melatonin protects cerebellar neurons from LPS toxicity. This is the first demonstration of a switch between pineal and extra-pineal melatonin production in the central nervous system following a neuroinflammatory response. These results have direct implications concerning the differential susceptibility of specific brain areas to neuronal death.

  16. Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum

    PubMed Central

    Shao, Wei-hua; Chen, Jian-jun; Fan, Song-hua; Lei, Yang; Xu, Hong-bo; Zhou, Jian; Cheng, Peng-fei; Yang, Yong-tao; Rao, Cheng-long; Wu, Bo; Liu, Hai-peng

    2015-01-01

    Abstract Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel “-omics” insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD. PMID:26134254

  17. Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum.

    PubMed

    Shao, Wei-hua; Chen, Jian-jun; Fan, Song-hua; Lei, Yang; Xu, Hong-bo; Zhou, Jian; Cheng, Peng-fei; Yang, Yong-tao; Rao, Cheng-long; Wu, Bo; Liu, Hai-peng; Xie, Peng

    2015-07-01

    Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel "-omics" insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD.

  18. The distribution of stellate cell descending axons in the rat cerebellum: a Golgi and a combined Golgi-electron microscopical study.

    PubMed Central

    Paula-Barbosa, M M; Tavares, M A; Ruela, C; Barroca, H

    1983-01-01

    Axonal descending branches of stellate cells in the molecular layer of the cerebellar cortex of the rat were studied by means of Golgi and combined Golgi-ultrastructural methods. Special attention was paid to those branches from more superficially located cell bodies. With the Golgi method, it was observed that the number of axons from stellate cells forming pericellular baskets and 'pinceaux' increases as their cell bodies come to lie deeper in the layer. With the combined Golgi-ultrastructural method, it was verified that the synaptic contacts established by these axons are identical to those of axons from basket cells, either contacting Purkinje cell bodies or lying around the axon initial segments, where they establish septate-like junctions. This overlapping of axonal territories between stellate and basket cells is in accordance with the hypothesis that these interneurons, although situated at different levels of the cerebellar molecular layer, may be genetically identical cells. Their diversity of form would depend on the cellular microenvironment present at the time of differentiation. Images Figs. 1-4 Figs. 5-7 Fig. 8 Fig. 9 Fig. 10 PMID:6668252

  19. A change in the pattern of activity affects the developmental regression of the Purkinje cell polyinnervation by climbing fibers in the rat cerebellum.

    PubMed

    Andjus, P R; Zhu, L; Cesa, R; Carulli, D; Strata, P

    2003-01-01

    Pattern of activity during development is important for the refinement of the final architecture of the brain. In the cerebellar cortex, the regression from multiple to single climbing fiber innervation of the Purkinje cell occurs during development between postnatal days (P) 5 and 15. However, the regression is hampered by altering in various ways the morpho-functional integrity of the parallel fiber input. In rats we disrupted the normal activity pattern of the climbing fiber, the terminal arbor of the inferior olive neurons, by administering harmaline for 4 days from P9 to P12. At all studied ages (P15-87) after harmaline treatment multiple (double only) climbing fiber EPSC-steps persist in 28% of cells as compared with none in the control. The ratio between the amplitudes of the larger and the smaller climbing fiber-evoked EPSC increases in parallel with the decline of the polyinnervation factor, indicating a gradual enlargement of the synaptic contribution of the winning climbing fiber synapse at the expense of the losing one. Harmaline treatment had no later effects on the climbing fiber EPSC kinetics and I/V relation in Purkinje cells (P15-36). However, there was a rise in the paired-pulse depression indicating a potentiation of the presynaptic mechanisms. In the same period, after harmaline treatment, parallel fiber-Purkinje cell electrophysiology was unaffected. The distribution of parallel fiber synaptic boutons was also not changed. Thus, a change in the pattern of activity during a narrow developmental period may affect climbing fiber-Purkinje cell synapse competition resulting in occurrence of multiple innervation at least up to 3 months of age. Our results extend the current view on the role of the pattern of activity in the refinement of neuronal connections during development. They suggest that many similar results obtained by different gene or receptor manipulations might be simply the consequence of disrupting the pattern of activity.

  20. The neurochemical maturation of the rabbit cerebellum.

    PubMed Central

    Lossi, L; Ghidella, S; Marroni, P; Merighi, A

    1995-01-01

    The immunocytochemical distribution of several neuronal and glial antigens was investigated in the cerebellum of the developing and adult rabbit. Neurofilament positive neurons appeared at embryonic day (E) 25. Purkinje cells transiently expressed neurofilament polypeptides from postnatal day (P) 0 to 15. At later postnatal ages, staining was localised to the parallel fibres, the axonal arbors of the basket cells and fibres of the white matter. Neuron specific enolase (NSE) immunoreactivity was first detected at E25. At P0 Purkinje cells were positive and their staining intensity increased up to P25. From P30 to adulthood virtually all cells in the molecular and Purkinje cell layers were stained. Scattered PGP 9.5-immunoreactive neurons appeared in the cerebellar anlage at P25. Purkinje and Golgi cells were labelled by P0. Synaptophysin immunoreactivity was first observed at P0 in the form of a fine punctate reaction surrounding the perikarya and proximal dendrites of Purkinje cells. By P10, it became particularly intense within the cerebellar glomeruli of the granular layer. Neurons of the deep cerebellar nuclei expressed NSE and PGP 9.5 starting from E25. GFAP and S-100 immunoreactivities were first detected at P10. GFAP-immunopositive astrocytes progressively increased in number up to adulthood. S-100-immunoreactive glial cells were detected throughout the white and grey matter. Bergmann glial cells and their fibres were strongly immunoreactive. Vimentin positive glial cells and fibres were first observed at E15 and persisted up to adulthood. Double labelling experiments using a monoclonal antibody against the proliferating cell nuclear antigen (PCNA), a cyclin synthesised by mitotic cells, showed that neuronal and/or glial polypeptides are expressed only by fully differentiated postmitotic cells. These results indicate that major events in the neurochemical maturation of the rabbit cerebellum occur during the first month after birth, when the same pattern of

  1. Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure

    PubMed Central

    Kantak, Kathleen M.; Barlow, Nicole; Tassin, David H.; Brisotti, Madeline F.; Jordan, Chloe J

    2014-01-01

    Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders). PMID:24800898

  2. The cerebellum and neuropsychiatric disorders.

    PubMed

    Villanueva, Rosa

    2012-08-15

    Relative to non-human primates, in humans the cerebellum, and prefrontal cortex are brain regions which have undergone major evolutionary changes. In recent decades, progress in molecular biology and advances in the development of functional neuroimaging analysis have shown that the evolution of the human cerebellum was accompanied by the acquisition of more functions than were previously deduced from human post-mortem studies and animal experimentation. These new cerebellar functions included the control of attention and other cognitive functions, emotions and mood, and social behavior, which were all thought to represent cortical functions. The importance of this new view of cerebellar physiology has been confirmed by the frequency of neuropsychiatric disorders in individuals with cerebellar abnormalities. The information collected in this review emphasizes the importance of cerebellar studies in establishing the physiological substrate of mental diseases.

  3. Contractile force measured in unskinned isolated adult rat heart fibres.

    PubMed

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  4. Acute toxicity of pesticides in adult and weanling rats.

    PubMed

    Gaines, T B; Linder, R E

    1986-08-01

    LD50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Thirty-six of the chemicals were also tested by the oral route in one sex of weanlings. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and four tested by the dermal route (bufencarb, chlordimeform, dichlofenthion, leptophos) were more toxic to females than to males whereas famphur and 2,4,5-T (oral route) were less toxic to females. Eighteen of the test chemicals were more toxic to the adult than to the weanling and four compounds (leptophos, methidathion, pyrazon, and sulfoxide) were more toxic to the weanling. In additional studies the variability of the LD50 value over a 1-year period was examined for two typical insecticides. Six consecutive bimonthly oral LD50 determinations for parathion and DDT in adults of both sexes indicated that the LD50 values were little affected by the time of year that the tests were done.

  5. Birth insult alters ethanol preference in the adult rat.

    PubMed

    Boksa, P

    1998-05-08

    While genetic factors clearly play a role in regulating ethanol intake, the present study considered the possibility that early environmental factors which influence central nervous system development and long-term function might also alter ethanol intake. The specific aim of the study was to test whether alterations in birth condition, namely Caesarean section (C-section) birth and C-section birth with an added period of global anoxia, can affect subsequent ethanol preference in the adult rat. At 5 months of age, groups of experimental and vaginally born control rats were offered free choice between drinking water or various concentrations of ethanol (1-10% v/v) in water across 36 days of testing. Rats that had been born by C-section with 10 or 15 min of added global anoxia showed significant reductions in ethanol preference scores, in comparison to vaginally born controls. For the 10-min anoxia group, ethanol intake was decreased, water intake was increased and total fluid intake remained unchanged relative to values for vaginally born controls, across the entire test period. Although total fluid intake by the 15-min anoxia group also did not differ from that of vaginally born controls, the decreased ethanol preference scores in the 15-min anoxia group were mainly due to increased water intake during some test periods and a combination of reduced ethanol intake and increased water intake during others. Animals born by rapid C-section alone, with no added period of global anoxia, showed reduced ethanol preference only during a few early periods of testing, a much less pronounced effect than that observed for animals with added global anoxia. When animals were given the choice between drinking water vs. solutions of sucrose or NaCl, no group differences due to birth condition were found on measures of sucrose or NaCl preference. Together with reduced ethanol preference, the 10-min anoxia group showed a transient depression of locomotor activity in response to a low

  6. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  7. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    PubMed

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  8. FACS purification of immunolabeled cell types from adult rat brain.

    PubMed

    Guez-Barber, Danielle; Fanous, Sanya; Harvey, Brandon K; Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G; Picciotto, Marina R; Hope, Bruce T

    2012-01-15

    Molecular analysis of brain tissue is greatly complicated by having many different classes of neurons and glia interspersed throughout the brain. Fluorescence-activated cell sorting (FACS) has been used to purify selected cell types from brain tissue. However, its use has been limited to brain tissue from embryos or transgenic mice with promoter-driven reporter genes. To overcome these limitations, we developed a FACS procedure for dissociating intact cell bodies from adult wild-type rat brains and sorting them using commercially available antibodies against intracellular and extracellular proteins. As an example, we isolated neurons using a NeuN antibody and confirmed their identity using microarray and real time PCR of mRNA from the sorted cells. Our FACS procedure allows rapid, high-throughput, quantitative assays of molecular alterations in identified cell types with widespread applications in neuroscience.

  9. Chordin and noggin expression in the adult rat trigeminal nuclei.

    PubMed

    Hayashi, Yutaro; Mikawa, Sumiko; Masumoto, Kazuma; Katou, Fuminori; Sato, Kohji

    2016-12-01

    Bone morphogenetic proteins (BMP) exert its biological functions by interacting with membrane bound receptors. However, functions of BMPs are also regulated in the extracellular space by secreted antagonistic regulators, such as chordin and noggin. Although the deep involvement of BMP signaling in the development and functions of the trigeminal nuclei has been postulated, little information is available for its expression in the trigeminal nuclei. We, thus, investigated chordin and noggin expression in the adult rat trigeminal nuclei using immunohistochemistry. Chordin and noggin were intensely expressed throughout the trigeminal nuclei. In addition, interesting differences are observed between chordin expression and noggin expression. For example, chordin prefers dendritic expression than noggin, suggesting that chordin is involved in the regulation of dendritic morphology and synaptic homeostasis. Furthermore, chordin and noggin were differentially expressed in the neuropil of the trigeminal nuclei. Since BMP signaling is known to play a pivotal role to make precise neural network, theses differences might be important to keep precise interneuronal connections by regulating local BMP signaling intensity in each region. Interestingly, we also detected chordin and noggin expression in axons of the trigeminal nerves. These data indicate that chordin and noggin play pivotal roles also in the adult trigeminal system.

  10. Transformation of adult rat cardiac myocytes in primary culture.

    PubMed

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  11. Expression of gonadotropin-releasing hormone receptor in cerebral cortical neurons of embryos and adult rats.

    PubMed

    Quintanar, J Luis; Salinas, Eva; González, Rodolfo

    2007-01-03

    Mammalian gonadotropin-releasing hormone (GnRH) was initially isolated from hypothalamus and its receptor from anterior pituitary, although extrapituitary GnRH receptors have been reported. The aim of the present study was to investigate whether GnRH receptor and its mRNA are expressed in cerebral cortical neurons of rat embryos and adult rats using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The immunohistochemistry and RT-PCR analysis showed expression of GnRH receptor and presence of its mRNA, in both cerebral cortical neurons of rat embryos and cerebral cortical tissues of adult rats. Additional experiments showed a decrease in the receptor mRNA expression when cultured neurons of rat embryos were treated with GnRH. It is possible that the presence of GnRH receptors in cortical neurons of rat may be involved in other physiological roles such as neurohormone or neuromodulator.

  12. Enduring and sex-specific effects of adolescent social isolation in rats on adult stress reactivity.

    PubMed

    Weintraub, Ari; Singaravelu, Janani; Bhatnagar, Seema

    2010-07-09

    In adolescence, gender differences in rates of affective disorders emerge. For both adolescent boys and girls, peer relationships are the primary source of life stressors though adolescent girls are more sensitive to such stressors. Social stressors are also powerful stressors for non-human social species like rodents. In a rat model, we examined how social isolation during adolescence impacts stress reactivity and specific neural substrates in adult male and female rats. Rats were isolated during adolescence by single housing from day 30 to 50 of age and control rats were group housed. On day 50, isolated rats and control rats were re-housed in same-treatment same-sex groups. Adult female rats isolated as adolescents exhibited increased adrenal responses to acute and to repeated stress and exhibited increased hypothalamic vasopressin mRNA and BDNF mRNA in the CA3 hippocampal subfield. In contrast, adult male rats isolated as adolescents exhibited a lower corticosterone response to acute stress, exhibited a reduced state of anxiety as assessed in the elevated plus maze and reduced Orexin mRNA compared to adult males group-housed as adolescents. These data point to a markedly different impact of isolation experienced in adolescence on endocrine and behavioral endpoints in males compared to females and identify specific neural substrates that may mediate the long-lasting effects of stress in adolescence.

  13. Solving the mystery of the human cerebellum.

    PubMed

    Leiner, Henrietta C

    2010-09-01

    The mystery of the human cerebellum is this: Why did it enlarge so dramatically in the last million years of human evolution, concomitantly with the greater enlargement of the cerebral cortex? A solution to this mystery was proposed in the 20th century as a result of research by several groups of scientists who investigated the contributions of the cerebellum to the cerebral cortex. In contrast to the 19th century investigations, which were focused on the motor functions of the cerebellum, the focus of the subsequent investigations was expanded to include some mental functions because evidence was produced that the cerebellum contributes to cognition. It was proposed that the combination in the cerebellum of motor and mental capabilities enables the cerebellum to confer on humans some adaptive advantages of great value, and this ability would explain why the human cerebellum has continued to enlarge so dramatically. A valuable adaptive advantage that is included in the proposal is the possibility that the cerebellum couples the motor function of articulating speech to the mental function that selects the language to be spoken, thus helping to produce fluent human speech and language. The validity of this proposal about linguistic processing has not yet been verified. Therefore the mystery of cerebellar enlargement in humans is not yet solved and requires further research.

  14. Juvenile but not adult methamphetamine exposure improves performance in the Morris Water Maze in male rats.

    PubMed

    Moenk, Michael D; Matuszewich, Leslie

    2012-06-01

    Early exposure to psychostimulants has been found to lead to long-lasting effects on cognitive processes. Our lab has previously reported that juvenile male rats administered methamphetamine showed improved performance in a spatial navigation task when tested in adulthood (McFadden and Matuszewich, 2007). What is not known, however, is if these effects are specific to the developing rat, or if a similar methamphetamine protocol given to adult rats would lead to an equally beneficial long-term change in spatial cognition. In the current study, male rats were given 1 daily injection of 2mg/kg methamphetamine or saline for 15 days during either preadolescence (PD20-34) or adulthood (PD70-84). Approximately 45 days after treatment, all rats then underwent 5 days of place training in the Morris water maze at a time when juvenile rats reached adulthood. Similar to previous findings, juvenile rats exposed to repeated methamphetamine displayed shorter latencies and distances to reach the platform throughout training compared to saline-treated rats. The juvenile rats treated with methamphetamine also swam shorter distances and had faster latencies to the hidden platform compared to adult methamphetamine-treated rats. There were no significant differences in rats treated in adulthood with methamphetamine compared to saline-treated rats. Likewise, there were no effects of prior methamphetamine treatment or age on matching-to-place trials or visible platform trials. Overall, the results show that repeated methamphetamine exposure can selectively improve spatial learning in adult male rats when administered during preadolescence, but does not significantly affect spatial learning when administered in adulthood. Furthermore, the current findings demonstrate the unique susceptibility of the developing brain to drugs that modulate dopaminergic activity, as well as the long-term behavioral impact of exposure at critical ages.

  15. Psychophysiological interaction between superior temporal gyrus (STG) and cerebellum: An fMRI study

    NASA Astrophysics Data System (ADS)

    Yusoff, A. N.; Teng, X. L.; Ng, S. B.; Hamid, A. I. A.; Mukari, S. Z. M.

    2016-03-01

    This study aimed to model the psychophysiological interaction (PPI) between the bilateral STG and cerebellum (lobule VI and lobule VII) during an arithmetic addition task. Eighteen young adults participated in this study. They were instructed to solve single-digit addition tasks in quiet and noisy backgrounds during an fMRI scan. Results showed that in both hemispheres, the response in the cerebellum was found to be linearly influenced by the activity in STG (vice-versa) for both in-quiet and in-noise conditions. However, the influence of the cerebellum on STG seemed to be modulated by noise. A two-way PPI model between STG and cerebellum is suggested. The connectivity between the two regions during a simple addition task in a noisy condition is modulated by the participants’ higher attention to perceive.

  16. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    SciTech Connect

    Kodavanti, Prasada Rao S.; Royland, Joyce E.; Richards, Judy E.; Besas, Jonathan; MacPhail, Robert C.

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  17. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats.

    PubMed

    Kodavanti, Prasada Rao S; Royland, Joyce E; Richards, Judy E; Besas, Jonathan; Macphail, Robert C

    2011-11-01

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at -80°C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative

  18. Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats.

    PubMed

    Himes, B T; Liu, Y; Solowska, J M; Snyder, E Y; Fischer, I; Tessler, A

    2001-09-15

    To test the idea that genetically engineered cells can rescue axotomized neurons, we transplanted fibroblasts and immortalized neural stem cells (NSCs) modified to express neurotrophic factors into the injured spinal cord. The neurotrophin-3 (NT-3) or nerve growth factor (NGF) transgene was introduced into these cells using recombinant retroviral vectors containing an internal ribosome entry site (IRES) sequence and the beta-galactosidase or alkaline phosphatase reporter gene. Bioassay confirmed biological activity of the secreted neurotrophic factors. Clarke's nucleus (CN) axons, which project to the rostral spinal cord and cerebellum, were cut unilaterally in adult rats by T8 hemisection. Rats received transplants of fibroblasts or NSCs genetically modified to express NT-3 or NGF and a reporter gene, only a reporter gene, or no transplant. Two months postoperatively, grafted cells survived at the hemisection site. Grafted fibroblasts and NSCs expressed a reporter gene and immunoreactivity for the NGF or NT-3 transgene. Rats receiving no transplant or a transplant expressing only a reporter gene showed a 30% loss of CN neurons in the L1 segment on the lesioned side. NGF-expressing transplants produced partial rescue compared with hemisection alone. There was no significant neuron loss in rats receiving grafts of either fibroblasts or NSCs engineered to express NT-3. We postulate that NT-3 mediates survival of CN neurons through interaction with trkC receptors, which are expressed on CN neurons. These results support the idea that NT-3 contributes to long-term survival of axotomized CN neurons and show that genetically modified cells rescue axotomized neurons as efficiently as fetal CNS transplants.

  19. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin).

    PubMed

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2009-01-01

    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  20. Long-term consequences of neonatal fluoxetine exposure in adult rats.

    PubMed

    Ko, Meng-Ching; Lee, Lukas Jyuhn-Hsiarn; Li, Yang; Lee, Li-Jen

    2014-10-01

    Serotonin (5-HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)-type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late-gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX-exposed adult male rats exhibited reduced locomotor activity and depression-like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX-exposed rats. When the levels of 5-HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long-lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI-type antidepressants during pregnancy should be considered.

  1. Enhanced Behavioral Recovery from Sensorimotor Cortex Lesions After Pyramidotomy in Adult Rats

    PubMed Central

    Fanardjian, V. V.; Gevorkyan, O. V.; Mallina, R. K.; Melik-Moussian, A. B.; Meliksetyan, I. B.

    2000-01-01

    Unilateral transection of the bulbar pyramid, performed before the ablation of the ipsilateral sensorimotor cortex, has been shown to facilitate the recovery of operantly conditioned reflexes and compensatory processes in rats. Such enhanced behaviorai recovery was absent when only the sensorimotor cortex was ablated. This phenomenon is explained by the switching of motor activity under the control of the cortico-rubrospinal system. Switching of the descending influences is accomplished through the following loop: cortico-rubrai projectionred nucleus-inferior olive-cerebellum-thalamuscerebral cortex. This suggests that a preliminary lesion of the peripheral part of the system, represented by a descending spinal projection, facilitates the recovery processes to develop during the subsequent destruction of its central part. PMID:11486486

  2. Neonatal manipulation of oxytocin alters oxytocin levels in the pituitary of adult rats.

    PubMed

    Young, E; Carter, C S; Cushing, B S; Caldwell, J D

    2005-07-01

    The neuropeptide oxytocin (OT) and its OT antagonists (OTA) in infant rats affect their behavior as adults. In this study we attempted to determine whether treating rats on the day of birth (postnatal day 1) with OT or OTA would affect brain OT levels of these rats as adults. Rat pups were injected with OT (3 microg), OTA (0.3 microg) or saline vehicle ip on postnatal day 1. As 60-day-old adults, treated rats were killed, and the OT content in their medial preoptic areas (MPOAs), medial hypothalami (MH) and pituitaries were assayed. In females, treatment with OTA on postnatal day 1 significantly decreased pituitary OT levels as adults. In males, by contrast, treatment with OTA on postnatal day 1 resulted in increased pituitary OT levels when they become adults compared to male rats treated with OT on postnatal day 1. There were no significant effects of neonatal treatment on OT levels in either the MH or MPOA. Day 1 postnatal treatment with OT or OTA had a long-term sexually dimorphic effect on OT levels in the pituitary.

  3. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

    PubMed Central

    Wang, Hua; Lau, Benson Wui-Man; Wang, Ning-li; Wang, Si-ying; Lu, Qing-jun; Chang, Raymond Chuen-Chung; So, Kwok-fai

    2015-01-01

    Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID:26889185

  4. Differential effects of delta9-THC on learning in adolescent and adult rats.

    PubMed

    Cha, Young May; White, Aaron M; Kuhn, Cynthia M; Wilson, Wilkie A; Swartzwelder, H S

    2006-03-01

    Marijuana use remains strikingly high among young users in the U.S., and yet few studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in adolescents compared to adults. This study measured the effects of THC on male adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent (PD=30-32) and adult (PD=65-70) rats were treated acutely with 5.0 mg/kg THC or vehicle while trained on the spatial version of the water maze on five consecutive days. In Experiment 2, adolescent and adult rats were treated acutely with 2.5 or 10.0 mg/kg THC or vehicle while trained on either the spatial and non-spatial versions of the water maze. In Experiment 3, adolescent and adult rats were treated with 5.0 mg/kg THC or vehicle daily for 21 days, and were trained on the spatial and then the non-spatial versions of the water maze task four weeks later in the absence of THC. THC impaired both spatial and nonspatial learning more in adolescents than in adults at all doses tested. However, there were no long-lasting significant effects on either spatial or non-spatial learning in rats that had been previously exposed to THC for 21 days. This developmental sensitivity is analogous to the effects of ethanol, another commonly used recreational drug.

  5. Weanling piglet cerebellum: a surrogate for tolerance to MRT (microbeam radiation therapy) in pediatric neuro-oncology

    NASA Astrophysics Data System (ADS)

    Laissue, Jean A.; Blattmann, Hans; Di Michiel, Marco; Slatkin, Daniel N.; Lyubimova, Nadia; Guzman, Raphael; Zimmermann, Werner; Birrer, Stephan; Bley, Tim; Kircher, Patrick; Stettler, Regina; Fatzer, Rosmarie; Jaggy, Andre; Smilowitz, Henry; Brauer, Elke; Bravin, Alberto; Le Duc, Geraldine; Nemoz, Christian; Renier, Michel; Thomlinson, William C.; Stepanek, Jiri; Wagner, Hans-Peter

    2001-12-01

    The cerebellum of the weanling piglet (Yorkshire) was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss-led program of experimental microbeam radiation therapy (MRT) at the ESRF. Five weanlings in a 47 day old litter of seven, and eight weanlings in a 40 day old litter of eleven were irradiated in November, 1999 and June, 2000, respectively. A 1.5 cm-wide x 1.5 xm-high array of equally space approximately equals 20-30 micrometers wide, upright microbeams spaced at 210 micrometers intervals was propagated horizontally, left to right, through the cerebella of the prone, anesthetized piglets. Skin-entrance intra-microbeam peak adsorbed doses were uniform, either 150, 300, 425, or 600 gray (Gy). Peak and inter-microbeam (valley) absorbed doses in the cerebellum were computed with the PSI version of the Monte Carlo code GEANT and benchmarked using Gafchromic and radiochromic film microdosimetry. For approximately equals 66 weeks [first litter; until euthanasia], or approximately equals 57 weeks [second litter; until July 30, 2001] after irradiation, the littermates were developmentally, behaviorally, neurologically and radiologically normal as observed and tested by experienced farmers and veterinary scientists unaware of which piglets were irradiated or sham-irradiated. Morever, MRT implemented at the ESRF with a similar array of microbeams and a uniform skin-entrance peak dose of 625 Gy, followed by immunoprophylaxis, was shown to be palliative or curative in young adult rats bearing intracerebral gliosarcomas. These observations give further credence to MRT's potential as an adjunct therapy for brain tumors in infancy, when seamless therapeutic irradiation of the brain is hazardous.

  6. Safety of Intracerebroventricular Copper Histidine in Adult Rats

    PubMed Central

    Lem, Kristen E.; Brinster, Lauren R.; Tjurmina, Olga; Lizak, Martin; Lal, Simina; Centeno, Jose A.; Liu, Po-Ching; Godwin, Sarah C.; Kaler, Stephen G.

    2007-01-01

    Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in a P-type ATPase (ATP7A) that normally delivers copper to the developing central nervous system. Infants with large deletions, or other mutations in ATP7A that incapacitate copper transport to the brain, show poor clinical outcomes and subnormal brain copper despite early subcutaneous copper histidine (CuHis) injections. These findings suggest a need for direct central nervous system approaches in such patients. To begin to evaluate an aggressive but potentially useful new strategy for metabolic improvement of this disorder, we studied the acute and chronic effects of CuHis administered by intracerebroventricular (ICV) injection in healthy adult rats. Magnetic resonance imaging (MRI) after ICV CuHis showed diffuse T1-signal enhancement, indicating wide brain distribution of copper after ICV administration, and implying the utility of this paramagnetic metal as a MRI contrast agent. The maximum tolerated dose (MTD) of CuHis, defined as the highest dose that did not induce overt toxicity, growth retardation, or reduce lifespan, was 0.5 mcg. Animals receiving multiple infusions of this MTD showed increased brain copper concentrations, but no significant differences in activity, behavior, and somatic growth, or brain histology compared to saline-injected controls. Based on estimates of the brain copper deficit in Menkes disease patients, CuHis doses 10-fold lower than the MTD found in this study may restore proper brain copper concentration. Our results suggest that ICV CuHis administration have potential as a novel treatment approach in Menkes disease infants with severe mutations. Future trials of direct CNS copper administration in mouse models of Menkes disease will be informative. PMID:17336116

  7. A role for cerebellum in the hereditary dystonia DYT1

    PubMed Central

    Fremont, Rachel; Tewari, Ambika; Angueyra, Chantal; Khodakhah, Kamran

    2017-01-01

    DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA. How these mutations cause dystonia remains unknown. Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients, possibly due to differential developmental compensation between rodents and humans. To address this issue, torsinA was acutely knocked down in select brain regions of adult mice using shRNAs. TorsinA knockdown in the cerebellum, but not in the basal ganglia, was sufficient to induce dystonia. In agreement with a potential developmental compensation for loss of torsinA in rodents, torsinA knockdown in the immature cerebellum failed to produce dystonia. Abnormal motor symptoms in knockdown animals were associated with irregular cerebellar output caused by changes in the intrinsic activity of both Purkinje cells and neurons of the deep cerebellar nuclei. These data identify the cerebellum as the main site of dysfunction in DYT1, and offer new therapeutic targets. DOI: http://dx.doi.org/10.7554/eLife.22775.001 PMID:28198698

  8. Electrophysiological Representation of Scratching CPG Activity in the Cerebellum

    PubMed Central

    Martínez-Silva, Lourdes; Manjarrez, Elias; Gutiérrez-Ospina, Gabriel; Quevedo, Jorge N.

    2014-01-01

    We analyzed the electrical activity of neuronal populations in the cerebellum and the lumbar spinal cord during fictive scratching in adult decerebrate cats before and after selective sections of the Spino-Reticulo Cerebellar Pathway (SRCP) and the Ventral-Spino Cerebellar Tract (VSCT). During fictive scratching, we found a conspicuous sinusoidal electrical activity, called Sinusoidal Cerebellar Potentials (SCPs), in the cerebellar vermis, which exhibited smaller amplitude in the paravermal and hemisphere cortices. There was also a significant spino-cerebellar coherence between these SCPs and the lumbar sinusoidal cord dorsum potentials (SCDPs). However, during spontaneous activity such spino-cerebellar coherence between spontaneous potentials recorded in the same regions decreased. We found that the section of the SRCP and the VSCT did not abolish the amplitude of the SCPs, suggesting that there are additional pathways conveying information from the spinal CPG to the cerebellum. This is the first evidence that the sinusoidal activity associated to the spinal CPG circuitry for scratching has a broad representation in the cerebellum beyond the sensory representation from hindlimbs previously described. Furthermore, the SCPs represent the global electrical activity of the spinal CPG for scratching in the cerebellar cortex. PMID:25350378

  9. Processing past tense in the left cerebellum.

    PubMed

    Mangano, Giuseppa Renata; Turriziani, Patrizia; Bonnì, Sonia; Caltagirone, Carlo; Oliveri, Massimiliano

    2015-01-01

    We report the case of a patient with ischemic lesion of the left cerebellum, who showed specific deficits in processing past versus future tense of action verbs. These findings confirm, in the presence of cerebellar damage, previous results obtained with transcranial magnetic stimulation in healthy subjects and suggest a specificity of the left cerebellum for preparation of responses to the past tense of action verbs. As part of the procedural brain, the cerebellum could play a role in applying the linguistic rules for selection of morphemes typical of past and future tense formation.

  10. Spatiotemporal Expression and Functional Implication of CXCL14 in the Developing Mice Cerebellum

    PubMed Central

    Park, Cho Rong; Kim, Dong-Kyu; Cho, Eun Bee; You, Dong-Joo; do Rego, Jean Luc; Vaudry, David; Sun, Woong; Kim, Hyun; Seong, Jae Young; Hwang, Jong-Ik

    2012-01-01

    Cerebellar granule neurons migrate from the external granule cell layer (EGL) to the internal granule cell layer (IGL) during postnatal morphogenesis. This migration process through 4 different layers is a complex mechanism which is highly regulated by many secreted proteins. Although chemokines are well-known peptides that trigger cell migration, but with the exception of CXCL12, which is responsible for prenatal EGL formation, their functions have not been thoroughly studied in granule cell migration. In the present study, we examined cerebellar CXCL14 expression in neonatal and adult mice. CXCL14 mRNA was expressed at high levels in adult mouse cerebellum, but the protein was not detected. Nevertheless, Western blotting analysis revealed transient expression of CXCL14 in the cerebellum in early postnatal days (P1, P8), prior to the completion of granule cell migration. Looking at the distribution of CXCL14 by immunohistochemistry revealed a strong immune reactivity at the level of the Purkinje cell layer and molecular layer which was absent in the adult cerebellum. In functional assays, CXCL14 stimulated transwell migration of cultured granule cells and enhanced the spreading rate of neurons from EGL microexplants. Taken together, these results revealed the transient expression of CXCL14 by Purkinje cells in the developing cerebellum and demonstrate the ability of the chemokine to stimulate granule cell migration, suggesting that it must be involved in the postnatal maturation of the cerebellum. PMID:22843118

  11. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  12. Nicotine produces long-term increases in cocaine reinforcement in adolescent but not adult rats.

    PubMed

    Reed, Stephanie Collins; Izenwasser, Sari

    2017-01-01

    Studies have shown that many smokers begin using nicotine during adolescence, yet the influence of early nicotine use on the response to other drugs of abuse in adulthood is not fully understood. In the current study, nicotine was administered to adolescent and adult rats for seven days. Thirty days later, cocaine-induced locomotor activity and cocaine self-administration were examined when the rats pretreated as adolescents were adults. Rats exposed to nicotine during early adolescence were sensitized thirty days later to the locomotor-activating effects of cocaine and self-administered a greater number of cocaine infusions than adolescent rats pretreated with vehicle. As a result of this increased intake, the cocaine self-administration dose-response curve was shifted upward indicating an increase in cocaine reinforcement. Rats pretreated with nicotine as adults, however, did not show a difference in locomotor activity or cocaine self-administration thirty days later compared to adult rats pretreated with vehicle. These findings suggest that early exposure to nicotine has long-term consequences on cocaine use. These data further suggest that nicotine use may carry a greater risk during adolescence than adulthood and adolescents who smoke may be particularly vulnerable to stimulant use. This article is part of a Special Issue entitled SI: Adolescent plasticity.

  13. Induction of maternal behavior in adult female rats following chronic morphine exposure during puberty.

    PubMed

    Byrnes, Elizabeth M; Rigero, Beth A; Bridges, Robert S

    2003-12-01

    The peripubertal period in the female rat is the time when the stimulatory effects of opioids on prolactin (PRL) secretion develop. In the adult rat, the administration of chronic high-dose morphine has been shown to attenuate the ability of opiates to stimulate PRL secretion. One function of PRL in adult virgin rats is the induction of maternal behavior. The present study examined whether chronic high-dose morphine exposure during the peripubertal period alters PRL-mediated induction of maternal behavior in adult female rats. Two groups of juvenile female rats were administered increasing doses of morphine or vehicle (s.c.) from age 30 to 50 days. As adults, these females either remained intact, or were ovariectomized and treated with a PRL-dependent, steroid hormone regimen that stimulates a rapid onset of maternal behavior. All females were then exposed daily to rat foster pups to determine whether peripubertal morphine exposure affected their latencies to induce maternal behavior. Morphine treatment resulted in a delay in vaginal opening and a temporary reduction in the rate of weight gain; however, the rate of onset of maternal behavior was unaffected by peripubertal morphine treatment. Thus, chronic morphine exposure in the pubertal female did not impact the expression of pup-induced maternal care.

  14. Acute and adaptive motor responses to caffeine in adolescent and adult rats.

    PubMed

    Rhoads, Dennis E; Huggler, April L; Rhoads, Lucas J

    2011-07-01

    Caffeine is a psychostimulant with intake through foods or beverages tending to increase from childhood through adolescence. The goals of the present study were to examine the effects of caffeine on young adolescent Long-Evans rats and to compare the motor-behavioral responses of adolescent and adult rats to acute and chronic caffeine. Adolescent rats had a biphasic dose-response to caffeine comparable to that reported for adult rats. The magnitude of the motor response to a challenge dose of caffeine (30mg/kg, ip) was similar between adolescent and adult rats. Administration of caffeine in the drinking water (1mg/ml) for a period of 2 weeks led to overall consumption of caffeine which was not significantly different between adolescents and adults when normalized to body mass. There were no impacts of caffeinated drinking water on volume of fluid consumed nor weight gain in either age group compared to age matched controls drinking non-caffeinated tap water. Following this period of caffeine consumption, return to regular drinking water (caffeine withdrawal) led to a significant decrease in baseline movement compared to caffeine-naïve rats. This effect inversion was observed for adolescents but not adults. In addition, the response of the adolescents to the challenge dose of caffeine (30mg/kg, ip) was reduced significantly after chronic caffeine consumption and withdrawal. This apparent tolerance to the caffeine challenge dose was not seen with the adults. Thus, the developing brain of these adolescents may show similar sensitivity to adults in acute caffeine exposure but greater responsiveness to adaptive changes associated with chronic caffeine consumption.

  15. CERES: A new cerebellum lobule segmentation method.

    PubMed

    Romero, Jose E; Coupé, Pierrick; Giraud, Rémi; Ta, Vinh-Thong; Fonov, Vladimir; Park, Min Tae M; Chakravarty, M Mallar; Voineskos, Aristotle N; Manjón, Jose V

    2017-02-15

    The human cerebellum is involved in language, motor tasks and cognitive processes such as attention or emotional processing. Therefore, an automatic and accurate segmentation method is highly desirable to measure and understand the cerebellum role in normal and pathological brain development. In this work, we propose a patch-based multi-atlas segmentation tool called CERES (CEREbellum Segmentation) that is able to automatically parcellate the cerebellum lobules. The proposed method works with standard resolution magnetic resonance T1-weighted images and uses the Optimized PatchMatch algorithm to speed up the patch matching process. The proposed method was compared with related recent state-of-the-art methods showing competitive results in both accuracy (average DICE of 0.7729) and execution time (around 5 minutes).

  16. Dissecting the links between cerebellum and dystonia.

    PubMed

    Malone, Ailish; Manto, Mario; Hass, Chris

    2014-12-01

    Dystonia is a common movement disorder characterized by sustained muscle contractions. These contractions generate twisting and repetitive movements or typical abnormal postures, often exacerbated by voluntary movement. Dystonia can affect almost all the voluntary muscles. For several decades, the discussion on the pathogenesis has been focused on basal ganglia circuits, especially striatal networks. So far, although dystonia has been observed in some forms of ataxia such as dominant ataxias, the link between the cerebellum and dystonia has remained unclear. Recent human studies and experimental data mainly in rodents show that the cerebellum circuitry could also be a key player in the pathogenesis of some forms of dystonia. In particular, studies based on behavioral adaptation paradigm shed light on the links between dystonia and cerebellum. The spectrum of movement disorders in which the cerebellum is implicated is continuously expanding, and manipulation of cerebellar circuits might even emerge as a candidate therapy in the coming years.

  17. Sexual dimorphism and asymmetry in human cerebellum: an MRI-based morphometric study.

    PubMed

    Fan, Lingzhong; Tang, Yuchun; Sun, Bo; Gong, Gaolang; Chen, Zhang J; Lin, Xiangtao; Yu, Taifei; Li, Zhenping; Evans, Alan C; Liu, Shuwei

    2010-09-24

    Structural sexual dimorphism and asymmetry in human cerebellum have been described in previous research, but results remain inconclusive or even conflicting. In this study, gender differences and hemispheric asymmetries in global and regional human cerebellum gray matter (GM) were estimated in an age-matched sample (n=112) of young Chinese adults. An optimized voxel-based morphometry (VBM) in spatial unbiased infratentorial template (SUIT) space together with an automated atlas-based volumetric approach were performed for mapping regional gray matter (GM) gender-related differences across the entire cerebellum. The two methods provided consistent findings on gender differences. The cerebellar GM volume was significantly larger in the anterior and middle posterior lobes of male group. In addition, a trend of greater GM volume in lateral posterior lobe of female group was observed. With the created symmetric cerebellar template, the asymmetric properties of cerebellar hemisphere were also assessed by VBM analysis, showing rightward asymmetry distributed in most cerebellar lobules and leftwards asymmetry distributed in the lobules around the medial posterior lobe. Gender differences in males showed higher leftward asymmetry sparsely within a few lobules and lower rightward asymmetry mainly within lobule Crus II, as compared with females. The acquired detailed morphologic knowledge of normal human cerebellum could establish a baseline for comparison with pathologic changes in the cerebellum. Moreover, our results might help to address controversies in thestudy of sexual dimorphisms and asymmetric patterns in human cerebellum.

  18. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    PubMed Central

    Amrein, Irmgard; Becker, Anton S.; Engler, Stefanie; Huang, Shih-hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K.

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents. PMID

  19. Effects of Neonatal Overfeeding on Juvenile and Adult Feeding and Energy Expenditure in the Rat

    PubMed Central

    Stefanidis, Aneta; Spencer, Sarah J.

    2012-01-01

    Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanim(s) underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL) compared with those from control litters (CL). There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active) phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males) had reduced brown adipose tissue (BAT) temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages. PMID:23251693

  20. Chronic In Vivo Imaging of Ponto-Cerebellar Mossy Fibers Reveals Morphological Stability during Whisker Sensory Manipulation in the Adult Rat123

    PubMed Central

    Rylkova, Daria; Crank, Aidan R.

    2015-01-01

    Abstract The cerebellum receives extensive disynaptic input from the neocortex via the basal pontine nuclei, the neurons of which send mossy fiber (MF) axons to the granule cell layer of the contralateral cerebellar hemisphere. Although this cortico-cerebellar circuit has been implicated in tasks such as sensory discrimination and motor learning, little is known about the potential role of MF morphological plasticity in the function of the cerebellar granule cell layer. To address this issue, we labeled MFs with EGFP via viral infection of the basal pons in adult rats and performed in vivo two-photon imaging of MFs in Crus I/II of the cerebellar hemisphere over a period of several weeks. Following the acquisition of baseline images, animals were housed in control, enriched, or deprived sensory environments. Morphological dynamics were assessed by tracing MF axons and their terminals, and by tracking the stability of filopodia arising from MF terminal rosettes. MF axons and terminals were found to be remarkably stable. Parameters derived neither from measurements of axonal arbor geometry nor from the morphology of individual rosettes and their filopodial extensions significantly changed under control conditions over 4 weeks of imaging. Increasing whisker stimulation by manipulating the sensory environment or decreasing such stimulation by whisker trimming also failed to alter MF structure. Our studies indicate that pontine MF axons projecting to Crus I/II in adult rats do not undergo significant structural rearrangements over the course of weeks, and that this stability is not altered by the sustained manipulation of whisker sensorimotor experience. PMID:26693178

  1. Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats.

    PubMed

    Alaa-Eldin, Eman Ahmad; El-Shafei, Dalia Abdallah; Abouhashem, Nehal S

    2017-01-01

    Commercial mixtures of chlorpyrifos and cypermethrin pesticides are widely used to enhance the toxic effects of cypermethrin on target insects. So, the purpose of the current study was to evaluate the individual and combined toxic effects of chlorpyrifos (CPF) and cypermethrin (CYP) on reproductive system of adult male albino rats. Forty adult male albino rats were randomized into main four groups: group I (control group) included 16 rats, subdivided into negative and positive control; group II (eight rats) received chlorpyrifos 6.75 mg/kg b.w./orally∕daily); group III (eight rats) (received cypermethrin 12.5 mg/kg b.w./orally∕daily); and group IV (eight rats) (received chlorpyrifos and cypermethrin at the same previously mentioned doses). All treatments were given by oral gavage for 12 weeks. We found that single CPF and CYP exposures significantly have adverse effects on reproductive function of adult male albino rats manifested by reduced testicular weight, decreased sperm count, motility and viability, significantly increased percent of morphologically abnormal spermatozoa, and significant increments in sperm DNA fragmentation index (DFI) with respect to control group. Furthermore, serum follicle stimulating hormone, luteinizing hormone, and testosterone levels were decreased significantly compared to control group. This was accompanied with histopathological changes in the testis of rats such as necrosis, degeneration, decreasing number of spermatogenic cells in some seminiferous tubules, edema, congested blood vessels, and exudate in interstitial tissue of the testis. Notably, all these changes were exaggerated in rats treated concomitantly with chlorpyrifos and cypermethrin rendering the mixture more toxic than the additive effects of each compound and causing greater damage on the reproductive system of male albino rats than the individual pesticides.

  2. Embodied cognitive evolution and the cerebellum

    PubMed Central

    Barton, Robert A.

    2012-01-01

    Much attention has focused on the dramatic expansion of the forebrain, particularly the neocortex, as the neural substrate of cognitive evolution. However, though relatively small, the cerebellum contains about four times more neurons than the neocortex. I show that commonly used comparative measures such as neocortex ratio underestimate the contribution of the cerebellum to brain evolution. Once differences in the scaling of connectivity in neocortex and cerebellum are accounted for, a marked and general pattern of correlated evolution of the two structures is apparent. One deviation from this general pattern is a relative expansion of the cerebellum in apes and other extractive foragers. The confluence of these comparative patterns, studies of ape foraging skills and social learning, and recent evidence on the cognitive neuroscience of the cerebellum, suggest an important role for the cerebellum in the evolution of the capacity for planning, execution and understanding of complex behavioural sequences—including tool use and language. There is no clear separation between sensory–motor and cognitive specializations underpinning such skills, undermining the notion of executive control as a distinct process. Instead, I argue that cognitive evolution is most effectively understood as the elaboration of specialized systems for embodied adaptive control. PMID:22734053

  3. Cellular commitment in the developing cerebellum

    PubMed Central

    Marzban, Hassan; Del Bigio, Marc R.; Alizadeh, Javad; Ghavami, Saeid; Zachariah, Robby M.; Rastegar, Mojgan

    2014-01-01

    The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum. PMID:25628535

  4. Ozone Effects on Protein Carbonyl Content in the Frontal Cortex and Cerebellum of Young-Adult, Middle Age, and Senescent Brown Norway Rats

    EPA Science Inventory

    Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is a critical part of community-based human health risk assessment of chemical exposures. There is growing concern over a common air pollutant, ozone ...

  5. Characterization of membrane currents in dissociated adult rat pineal cells.

    PubMed Central

    Aguayo, L G; Weight, F F

    1988-01-01

    1. Membrane currents, particularly the outward components, were studied in pineal cells acutely dissociated from adult rats using the whole-cell variant of the patch-clamp technique. 2. In current clamp, outward constant current elicited a transient graded depolarizing response. A sustained membrane rectification developed within 20 ms; this phenomenon was reduced in cells internally dialysed with 120 mM-CsCl. 3. Study of the membrane current revealed the existence of a transient and a delayed outward current. These currents were virtually eliminated when the cell was internally dialysed with CsCl. 4. The delayed outward current, isolated from a holding potential of -50 mV, activated at potentials near -20 mV, reached a steady-state current amplitude within 60 ms and had little or no decay during steps up to 400 ms in duration. This component was reduced by 80% or more with the addition of 5 mM-TEA. 5. From -100 mV, the transient outward current reached a peak within 15 ms and decayed with a single-exponential time course. The mean decay time constant was 66 +/- 10 ms (at -33 mV) and it showed little voltage sensitivity. This current, which activated at potentials positive to -60 mV and displayed half-inactivation at -76 +/- 8 mV, was reduced by 50% with the addition of 5 mM-4-AP (4-amino-pyridine). 6. In the presence of external Ca2+, the current-voltage relationship for the delayed current did not display a region of negative-slope conductance (N-shape). Increasing the intracellular ionized Ca2+ concentration by varying the Ca-EGTA buffer ratio did not alter the dependence of the current on the membrane potential. 7. Block of outward currents with internal Cs+ revealed a small (less than 90 pA) inward Ca2+ current when the external Ca2+ concentration was increased to 10 mM. From a holding potential of -50 mV, it had a threshold at -30 mV and peaked at +5 mV. Evidence for an inward Na+ current was not obtained. 8. We conclude that acutely dissociated pineal cells

  6. Adaptations of young adult rat cortical bone to 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

    1992-01-01

    To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

  7. Ethanol facilitation of short-term memory in adult rats with a disturbed circadian cycle.

    PubMed

    Mikolajczak, P; Okulicz-Kozaryn, I; Nowaczyk, M; Kaminska, E

    2001-01-01

    The aim of this study was to evaluate the effect of 3-month ethanol treatment on olfactory social memory test performance using two inter-exposure intervals [30 min: short-term recognition (STR); or 120 min: long-term recognition (LTR)] in adult rats with a disturbed circadian cycle (DCC). Ethanol treatment both in ethanol-preferring and -non-preferring groups improved the STR task compared to control rats. However, LTR procedure triggered the opposite tendency. Moreover, no differences between control rats with DCC and those with normal diurnal rhythm in STR and LTR paradigms were observed. Our results suggest that, under some conditions, alcohol facilitates short-term memory in adult rats.

  8. Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

    PubMed

    Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

    2009-12-01

    Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

  9. Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus.

    PubMed

    Bosquiazzo, Verónica L; Vigezzi, Lucía; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2013-11-01

    The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol.

  10. Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

    PubMed Central

    Alvarez, Pedro; Green, Paul G.; Levine, Jon D.

    2013-01-01

    Background Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear. Methods Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding, NLB) for one week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines, interleukin 6 (IL-6) and tumor necrosis alpha (TNFα) in nociception, was evaluated through of behavioral and ELISA assays, surgical interventions and intrathecal antisense treatments. Results Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6-receptor subunit gp130, but not to TNFα type 1 receptor (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared to control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNFα, whereas sound stress increases IL-6 plasma levels in control but not in NLB rats. Conclusions Early-life stress induces a persistent elevation of IL-6, hyperalgesia and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and pro-inflammatory cytokines acting at muscle nociceptor level. PMID:23706525

  11. Intermittent access to beer promotes binge-like drinking in adolescent but not adult Wistar rats.

    PubMed

    Hargreaves, Garth A; Monds, Lauren; Gunasekaran, Nathan; Dawson, Bronwyn; McGregor, Iain S

    2009-06-01

    Teenagers are more likely than adults to engage in binge drinking and could be more vulnerable to long-term brain changes following alcohol abuse. We investigated the possibility of excessive adolescent drinking in a rodent model in which beer (4.44% ethanol vol/vol) is presented to adult and adolescent male Wistar rats. Experiment 1 tracked ad libitum beer and water consumption in group-housed rats from postnatal day (PND) 28-96. Rats consumed an average of 7.8 g/kg/day of ethanol during adolescence (PND 34-55) and this gradually declined to a lower level of intake in adulthood (PND 56-93) of 3.9 g/kg/day. In Experiment 2, beer was made available to both adolescent (PND 29+) and adult (PND 57+) rats for 2h each day in a custom-built "lickometer" apparatus over 75 days. Access to beer was provided either 1 day out of every 3 ("intermittent" groups) or every day ("daily" groups). Relative to body weight, adolescent rats consumed more beer than adult rats in these limited access sessions. Adolescents with intermittent access consumed more than adolescents with daily access, a "binge"-like effect that was not observed in adult groups and that disappeared in adulthood. After 3 months of daily or intermittent alcohol consumption, the preference for beer versus sucrose was assessed. Rats previously kept under an intermittent schedule displayed a higher preference for beer relative to 3% sucrose, but only when testing occurred after 2 days of abstinence. In Experiment 3, adolescent (PND 30-37) and adult (PND 58-65) rats were given 20-min access to beer and their blood alcohol concentrations (BACs) were assessed. Adolescent groups consumed more alcohol than adults and showed higher BACS that were typical of human "binge" drinking (>80 mg/dL). Despite this, the correlation between BAC and beer intake was similar in both age groups. Together these results show that the intermittent presentation of alcohol itself appears to have subtle long-lasting effects on the motivation

  12. Increased rat neonatal activity influences adult cytokine levels and relative muscle mass

    PubMed Central

    Buchowicz, Bryce; Yu, Tiffany; Nance, Dwight M.; Zaldivar, Frank P.; Cooper, Dan M.; Adams, Gregory R.

    2011-01-01

    Little is known about the effect of physical activity in early life on subsequent growth and regulation of inflammation. We previously reported that exposure of muscles in growing rats to IL-6 results in decreased muscle growth apparently due to a state of resistance to growth factors such IGF-I and that running exercise could ameliorate this growth defect. Herein we hypothesized that increased activity, for a brief period during neonatal life, would pattern the adult rat towards a less inflammatory phenotype. Neonatal rats were induced to move about their cage for brief periods from day 5 to day 15 postpartum. Additional groups were undisturbed controls (CON) and handled (HAND). Sub-groups of rats were sampled at 30 and 65 days of age. Relative to CON and HAND, neonatal exercise (EX) results in decreased circulating levels of TNFα, IL-6 and IL-1β in adulthood, primarily in male rats. In addition, adult male EX rats had lower body mass and increased skeletal muscle mass suggesting a leaner phenotype. The results of this study suggest that moderate increases in activity early in life can influence the adult toward a more healthy phenotype with regard to inflammatory mediators and relative muscle mass. PMID:20657345

  13. Early life permethrin insecticide treatment leads to heart damage in adult rats.

    PubMed

    Vadhana, M S Dhivya; Carloni, Manuel; Nasuti, Cinzia; Fedeli, Donatella; Gabbianelli, Rosita

    2011-09-01

    Early life environmental exposure to xenobiotics could represent a critical period for the onset of permanent alterations in the structure and function of different organs. Cardiovascular diseases can be related to various factors including environmental toxicants. The aim of the present study was to evaluate the effect of early life permethrin treatment (1/50 LD(50), from 6th to 21st day of life) on heart of adult rats. Increased DNA damage, decreased heart cell membrane fluidity, increased cholesterol content, protein and lipid oxidation were measured in heart cells from adult rats treated with permethrin during the neonatal period with respect to control rats. Moreover, the same group showed higher levels of cholesterol, IL-1β, IL-2, IFN-γ, rat-Rantes and IL-10 cytokines and decreased albumin content in plasma. Lower cholesterol levels and perturbation in the phospholipid lateral diffusion together with decreased GSH levels and increased GPx activity were measured in heart mitochondria of the treated group. Our findings support the evidence that the neonatal period has a critical role in the development of heart disease in adulthood. We hypothesize that the alterations observed in adult rats could depend on epigenetic changes that occurred during this period which influence gene expression throughout the rat's life, leading to alterations of certain parameters related to cardiac function.

  14. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    PubMed

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  15. Gonadotropin-releasing hormone receptor in spinal cord neurons of embryos and adult rats.

    PubMed

    Quintanar, J Luis; Salinas, Eva; González, Rodolfo

    2009-09-11

    Mammalian gonadotropin-releasing hormone (GnRH) and its receptor have been found in the neuroendocrine reproductive axis. However, they can be localized in other extra-pituitary tissues as well including the central nervous system. The present study reports the expression of GnRH receptor and its mRNA in spinal cord neurons of rat embryos and adult rats, using immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemistry showed that the spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor. The study of GnRH receptor mRNAs revealed that both cultured spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor mRNA. Additional in vitro experiments showed that the expression of GnRH receptor mRNA was less in the spinal cord neurons exposed to GnRH compared to unexposed ones. These results raise the possibility that GnRH may play other roles independently from its participation in reproductive function.

  16. Effect of different doses of Malaysian honey on reproductive parameters in adult male rats.

    PubMed

    Mohamed, M; Sulaiman, S A; Jaafar, H; Sirajudeen, K N S

    2012-05-01

    The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats.

  17. Early treatment with metformin induces resistance against tumor growth in adult rats.

    PubMed

    Trombini, Amanda B; Franco, Claudinéia Cs; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane As; Fabricio, Gabriel S; de Sant'Anna, Juliane R; Castro-Prado, Marialba Aa; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo Cf

    2015-01-01

    It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.

  18. Flow of glucose carbon into cholesterol and phospholipids in various regions of the adult rat brain: enhanced incorporation into hypothalamic phospholipids

    SciTech Connect

    Barkai, A.I.

    1981-01-01

    The contribution of glucose carbon to the biosynthesis of cholesterol and phospholipids in distinct brain regions was studied quantitatively in the adult male rat. Rates of flow of glucose carbon into the lipids in vivo were calculated from two measurements: the curve representing the decrease in plasma /sup 14/C-glucose with time and the specific activity of the cerebral lipid 180 minutes after a rapid intravenous injection of a tracer dose of D-U /sup 14/C-glucose. The following brain regions were studied: cerebral cortex, hypothalamus, medulla, and corpus callosum and cerebellum. The values for carbon flow into phospholipids were significantly higher in the hypothalamus than in the whole brain, whereas small, but insignificant, regional differences were found for carbon flow into cholesterol. The conversion of U-/sup 14/C-glucose to individual phospholipids of both hypothalamus and cerebral cortex was further investigated in vitro in order to establish whether the higher rate of carbon flow into hypothalamic phospholipids resulted from enhanced synthesis of a particular phospholipid. In agreement with the results obtained in vivo, the rate of incorporation of /sup 14/C into total phospholipids was 60% higher in hypothalamic tissue. The results indicate that the higher rate of carbon flow into hypothalamic phospholipids might be attributed to enhanced incorporation of glucose carbon to phosphatidyl-choline and phosphatidyl-ethanolamine following a faster conversion of glucose to glycerol in this brain region.

  19. [Disruption of latent inhibition in adult rats after prepubertal dopamine terminals lesions in the ventral hippocampus].

    PubMed

    Loskutova, L V; Kostiunina, N V; Red'kina, A V

    2010-05-01

    Wistar rats were submitted to bilateral ventral hippocampal injection of 6-hydroxydopamine on 32nd day after birth. Latent inhibition was measured in passive or active avoidance tasks when the rats received 20 and 100 pre-exposures of conditioned stimulus. Prepubertal and adult lesioned rats showed a deficit in the latent inhibition but not in the capacity to avoidance learning in presence of the conditioned stimulus novelty. Possible mechanism of the involvement of hippocampal dopaminergic terminals in attention inhibition to irrelevant information is considered.

  20. Maternal exposure to isobutyl-paraben impairs social recognition in adult female rats.

    PubMed

    Kawaguchi, Maiko; Morohoshi, Kaori; Imai, Hideki; Morita, Masatoshi; Kato, Nobumasa; Himi, Toshiyuki

    2010-01-01

    Isobutyl-paraben (IBP), a widely used preservative, exhibits estrogenic activity. We analyzed the effects of exposure to IBP during gestation and lactation via dam on social recognition behavior in ovariectomized offspring of Sprague-Dawley rats. Offspring were ovariectomized at 7 weeks of age, and were used in a social recognition test at 16 weeks of age. Each offspring was exposed to a novel ovariectomized rat four times and to a second novel rat in a fifth exposure. We counted the investigations by offspring of intruder rats. The IBP-exposed rats showed impaired social behavior compared with controls. These data imply that early exposure to IBP may have an effect on adult social behavior, which is reported to be an autism spectrum disorders in humans.

  1. Neonatal sensory deprivation promotes development of absence seizures in adult rats with genetic predisposition to epilepsy.

    PubMed

    Sitnikova, Evgenia

    2011-03-04

    Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence seizures appear after puberty and they are increased with age. It is known that (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the critical period of development, could enhance excitatory activity in the somatosensory cortex. It is hypothesized that the cortex may become more excitable after neonatal vibrissae removal, and this may precipitate absence seizures in adult rats. We found that whisker trimming during the first postnatal weeks caused more rapid development of EEG seizure activity in adult WAG/Rij rats. Epileptic discharges in the trimmed rats were more numerous (vs control), showed longer duration and often appeared in desynchronized and drowsy EEG. The number of absence-like spindle-shaped EEG events (spike-wave spindles) in the whisker-trimmed rats was higher than in control, especially during the intermediate sleep state. An age-dependent increase of intermediate sleep state was found in the trimmed rats, but not in the intact animals. We discuss epigenetic factors that can modulate absence epilepsy in genetically prone subjects.

  2. The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

    PubMed Central

    Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

    2016-01-01

    Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

  3. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-09-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  4. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system.

  5. Ventilatory phenotypes among four strains of adult rats.

    PubMed

    Hodges, Matthew R; Forster, Hubert V; Papanek, Paula E; Dwinell, Melinda R; Hogan, Genevieve E

    2002-09-01

    Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive (n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O(2)-88% N(2)), hypercapnia (7% CO(2)), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO(2) (P < 0.001), an accentuated ventilatory response to exercise (P < 0.05), and an accentuated ventilatory roll-off during hypoxia (P < 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains (P > 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO(2) sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO(2) sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms.

  6. Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.

    PubMed

    Morris, S A; Kelso, M L; Liput, D J; Marshall, S A; Nixon, K

    2010-02-01

    Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on

  7. Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats.

    PubMed

    Glenn, Melissa J; Adams, Raven S; McClurg, Lauren

    2012-03-14

    Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10-22, on postnatal days (PD) 25-50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats' anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression.

  8. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

    During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and

  9. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

    PubMed Central

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-01-01

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

  10. Postnatal ethanol exposure disrupts signal detection in adult rats.

    PubMed

    Woolfrey, Kevin M; Hunt, Pamela S; Burk, Joshua A

    2005-01-01

    Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the "brain growth spurt" has been associated with significant impairments in attention, learning, and memory. The present experiment assessed whether administration of ethanol during the brain growth spurt in the rat, which occurs shortly after birth, disrupts attentional performance. Rats were administered 5.25 g/kg/day ethanol via intragastric intubation from postnatal days (PD) 4-9, sham-intubation, or no intubation (naïve). Beginning at PD 90, animals were trained to asymptotic performance in a two-lever attention task that required discrimination of brief visual signals from trials with no signal presentation. Finally, manipulations of background noise and inter-trial interval duration were conducted. Early postnatal ethanol administration did not differentially affect acquisition of the attention task. However, after rats were trained to asymptotic performance levels, those previously exposed to ethanol demonstrated a deficit in detection of signals but not of non-signals compared to sham-intubated and naïve rats. The signal detection deficit persisted whenever these animals were re-trained in the standard task, but further task manipulations failed to interact with ethanol pretreatment. The present data support the hypothesis that early postnatal ethanol administration disrupts aspects of attentional processing in the rat.

  11. Ethanol induces second-order aversive conditioning in adolescent and adult rats

    PubMed Central

    Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia; Molina, Juan Carlos; Spear, Norman E.

    2011-01-01

    Alcohol abuse and dependence is considered a developmental disorder with etiological onset during late childhood and adolescence, and understanding age-related differences in ethanol sensitivity is important. Low to moderate ethanol doses (0.5 and 2.0 g/kg, i.g.) induce single-trial, appetitive second-order place conditioning (SOC) in adolescent, but not adult, rats. Recent studies have demonstrated that adolescents may be less sensitive than adults to the aversive properties of ethanol, reflected by conditioned taste aversion. The present study assessed the aversive motivational effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescent and adults, respectively) using SOC. These doses were derived from Experiment 1, which found similar blood and brain ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol, respectively. In Experiment 2, animals received ethanol or vehicle paired with intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or three conditioning trials, rats were presented with the CS1 while in a distinctive chamber (CS2). When tested for CS2 preference, ethanol-treated animals exhibited reduced preference for the CS2 compared with controls. This result, indicative of ethanol-mediated aversive place conditioning, was similar for adolescents and adults, for females and males, and after one, two, or three training trials. One finding, however, suggested that adolescents were less sensitive than adults to ethanol’s aversive effects at the intermediate level of training. In conjunction with previous results, the present study showed that in adolescent rats subjected to SOC, ethanol’s hedonic effects vary from appetitive to aversive as the ethanol dose increases. Adolescent and adult animals appear to perceive the post-ingestive effects of high-dose ethanol as similarly aversive when assessed by SOC. PMID:21187242

  12. Muscle mechanical properties of adult and older rats submitted to exercise after immobilization

    PubMed Central

    Kodama, Fábio Yoshikazu; Camargo, Regina Celi Trindade; Job, Aldo Eloizo; Ozaki, Guilherme Akio Tamura; Koike, Tatiana Emy; Camargo Filho, José Carlos Silva

    2012-01-01

    Objectives To describe the effects of immobilization, free remobilization and remobilization by physical exercise about mechanical properties of skeletal muscle of rats of two age groups. Methods 56 Wistar rats divided into two groups according to age, an adult group (five months) and an older group (15 months). These groups were subdivided in: control, immobilized, free remobilized and remobilized by physical exercise. The pelvic limb of rats was immobilized for seven days. The exercise protocol consisted of five swimming sessions, once per day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile tests, and evaluated the properties: load at the maximum limit, stretching at the maximum limit and stiffness. Results The immobilization reduced the values of load at the maximum limit and the remobilization protocols were not sufficient to restore control levels in adult group and older rats. The stretching at the maximum limit differs only in the older group. Conclusions The immobilization reduces the muscle's ability to bear loads and exercise protocol tends to restore the default at control values in adult and older rats. The age factor only interfered in the stretching at the maximum limit, inducing a reduction of this property in the post-immobilization. Level of Evidence II, Investigating the Results of Treatment. PMID:24453606

  13. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

    PubMed

    Holtz, Nathan A; Carroll, Marilyn E

    2015-06-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

  14. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats

    PubMed Central

    Holtz, Nathan A.; Carroll, Marilyn E.

    2016-01-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability. PMID:25769092

  15. Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

    ERIC Educational Resources Information Center

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

  16. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS. M.N. Logan1, J.R. Thibodeaux2, R.G. Hanson2, C. Lau2. 1North Carolina Central University, Durham, NC, 2Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

    Perfluor...

  17. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  18. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  19. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    PubMed

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  20. Intelligent Network Management and Functional Cerebellum Synthesis

    NASA Technical Reports Server (NTRS)

    Loebner, Egon E.

    1989-01-01

    Transdisciplinary modeling of the cerebellum across histology, physiology, and network engineering provides preliminary results at three organization levels: input/output links to central nervous system networks; links between the six neuron populations in the cerebellum; and computation among the neurons of the populations. Older models probably underestimated the importance and role of climbing fiber input which seems to supply write as well as read signals, not just to Purkinje but also to basket and stellate neurons. The well-known mossy fiber-granule cell-Golgi cell system should also respond to inputs originating from climbing fibers. Corticonuclear microcomplexing might be aided by stellate and basket computation and associate processing. Technological and scientific implications of the proposed cerebellum model are discussed.

  1. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    PubMed

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species.

  2. Electrophysiological properties of newborn and adult rat spinal cord glycine receptors expressed in Xenopus oocytes.

    PubMed Central

    Morales, A; Nguyen, Q T; Miledi, R

    1994-01-01

    The properties of glycine receptors (GlyRs) from newborn and adult rat spinal cord were studied in Xenopus oocytes injected with whole mRNA or the heavy (H) or light (L) mRNA fractions encoding their respective GlyRs. Mean open times and conductances of channels gated by H- or L-GlyRs were determined by noise analysis or voltage jumps. We found that adult H- and L-GlyRs opened channels that differed in their mean open time but had the same channel conductance. Both H- and L-GlyRs gated Cl- currents that displayed a similarly strong outward rectification. Nevertheless, single channels of adult H- and L-GlyRs did not rectify and their mean open times were only slightly altered by voltage. It follows that the outward rectification of adult GlyRs is due mainly to a reduction in the number of open channels. In contrast to H-GlyRs, whose characteristics seem to remain essentially unchanged with age, L-GlyRs from newborn and adult rats have different properties. Channels of newborn L-GlyRs have a higher conductance, longer open time, and greater voltage dependency than those from the adult. Interestingly, properties of newborn GlyRs expressed by whole mRNA were markedly different from those encoded by newborn or adult L or H mRNA. These results demonstrate that the functional heterogeneity of GlyRs is developmentally regulated. PMID:8159710

  3. Autonomic activation associated with ethanol self-administration in adult female P rats.

    PubMed

    Bell, Richard L; Rodd, Zachary A; Toalston, Jamie E; McKinzie, David L; Lumeng, Lawrence; Li, Ting-Kai; McBride, William J; Murphy, James M

    2008-12-01

    The present study examined changes in heart rate (HR) prior to and during limited access ethanol drinking in adult female P rats. P rats were implanted with radio-telemetric transmitters to measure HR. Daily testing involved a 90-min pre-test period (water only available) and a subsequent 90-min test period [either water (W) or ethanol available]. After a week of habituation, one ethanol group had access to ethanol for 7 weeks (CE), and another ethanol group had access for 4 weeks, was deprived for 2 weeks and then had access for a final week (DEP). Analyses of HR revealed that CE and DEP rats had significantly higher HR than W rats during test periods that ethanol was present and that DEP rats displayed higher HR during the early test period of the ethanol deprivation interval, as well. These data indicate that ethanol drinking induces HR activation in adult female P rats, and that this activation can be conditioned to the test cage environment, paralleling reports on contextual conditioning and cue-reactivity in alcoholics exposed to alcohol-associated stimuli. Therefore, this behavioral test may prove advantageous in screening pharmacotherapies for reducing craving and relapse, which are associated with cue-reactivity in abstinent alcoholics.

  4. Bupropion attenuates methamphetamine self-administration in adult male rats.

    PubMed

    Reichel, Carmela M; Murray, Jennifer E; Grant, Kathleen M; Bevins, Rick A

    2009-02-01

    Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg i.p.) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025-0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific.

  5. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  6. Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats

    PubMed Central

    Glenn, Melissa J.; Adams, Raven S.; McClurg, Lauren

    2012-01-01

    Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10–22, on postnatal days (PD) 25–50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats’ anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. PMID:22305146

  7. Multi-Modal Optical Imaging of the Cerebellum in Animals.

    PubMed

    Allegra Mascaro, Anna Letizia; Sacconi, Leonardo; Silvestri, Ludovico; Knott, Graham; Pavone, Francesco S

    2015-10-17

    Thanks to their flexibility, optical techniques could be the key to explore anatomy, plasticity, and functionality of the cerebellum. As an example, an in vivo analysis of the dynamic remodeling of cerebellar axons by nonlinear microscopy can provide fundamental insights of the mechanism that promotes neuronal regeneration. Several studies showed that damaged climbing fibers are capable of regrowing also in adult animals. The investigation of the time-lapse dynamics of degeneration and regeneration of these axons within their complex environment can be performed by time-lapse two-photon fluorescence (TPF) imaging in vivo. Here, we show that single axonal branches can be dissected by laser axotomy, thus avoiding collateral damage to the adjacent dendrite and the formation of a persistent glial scar. Despite the very small denervated area, the injured axons consistently reshaped the connectivity with surrounding neurons and sprouted new branches through the intact surroundings. Correlative light and electron microscopy revealed that the sprouted branch contains large numbers of vesicles, with varicosities in the close vicinity of Purkinje dendrites. By using an RNA interference approach, we found that downregulating GAP-43 causes a significant increase in the turnover of presynaptic boutons and hampers the generation of reactive sprouts. Further, we report how nonlinear microscopy in combination with novel voltage sensitive dyes or transgenic mice allow optical registrations of action potential across a population of neurons opening promising prospective in understanding brain functionality. Finally, we describe novel implementations of light-sheet microscopy to resolve neuronal anatomy in whole cerebellum with cellular resolution. The understanding gained from these complementary optical methods may provide a deeper comprehension of the cerebellum.

  8. Rapid neurobehavioral analysis of Pfiesteria piscicida effects in juvenile and adult rats.

    PubMed

    Levin, E D; Rezvani, A H; Christopher, N C; Glasgow, H B; Deamer-Melia, N J; Burkholder, J M; Moser, V C; Jensen, K

    2000-01-01

    The estuarine dinoflagellate Pfiesteria piscicida is known to kill fish and has been associated with neurocognitive deficits in humans. We have developed a rat model to demonstrate that exposure to Pfiesteria causes significant learning impairments. This has been repeatedly seen as a choice accuracy impairment during radial-arm maze learning. Pfiesteria-induced effects were also seen in a locomotor activity test in the figure-8 apparatus. The current studies used the short-term radial-arm maze acquisition, the figure-8 activity test, and the functional observational battery (FOB) to assess Pfiesteria-induced neurobehavioral effects in adult and juvenile rats. In study 1, the neurobehavioral potency of three different Pfiesteria cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed. Ninety-six (12 per group) adult female Sprague-Dawley rats were injected subcutaneously with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600 or 106,800 Pfiesteria cells per kilogram of rat body weight). One control group (N = 12) was injected with saline and one (N = 12) with aquarium water not containing Pfiesteria. All three of the Pfiesteria samples (p < 0.05) impaired choice accuracy over the first six sessions of training. At the time of the radial-arm maze choice accuracy impairment, no overt Pfiesteria-related effects were seen using an FOB, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the figure-8 apparatus, Pfiesteria treatment caused a significant decrease in mean locomotor activity. In study 2, the neurobehavioral effects of the Pf 728 sample type were assessed in juvenile rats. Twenty-four day-old male and female rats were injected with 35,600 or 106,800 Pf-728 Pfiesteria cells per kilogram of rat body weight. As with adult females, the juvenile rats showed a significant impairment in radial-arm maze choice accuracy. No changes in locomotor activity or the FOB were detected in the

  9. Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats

    PubMed Central

    Liu, Yang; Liang, Zhanhua; Liu, Jing; Zou, Wei; Li, Xiaoyan; Wang, Yachen; An, Lijia

    2013-01-01

    Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged (22–24 month old) rats was significantly lower than that in young (1 month old) and adult (4 months old) rats. pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging. PMID:25206583

  10. Adolescent and adult male rats habituate to repeated isolation, but only adolescents sensitize to partner unfamiliarity.

    PubMed

    Hodges, Travis E; McCormick, Cheryl M

    2015-03-01

    We investigated whether adolescent male rats show less habituation of corticosterone release than adult male rats to acute vs repeated (16) daily one hour episodes of isolation stress, as well as the role of partner familiarity during recovery on social behavior, plasma corticosterone, and Zif268 expression in brain regions. Adolescents spent more time in social contact than did adults during the initial days of the repeated stress procedures, but both adolescents and adults that returned to an unfamiliar peer after isolation had higher social activity than rats returned to a familiar peer (p=0.002) or undisturbed control rats (p<0.001). Both ages showed evidence of habituation, with reduced corticosterone response to repeated than acute isolation (p=0.01). Adolescents, however, showed sensitized corticosterone release to repeated compared with an acute pairing with an unfamiliar peer during recovery (p=0.03), a difference not found in adults. Consistent with habituation of corticosterone release, the repeated isolation groups had lower Zif268 immunoreactive cell counts in the paraventricular nucleus (p<0.001) and in the arcuate nucleus (p=0.002) than did the acute groups, and adolescents had higher Zif268 immunoreactive cell counts in the paraventricular nucleus than did adults during the recovery period (p<0.001), irrespective of stress history and partner familiarity. Partner familiarity had only modest effects on Zif268 immunoreactivity, and experimental effects on plasma testosterone concentrations were only in adults. The results highlight social and endocrine factors that may underlie the greater vulnerability of the adolescent period of development.

  11. Ethanol induces second-order aversive conditioning in adolescent and adult rats.

    PubMed

    Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia; Molina, Juan Carlos; Spear, Norman E

    2011-02-01

    Alcohol abuse and dependence are considered public health problems, with an etiological onset often occurring during late childhood and adolescence, and understanding age-related differences in ethanol sensitivity is important. Low to moderate ethanol doses (0.5 and 2.0 g/kg, intragastrically [i.g.]) induce single-trial, appetitive second-order place conditioning (SOC) in adolescent, but not adult, rats. Recent studies have demonstrated that adolescents may be less sensitive than adults to the aversive properties of ethanol, reflected by conditioned taste aversion. The present study assessed the aversive motivational effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescents and adults, respectively) using SOC. Experiment 1 revealed similar blood and brain ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol, respectively. In Experiment 2, animals received ethanol or vehicle paired with intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or three conditioning trials, the rats were presented with the CS1 while in a distinctive chamber (CS2). When tested for CS2 preference, ethanol-treated animals exhibited reduced preference for the CS2 compared with controls. This result, indicative of ethanol-mediated aversive place conditioning, was similar for adolescents and adults; for females and males; and after one, two, or three training trials. In conjunction with previous results, the present study showed that, in adolescent rats subjected to SOC, ethanol's hedonic effects vary from appetitive to aversive as the ethanol dose increases. Adolescent and adult animals appear to perceive the postingestive effects of high-dose ethanol as similarly aversive when assessed by SOC.

  12. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  13. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    NASA Astrophysics Data System (ADS)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  14. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults.

    PubMed

    Hasegawa, Atsushi; Takahashi, Masahito; Satomi, Kazuhiko; Ohne, Hideaki; Takeuchi, Takumi; Sato, Shunsuke; Ichimura, Shoichi

    2016-01-01

    The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS) and Forelimb Locomotor Scale (FLS) and by measuring the range of motion (ROM) of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2 ± 24.7% in juvenile rats and 34.0 ± 19.8% in adult rats. FLS was 60.4 ± 26.8% in juvenile rats and 46.5 ± 26.9% in adult rats. ROM of the elbow and wrist were 88.9 ± 20.6% and 44.4 ± 24.1% in juvenile rats and 70.0 ± 29.2% and 40.0 ± 21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats.

  15. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

    PubMed Central

    Lensu, Sanna; Ahtiainen, Juha P.; Johansson, Petra P.; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

    2016-01-01

    Key points Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.Our results confirm that sustained aerobic exercise is key in improving AHN. Abstract Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength

  16. Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats

    PubMed Central

    McCall, Nora; Mahadevia, Darshini; Corriveau, Jennifer A.; Glenn, Melissa

    2016-01-01

    The present study explored the effects of supplementing male rats with either choline, omega-3 fatty acids, or phytoestrogens, from weaning into early adulthood, on emotionality and hippocampal plasticity. Because of the neuroprotective properties of these nutrients, we hypothesized that they would positively affect both behavior and hippocampal function when compared to non-supplemented control rats. To test this hypothesis, male Sprague Dawley rats were assigned to one of four nutrient conditions after weaning: 1) control (normal rat chow); 2) choline (supplemented in drinking water); 3) omega 3 fatty acids (daily oral supplements); or 4) phytoestrogens (supplemented in chow). After 4 weeks on their respective diets, a subset of rats began 3 weeks of behavioral testing, while the remaining behaviorally naïve rats were sacrificed after 6 weeks on the diets to assess numbers of adult-born hippocampal neurons using the immature neuron marker, doublecortin. The results revealed that choline supplementation affected emotional functioning; compared to rats in other diet conditions, rats in this group were less anxious in an open field and after exposure to predator odor and showed less behavioral despair after forced swimming. Similar behavioral findings were evident following supplementation with omega-3 fatty acids and phytoestrogens supplementation, though not on all tests and not to the same magnitude. Histological findings followed a pattern consistent with the behavioral findings: choline supplementation, followed by omega-3 fatty acid supplementation, but not phytoestrogen supplementation, significantly increased the numbers of new-born hippocampal neurons. Choline and omega −3 fatty acids have similar biological functions—affecting cell membranes, growth factor levels, and epigenetically altering gene transcription. Thus, the present findings suggest that targeting nutrients with these effects may be a viable strategy to combat adult psychopathologies

  17. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  18. The role of testicular hormones and luteinizing hormone in spatial memory in adult male rats.

    PubMed

    McConnell, Sarah E A; Alla, Juliet; Wheat, Elizabeth; Romeo, Russell D; McEwen, Bruce; Thornton, Janice E

    2012-04-01

    Attempts to determine the influence of testicular hormones on learning and memory in males have yielded contradictory results. The present studies examined whether testicular hormones are important for maximal levels of spatial memory in young adult male rats. To minimize any effect of stress, we used the Object Location Task which is a spatial working memory task that does not involve food or water deprivation or aversive stimuli for motivation. In Experiment 1 sham gonadectomized male rats demonstrated robust spatial memory, but gonadectomized males showed diminished spatial memory. In Experiment 2 subcutaneous testosterone (T) capsules restored spatial memory performance in gonadectomized male rats, while rats with blank capsules demonstrated compromised spatial memory. In Experiment 3, gonadectomized male rats implanted with blank capsules again showed compromised spatial memory, while those with T, dihydrotestosterone (DHT), or estradiol (E) capsules demonstrated robust spatial memory, indicating that T's effects may be mediated by its conversion to E or to DHT. Gonadectomized male rats injected with Antide, a gonadotropin-releasing hormone receptor antagonist which lowers luteinizing hormone levels, also demonstrated spatial memory, comparable to that shown by T-, E-, or DHT-treated males. These data indicate that testicular androgens are important for maximal levels of spatial working memory in male rats, that testosterone may be converted to E and/or DHT to exert its effects, and that some of the effects of these steroid hormones may occur via negative feedback effects on LH.

  19. Effect of morphine, naloxone and histamine system on water intake in adult male rats.

    PubMed

    Eidi, Maryam; Oryan, Shahrbanoo; Eidi, Akram; Sepehrara, Leili

    2003-10-08

    The present study investigated the interaction between histamine and opioid systems on water intake in adult male rats. Intracerebroventricular (i.c.v.) injections were carried out in all experiments. Water intake was measured 1 h after drug injections. Administration of histamine (40-80 microg/rat) and naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat), pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased water intake in isolated rats. Blockade of histamine H1 and H2 receptors attenuated the histamine-induced response. Pyrilamine, but not ranitidine, increased the inhibitory effect induced by morphine. Also, pharmacological blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect on water intake. It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior.

  20. Neuro-oncological disorders of the cerebellum.

    PubMed

    Pfiffner, Thomas J; Jani, Ronak; Mechtler, Laszlo

    2014-11-01

    This article provides an overview of the intra-axial tumors that affect the cerebellum, which can be categorized by location and age. For each tumor, we review conventional neuroimaging findings and discuss the value of more advanced neuroimaging techniques. Current management strategies are also briefly discussed. Finally, cerebellar paraneoplastic disorders and medication-induced cerebellar disorders are discussed.

  1. Dyslexia: The Role of the Cerebellum

    ERIC Educational Resources Information Center

    Fawcett, Angela; Nicolson, Rod

    2004-01-01

    Introduction: In this review article we outline the thinking and evidence behind our hypothesis that the problems suffered by dyslexic people may be attributable to cerebellar deficit. Method: Firstly, we provide an overview of recent evidence that proposes a central role for the cerebellum in cognitive skills, in particular those scaffolded by…

  2. Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats.

    PubMed

    Chin, Vivien S; Van Skike, Candice E; Berry, Raymond B; Kirk, Roger E; Diaz-Granados, Jamie; Matthews, Douglas B

    2011-08-01

    The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA(A) receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.

  3. Beer promotes high levels of alcohol intake in adolescent and adult alcohol-preferring rats.

    PubMed

    Hargreaves, Garth A; Wang, Emyo Y J; Lawrence, Andrew J; McGregor, Iain S

    2011-08-01

    Previous studies suggest that high levels of alcohol consumption can be obtained in laboratory rats by using beer as a test solution. The present study extended these observations to examine the intake of beer and equivalent dilute ethanol solutions with an inbred line of alcohol-preferring P rats. In Experiment 1, male adolescent P rats and age-matched Wistar rats had access to either beer or equivalent ethanol solutions for 1h daily in a custom-built lickometer apparatus. In subsequent experiments, adolescent (Experiment 2) and adult (Experiment 3) male P rats were given continuous 24-h home cage access to beer or dilute ethanol solutions, with concomitant access to lab chow and water. In each experiment, the alcohol content of the beer and dilute ethanol solutions was gradually increased from 0.4, 1.4, 2.4, 3.4, 4.4, 5 to 10% EtOH (vol/vol). All three experiments showed a major augmentation of alcohol intake when rats were given beer compared with equivalent ethanol solutions. In Experiment 1, the overall intake of beer was higher in P rats compared with Wistar rats, but no strain difference was found during the 1-h sessions with plain ethanol consumption. Experiment 1 also showed that an alcohol deprivation effect was more readily obtained in rats with a history of consuming beer rather than plain ethanol solutions. In Experiments 2 and 3, voluntary beer intake in P rats represented ethanol intake of 10-15 g/kg/day, among the highest reported in any study with rats. This excessive consumption was most apparent in adolescent rats. Beer consumption markedly exceeded plain ethanol intake in these experiments except at the highest alcohol concentration (10%) tested. The advantage of using beer rather than dilute ethanol solutions in both selected and nonselected rat strains is therefore confirmed. Our findings encourage the use of beer with alcohol-preferring rats in future research that seeks to obtain high levels of alcohol self-administration.

  4. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  5. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    PubMed

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

  6. Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

    SciTech Connect

    Norton, S.

    1986-04-01

    Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation.

  7. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    PubMed

    MacPhail, R C; Farmer, J D; Jarema, K A

    2012-01-01

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

  8. Chronic nicotine differentially alters cocaine-induced locomotor activity in adolescent vs. adult male and female rats.

    PubMed

    Collins, Stephanie L; Izenwasser, Sari

    2004-03-01

    Tobacco use is prevalent in the adolescent population. It is a major concern because tobacco is highly addictive and has also been linked to illicit drug use. There is not much research, however, on the interaction between nicotine and other stimulant drugs in animal models of early adolescence. This study examined the effects of chronic nicotine alone and on cocaine-stimulated activity in male and female periadolescent rats compared to male and female adult rats. During the seven-day nicotine pretreatment period, nicotine increased locomotor activity in all groups compared to vehicle controls. Male and female adult rats and female periadolescent rats developed sensitization to the locomotor-activating effects of nicotine over the 7-day treatment period, while male periadolescent rats did not. All groups treated with nicotine, however, exhibited sensitization to nicotine-induced repetitive motion over the 7-day nicotine treatment period. On day 8, male periadolescent rats pretreated with nicotine were more markedly sensitized to the locomotor-activating effects of cocaine than male adult rats, while female rats pretreated with nicotine were not sensitized to cocaine. In contrast, male and female periadolescent rats, but not adult rats, had increased amounts of repetitive beam breaks induced by cocaine after nicotine pretreatment. Overall, it appears that cross-sensitization to cocaine is greater in periadolescent than in adult rats, and that males are more sensitized than females. Thus, it may be that nicotine use during adolescence carries a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of cocaine abuse after nicotine use. This information should be taken into account so as to help us better understand the development of drug addiction in adolescents compared to adults.

  9. Effect of amphetamine on adult male and female rats prenatally exposed to methamphetamine.

    PubMed

    Šlamberová, Romana; Macúchová, Eva; Nohejlová, Kateryna; Štofková, Andrea; Jurčovičová, Jana

    2014-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  10. Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Paweł; Wierzba-Bobrowicz, Teresa; Majewska, Maria D

    2010-01-01

    Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism. We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and "dark" neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders.

  11. Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

    PubMed

    Lindquist, Derick H; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E

    2013-09-01

    Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus.

  12. Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats

    PubMed Central

    Joseph, Vincent; Mamet, Julie; Lee, Fuchun; Dalmaz, Yvette; Van Reeth, Olivier

    2002-01-01

    The aim of this study was to test the hypothesis that prenatal hypoxia in rats might lead to consistent changes in the entrainment of the circadian clock by light. Pregnant female rats were placed in a chamber provided with hypoxic gas (10 % O2-90 % N2) at gestational day 5 and returned to normoxia before delivery. Once adult, rats born to hypoxic mothers had significant alterations in their circadian rhythm of locomotor activity (recorded in freely accessible running wheels). Under a regular 12/12 light/dark (LD) cycle, they showed a phase advance of their rhythm of activity (mean phase advance of 87 min) and were less active than control rats. After an abrupt 6 h phase delay in the LD cycle, rats from the prenatal hypoxic group (PNH) took significantly more time to resynchronise to the new LD cycle compared to controls (+53 %; 6.0 ± 1.5 vs. 9.2 ± 0.5 days respectively). Under constant darkness, PNH and control rats had a similar period of activity (24.27 ± 0.20 vs. 24.40 ± 0.13) but the response of PNH rats to a light pulse in the early subjective night was less marked than that of control rats (101 ± 9 vs. 158 ± 13 min). When submitted to acute restraint stress, PNH rats had a prolonged secretion of corticosterone compared to controls. These results indicate that prenatal hypoxia is a factor that has long lasting consequences for the functional output of the biological clock and the hormonal response to stress. PMID:12181309

  13. Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

    PubMed

    Garoui, El Mouldi; Troudi, Afef; Fetoui, Hamadi; Soudani, Nejla; Boudawara, Tahia; Zeghal, Najiba

    2012-11-01

    The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

  14. Noise exposure during early development influences the acoustic startle reflex in adult rats.

    PubMed

    Rybalko, Natalia; Bureš, Zbyněk; Burianová, Jana; Popelář, Jiří; Grécová, Jolana; Syka, Josef

    2011-03-28

    Noise exposure during the critical period of postnatal development in rats results in anomalous processing of acoustic stimuli in the adult auditory system. In the present study, the behavioral consequences of an acute acoustic trauma in the critical period are assessed in adult rats using the acoustic startle reflex (ASR) and prepulse inhibition (PPI) of ASR. Rat pups (strain Long-Evans) were exposed to broad-band noise of 125 dB SPL for 8 min on postnatal day 14; at the age of 3-5 months, ASR and PPI of ASR were examined and compared with those obtained in age-matched controls. In addition, hearing thresholds were measured in all animals by means of auditory brainstem responses. The results show that although the hearing thresholds in both groups of animals were not different, a reduced strength of the startle reflex was observed in exposed rats compared with controls. The efficacy of PPI in exposed and control rats was also markedly different. In contrast to control rats, in which an increase in prepulse intensity was accompanied by a consistent increase in the efficacy of PPI, the PPI function in the exposed animals was characterized by a steep increase in inhibitory efficacy at low prepulse intensities of 20-30 dB SPL. A further increase of prepulse intensity up to 60-70 dB SPL caused only a small and insignificant change of PPI. Our findings demonstrate that brief noise exposure in rat pups results in altered behavioral responses to sounds in adulthood, indicating anomalies in intensity coding and loudness perception.

  15. PROLONGED PERFORMANCE OF A HIGH REPETITION LOW FORCE TASK INDUCES BONE ADAPTATION IN YOUNG ADULT RATS, BUT LOSS IN MATURE RATS

    PubMed Central

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-01-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14–18 mo of age) and 14 young adult (2.5–6.5 mo of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

  16. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty.

    PubMed

    Mendes, Talita Biude; Paccola, Camila Cicconi; de Oliveira Neves, Flávia Macedo; Simas, Joana Noguères; da Costa Vaz, André; Cabral, Regina Elisabeth L; Vendramini, Vanessa; Miraglia, Sandra Maria

    2016-07-01

    The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood.

  17. Developmental analysis of GFAP immunoreactivity in the cerebellum of the meander tail mutant mouse.

    PubMed

    Grishkat, H L; Schwartz, E; Jain, G; Eisenman, L M

    1996-08-01

    It is thought that Bergmann glial fibers assist in the inward migration of granule cells. Model systems in which there is a perturbation of either the migrating cells or the glial cell population have been useful in understanding the migratory process. In the meander tail mutant mouse, the anterior cerebellar region is agranular, whereas the posterior cerebellum is relatively unaffected by the mutation. This study presents a qualitative analysis of the development of cerebellar radial glia in mea/mea and +/mea mice aged from postnatal day 0 to adult, using an antibody against the glia specific antigen, glial fibrillary acidic protein. The results indicate a slight delay in the onset of immunoreactivity in the mea/mea cerebellum and abnormal glial formation in the anterior and posterior regions by postnatal day 5. At postnatal day 11, the full complement of labeled fibers appears to be present and although they appear abnormal in formation, they eventually reach the surface and terminate in oddly shaped and irregularly spaced endfeet. In adult mea/mea and +/mea mice, as compared to the early postnatal stages, there is a significant reduction in GFAP immunoreactive fibers. Cresyl violet stained adult mea/mea sections revealed the presence of ectopic granule cells in radial columns and small clumps at the surface of and within the molecular layer of the caudal cerebellum. Quantitative analyses revealed a 4- to 5-fold increase in the number of ectopic granule cells in lobule VIII of the mea/mea when compared with the +/mea cerebellum. These results suggest that the radial glia in the mea/mea cerebellum exhibit some uncharacteristic morphologies, but that these abnormalities are most likely the consequence of environmental alterations produced by the mutant gene.

  18. Social and non-social anxiety in adolescent and adult rats after repeated restraint.

    PubMed

    Doremus-Fitzwater, Tamara L; Varlinskaya, Elena I; Spear, Linda P

    2009-06-22

    Adolescence is associated with potentially stressful challenges, and adolescents may differ from adults in their stress responsivity. To investigate possible age-related differences in stress responsiveness, the consequences of repeated restraint stress (90 min/day for 5 days) on anxiety, as indexed using the elevated plus-maze (EPM) and modified social interaction (SI) tests, were assessed in adolescent and adult Sprague-Dawley male and female rats. Control groups at each age included non-stressed and socially deprived animals, with plasma corticosterone (CORT) levels also measured in another group of rats on days 1 and 5 of stress (sampled 0, 30, 60, 90, and 120 min following restraint onset). While repeatedly restrained animals exhibited similar anxiety levels compared to non-stressed controls in the EPM, restraint stress increased anxiety at both ages in the SI test (as indexed by reduced social investigation and social preference). Daily weight gain measurements, however, revealed more marked stress-related suppression of body weight in adolescents versus adults. Analysis of stress-induced increases in CORT likewise showed that adolescents demonstrated less habituation than adults, embedded within typical sex differences in CORT magnitude (females greater than males) and age differences in CORT recovery (adolescents slower than adults). Despite no observable age-related differences in the behavioral response to restraint, adolescents were more sensitive to the repeated stressor in terms of physiological indices of attenuated weight gain and habituation of stress-induced CORT.

  19. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    SciTech Connect

    Gorban', E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  20. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    PubMed

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  1. Oligodendroglial maldevelopment in the cerebellum after postnatal hyperoxia and its prevention by minocycline

    PubMed Central

    Scheuer, Till; Brockmöller, Vivien; Knowlton, Marissa Blanco; Weitkamp, Jörn-Hendrik; Ruhwedel, Torben; Mueller, Susanne; Endesfelder, Stefanie; Bührer, Christoph; Schmitz, Thomas

    2015-01-01

    According to recent research, brain injury after premature birth often includes impaired growth of the cerebellum. However, causes of cerebellar injury in this population are poorly understood. In this study, we analyzed whether postnatal hyperoxia perturbs white matter development of the cerebellum, and whether cerebellar glial damage can be prevented by minocycline. We used a hyperoxia model in neonatal rats providing 24h exposure to 4-fold increased oxygen concentration (80% O2) from P6 to P7, followed by recovery in room air until P9, P11, P15, P30. Injections with minocycline were performed at the beginning and 12h into hyperoxia exposure. Hyperoxia induced oxidative stress in the cerebellum at P7 as evidenced by increased nitrotyrosine concentrations. Numbers of proliferating, NG2+Ki67+ oligodendroglial precursor cells were decreased at P7 after hyperoxia and at P11 following recovery in room air. Numbers of mature, CC1+ oligodendrocytes were diminished in recovering hyperoxia rats, and MBP expression was still decreased at P30. Electron microscopy analysis of myelinated fibers at P30 revealed thinner myelin sheath after hyperoxia. Long-term injury of the cerebellum by neonatal hyperoxia was confirmed by reduced volumes in MRI measurements at P30. In response to 80% O2, expression of PDGF-A was largely reduced in cerebellar tissue and also in cultured cerebellar astrocytes. Treatment with minocycline during hyperoxia prevented oxidative stress, attenuated oligodendroglial injury, and improved astroglial PDGF-A levels. In conclusion, early hyperoxia causes white matter damage in the cerebellum with astroglial dysfunction being involved, and both can be prevented by treatment with minocycline. PMID:25964099

  2. Perfluorooctane sulfonate effects on the reproductive axis in adult male rats.

    PubMed

    López-Doval, S; Salgado, R; Pereiro, N; Moyano, R; Lafuente, A

    2014-10-01

    Perfluorooctane sulfonate (PFOS) is a neurotoxic agent and it can disrupt the endocrine system activity. This work was undertaken to evaluate the possible effects of PFOS exposure on the hypothalamic-pituitary-testicular axis (HPT) in adult male rats, and to evaluate the possible morphological alterations induced by PFOS in the endocrine tissues of this axis. Adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, hypothalamic noradrenaline concentration increased in the anterior hypothalamus and in the median eminence, not changing in the mediobasal hypothalamus. PFOS treated rats presented a decrease of the gonadotropin releasing hormone (GnRH) gene expression, increasing the mRNA levels of the luteinizing hormone (LH) in rats treated with all doses administered except with the dose of 6 mg/kg/day. PFOS also induced a raise of the follicle stimulating hormone (FSH) gene expression in the animals exposed to 0.5 and 1.0 mg of PFOS/kg/day. After PFOS exposure, hypothalamic GnRH concentration was modified, LH and testosterone release was inhibited and FSH secretion was stimulated. Moreover, PFOS induced several histopathological alterations in the hypothalamus, pituitary gland and testis. The results obtained in the present study suggest in general terms that PFOS can inhibit the physiological activity of the reproductive axis in adult male rats, which could be explained, at least in part, by the structural alterations showed in the animals exposed to this chemical: very dense chromatin, condensed ribosomes and a loss of the morphology in the hypothalamus; a degeneration of the gonadotrophic cells, as well as a loss and degeneration of the spermatozoids and a very marked edema in the testis.

  3. Airborne particles of the california central valley alter the lungs of healthy adult rats.

    PubMed Central

    Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

    2003-01-01

    Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

  4. Different forms of oestrogen rapidly upregulate cell proliferation in the dentate gyrus of adult female rats.

    PubMed

    Barha, C K; Lieblich, S E; Galea, L A M

    2009-03-01

    Oestrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. The dentate gyrus of the hippocampus retains the ability to produce neurones throughout adulthood and 17beta-oestradiol has been shown to influence hippocampal neurogenesis in adult female rats. The effects of other oestrogens, such as oestrone and 17alpha-oestradiol, on neurogenesis have not been investigated. The present study aimed to investigate the effects of 17beta-oestradiol, oestradiol benzoate, oestrone, and 17alpha-oestradiol on cell proliferation in ovariectomised adult female rats at two different time points. Young ovariectomised female rats were injected with one of the oestrogens at one of three doses. In Experiment 1, rats were exposed to the hormone for 4 h and, in Experiment 2, rats were exposed to the hormone for 30 min prior to 5-bromo-2-deoxyuridine injection to label proliferating cells and their progeny. We found that young ovariectomised females responded with increased cell proliferation to most oestrogens, except oestradiol benzoate, after 30 min of exposure. However, administration of oestrogens for a longer time interval was ineffective at increasing cell proliferation. After 30 min, 17beta-oestradiol and oestrone increased cell proliferation at low (0.3 microg) and high (10 microg) doses, whereas 17alpha-oestradiol increased cell proliferation at medium (1 microg) and high doses. The results of the present study indicate that different oestrogens rapidly increase cell proliferation in a dose-dependent manner, possibly through a nonclassical, nongenomic mechanism. Future experiments should focus on further elucidating the specific pathways utilised by each oestrogen. These results have important therapeutic implications because it may be possible to use 17alpha-oestradiol and lower doses of oestrogens in hormone replacement therapies.

  5. Neuroanatomical distribution of galectin-3 in the adult rat brain.

    PubMed

    Yoo, Hong-Il; Kim, Eu-Gene; Lee, Eun-Jin; Hong, Sung-Young; Yoon, Chi-Sun; Hong, Min-Ju; Park, Sang-Jin; Woo, Ran-Sook; Baik, Tai-Kyoung; Song, Dae-Yong

    2017-04-01

    Galectin-3 is a member of the lectin subfamily that enables the specific binding of β-galactosides. It is expressed in a broad spectrum of species and organs, and is known to have various functions related to cell adhesion, signal transduction, and proinflammatory responses. Although, expression of galectin-3 in some activated neuroglia under neuroinflammation has been well documented in the central nervous system, little is known about the neuronal expression and distribution of galectin-3 in normal brain. To describe the cellular and neuroanatomical expression map of galectin-3, we performed galectin-3 immunohistochemistry on the entire normal rat brain and subsequently analyzed the neuronal distribution. Galectin-3 expression was observed not only in some neuroglia but also in neurons. Neuronal expression of galectin-3 was observed in many functional parts of the cerebral cortex and various other subcortical nuclei in the hypothalamus and brainstem. Neuroanatomical analysis revealed that robust galectin-3 immuno-signals were present in many hypothalamic nuclei related to a variety of physiological functions responsible for mediating anxiety responses, energy balance, and neuroendocrine regulation. In addition, the regions highly connected with these hypothalamic nuclei also showed intense galectin-3 expression. Moreover, multiple key regions involved in regulating autonomic functions exhibited high levels of galectin-3 expression. In contrast, the subcortical nuclei responsible for the control of voluntary motor functions and limbic system exhibited no galectin-3 immunoreactivity. These observations suggest that galectin-3 expression in the rat brain seems to be regulated by developmental cascades, and that functionally and neuroanatomically related brain nuclei constitutively express galectin-3 in adulthood.

  6. Neurones in the adult rat anterior medullary velum.

    PubMed

    Ibrahim, M; Menoud, P A; Celio, M R

    2000-03-27

    The presence of neurones in the rat anterior medullary velum (AMV) has been investigated by using antibodies to the calcium-binding proteins, parvalbumin (PV), calretinin (CR), and calbindin-D28k (CB). Disparate populations of mainly GABAergic neurones were located in the rostral and caudal regions of the AMV. The rostral region of the AMV was characterised by GABAergic CR-labelled or PV-labelled neurones. CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network. PV-labelled neurones had round somata (diameters between 6 and 10 microm) and were bi-tufted, with beaded dendrites. Both CR-labelled and PV-labelled dendrites formed punctate pericellular associations with unlabelled somatic profiles. In the caudal region of the AMV, PV-labelled neurones were GABAergic, multipolar cells, having round somata (diameters between 9 and 12 microm), with either beaded or nonbeaded dendrites forming a network of interconnecting dendrites. PV-labelled pericellular associations were made around both PV-labelled and unlabelled somatic profiles. CR labelled unipolar brush cells (UBCs) were not GABAergic. UBCs were characterised by a round to oval somata (10-15 microm in diameter) from which a single primary dendrite emerged to form a distal expansion having small terminal dendrites. From the distal expansion, there also appeared to be CR-labelled processes emanating and extending for up to 250 microm. CB occasionally labelled "Purkinje-like cells" (PLCs). The rat AMV is a more complex structure than first envisaged with the presence of predominantly inhibitory neurones expressing different calcium-binding proteins. Functional and anatomic aspects of this circuitry are further discussed.

  7. The Intracellular Signaling Molecule Darpp-32 Is a Marker for Principal Neurons in the Cerebellum and Cerebellum-Like Circuits of Zebrafish

    PubMed Central

    Robra, Lena; Thirumalai, Vatsala

    2016-01-01

    The dopamine and cAMP regulated phosphoprotein of apparent molecular weight 32 kDa (Darpp-32) is an inhibitory subunit of protein phosphatase-1 (PP-1). Darpp-32 activity is regulated by multiple ligand-activated G-protein coupled receptors (GPCRs). This protein is coded for by the protein phosphatase-1 regulatory subunit 1b (ppp1r1b) gene. Here, we provide experimental evidence for the presence of multiple isoforms of ppp1r1b in zebrafish. We show that these isoforms are differentially expressed during development with the full-length isoform being maternally deposited. Next, with a custom polyclonal antibody generated against the full-length protein, we show that in the adult, Darpp-32 is strongly expressed in principal neurons of the cerebellum and cerebellum-like circuits. These include Purkinje neurons in the cerebellum, Type-I neurons in the optic tectum, and crest cells in the medial octavolateralis nucleus (MON). We confirmed the identity of these neurons through their colocalization with Parvalbumin 7 immunoreactivity. Darpp-32 is seen in the somata and dendrites of these neurons with faint staining in the axons. In all of these regions, Darpp-32-immunoreactive cells were in close proximity to tyrosine hydroxylase (TH) immunoreactive puncta indicating the presence of direct catecholaminergic input to these neurons. Darpp-32 immunoreactivity was seen in Purkinje neurons as early as 3 days post-fertilization (dpf) when Purkinje neurons are first specified. In sum, we show that Darpp-32, a signaling integrator, is a specific marker of principal neurons in the cerebellum and cerebellum-like circuits in zebrafish. PMID:27540357

  8. Use of the light/dark test for anxiety in adult and adolescent male rats.

    PubMed

    Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

    2013-11-01

    The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.

  9. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    NASA Astrophysics Data System (ADS)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  10. Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.

    PubMed

    Guasti, Leonardo; Paul, Alex; Laufer, Ed; King, Peter

    2011-04-10

    Sonic hedgehog signaling was recently demonstrated to play an important role in murine adrenal cortex development. The organization of the rat adrenal differs from that of the mouse, with the zona glomerulosa and zona fasciculata separated by an undifferentiated zone in the rat, but not in the mouse. In the present study we aimed to determine the mRNA expression patterns of Sonic hedgehog and the hedgehog signaling pathway components Patched-1 and Gli1 in the developing and adult rat adrenal. Sonic hedgehog expression was detected at the periphery of the cortex in cells lacking CYP11B1 and CYP11B2 expression, while signal-receiving cells were localized in the overlying capsule mesenchyme. Using combined in situ hybridization and immunohistochemistry we found that the cells expressing Sonic hedgehog lie between the CYP11B2 and CYP11B1 layers, and thus Sonic hedgehog expression defines one cell population of the undifferentiated zone.

  11. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects.

  12. On Again, Off Again Effects of Gonadectomy on the Acoustic Startle Reflex in Adult Male Rats

    PubMed Central

    Turvin, J.C.; Messer, W.S.

    2007-01-01

    Numerous studies have shown sex and/or estrous cycle differences in the acoustic startle reflex (ASR) and its prepulse inhibition (PPI) in humans and animals. However, few have examined the effects of hormone manipulations on these behaviors. This study paired gonadectomy (GDX) in adult male rats with testing for ASR and PPI at 2, 4, 9, 16, 23, 30 and 37 days after surgery. Initial studies of control, GDX and GDX rats given testosterone propionate revealed no group differences in PPI, but did reveal phasic facilitation of the ASR in GDX rats that was greatest on the first and final testing sessions and that was attenuated by testosterone. A second study addressing roles for estrogen and androgen signaling tested new control and GDX rats along with GDX rats given estradiol or the non-aromatizable androgen, 5-alpha-dihydrotestosterone and revealed no group differences in PPI, and increases in ASR in GDX rats that were largest during the first and final testing sessions and that were attenuated by both hormone replacements. However, while responses in GDX rats given testosterone were similar to those of controls, ASR in estradiol- and to a lesser extent in dihydrotestosterone-treated GDX rats were typically lower than in controls. This may suggest that hormone modulation of the ASR requires synergistic estrogen and androgen actions. In the male brain where this can be achieved by local steroid metabolism, the enzymes responsible, e.g., aromatase, could help identify loci in the startle circuitry that may be especially relevant for the hormone modulation observed. PMID:17169383

  13. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  14. Leptin Attenuates the Contractile Function of Adult Rat Cardiomyocytes Involved in Oxidative Stress and Autophagy

    PubMed Central

    Luo, Liu-Jin; Liu, Ying-Ping; Yuan, Xun; Zhang, Gui-Ping; Hou, Ning; Wu, Xiao-Qian; Luo, Jian-Dong; Zhang, Gen-Shui

    2016-01-01

    Background Leptin has been identified as an important protein involved in obesity. As a chronic metabolic disorder, obesity is associated with a high risk of developing cardiovascular and metabolic diseases, including heart failure. The aim of this paper was to investigate the effects and the mechanism of leptin on the contractile function of cardiomyocytes in the adult rat. Methods Isolated adult rat cardiomyocytes were exposed to leptin (1, 10, and 100 nmol/L) for 1 hour. The calcium transients and the contraction of adult rat cardiomyocytes were recorded with SoftEdge MyoCam system. Apocynin, tempol and rapamycin were added respectively, and Western blotting was employed to evaluate the expression of LC3B and Beclin-1. Results The peak shortening and maximal velocity of shortening/relengthening (± dL/dtmax) of cell shortening were significantly decreased, and the time to 50% relengthening was prolonged with leptin perfusion. Leptin also significantly reduced the baseline, peak and time to 50% baseline of calcium transient. Leptin attenuated autophagy as indicated by decreased LC3-II and Beclin-1. All of the abnormalities were significantly attenuated by apocynin, tempol or rapamycin. Conclusions Our results indicated that leptin depressed the intracellular free calcium and myocardial systolic function via increasing oxidative stress and inhibiting autophagy. PMID:27899860

  15. Morphological alterations of central nervous system (CNS) myelin in vanadium (V)-exposed adult rats.

    PubMed

    García, Graciela B; Quiroga, Ariel D; Stürtz, Nelson; Martinez, Alejandra I; Biancardi, María E

    2004-08-01

    In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of vanadium in behavioral alterations and in brain lipid peroxidation was also investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days. Open field and rotarod tests were performed the day after the last dose had been administered and then animals were sacrificed by different methods for histological and lipid peroxidation studies. The present results show that intraperitoneal administration of V(+5) to adult rats resulted in changes in locomotor activity, specific myelin stainings and lipid peroxidation in some brain areas. They support the notion that CNS myelin could be a preferential target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms underlying this action could affect the myelin sheath leading to behavioral perturbations.

  16. A new protocol for cultivation of predegenerated adult rat Schwann cells.

    PubMed

    Pietrucha-Dutczakv, Marita; Marcol, Wiesław; Francuz, Tomasz; Gołka, Dariusz; Lewin-Kowalik, Joanna

    2014-09-01

    The purpose of this study was to optimize the methodology of cultivation of predegenerated Schwann cells (SCs). SCs were isolated from 7-day-predegenerated sciatic nerves of adult rats. We applied commercially available culture medium for cultivation of endothelial cells endothelial cell culture medium (EBM-2) instead of Dulbecco's Modified Eagle's Medium commonly used to culture adult Schwann cells. Additionally, cell culture medium was supplemented with factors specifically supporting SCs growth as: bovine pituitary extract (5 μg/ml), heregulin (40 ng/ml) and insulin (2.5 ng/ml). Similarly to the reports of others authors, we did not observe any beneficial effects of Forskolin application, so we didn't supplement our medium with it. Cell culture purity was determined by counting the ratio of GFAP, N-Cadherin and NGFR p75-positive cells to total number of cells. About 94-97 % of cells were confirmed as Schwann cells. As a result, we obtained sufficient number and purity of Schwann cells to be applied in different experimental models in rats. EBM-2 medium coated with fibronectin was the best for cultivation of adult rat Schwann cells.

  17. Antipsychotic-induced suppression of locomotion in juvenile, adolescent and adult rats.

    PubMed

    Wiley, Jenny L

    2008-01-14

    Schizophrenia is a serious psychiatric disorder that is most frequently treated with the administration of antipsychotics. Although onset of schizophrenia typically occurs in late adolescence, the majority of preclinical research on the behavioral effects of antipsychotics and their mechanism(s) of action has been conducted on adult male animals. In this study, the acute effects of haloperidol (0.03-0.3 mg/kg, i.p.) and clozapine (1-10 mg/kg, i.p.) on locomotor activity were examined in juvenile [postnatal day 22 (PN22)], adolescent (PN40), and adult (>PN70) rats of both sexes. Subsequently, in order to determine whether tolerance to the activity suppressive effects of these drugs would occur in adolescents, PN40 rats were dosed and assessed for an additional nine days. While all groups exhibited some degree of suppression following acute administration of both drugs, juvenile rats were considerably more sensitive to this effect. With sub-chronic administration during late adolescent development (PN40-PN49), tolerance failed to develop. These results emphasize the importance of age in pharmacological characterization of antipsychotics and suggest that pre-adolescents may have enhanced sensitivity to the motor effects of these drugs. Further, they suggest that, similar to adults, older adolescents may not develop tolerance to the activity suppression induced by these two antipsychotics.

  18. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    PubMed Central

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-01-01

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms. PMID:24806340

  19. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    PubMed Central

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  20. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  1. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    PubMed

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  2. Juvenile exposure to methamphetamine attenuates behavioral and neurochemical responses to methamphetamine in adult rats.

    PubMed

    McFadden, Lisa M; Carter, Samantha; Matuszewich, Leslie

    2012-04-01

    Previous research has shown that children living in clandestine methamphetamine (MA) labs are passively exposed to the drug [1]. The long-term effects of this early exposure on the dopaminergic systems are unknown, but may be important for adult behaviors mediated by dopamine, such as drug addiction. The current study sought to determine if juvenile exposure to low doses of MA would lead to altered responsiveness to the stimulant in adulthood. Young male and female rats (PD20-34) were injected daily with 0 or 2 mg/kg MA or left undisturbed and then tested at PD90. In the open field, adult rats exposed to MA during preadolescence had reduced locomotor activity compared to control non-exposed rats following an acute injection of MA (2 mg/kg). Likewise, methamphetamine-induced dopamine increases in the dorsal striatum were attenuated in male and female rats that had been exposed to MA as juveniles, although there were no changes in basal in vivo or ex vivo dopamine levels. These findings suggest that exposure of juveniles to MA leads to persistent changes in the behavioral and neurochemical responses to stimulants in adulthood.

  3. Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats.

    PubMed

    Moreira, R M; Borges, P P; Lisboa, P C; Curty, F H; Moura, E G; Pazos-Moura, C C

    2000-09-01

    Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0. 25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro.

  4. Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.

    PubMed

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Ribeiro, Karine F; Petronilho, Fabrícia; Vuolo, Francieli; Colpo, Gabriela D; Pfaffenseller, Bianca; Kapczinski, Flávio; Dal-Pizzol, Felipe; Quevedo, João

    2013-04-01

    A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-α and IL-1β cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (p<0.05). Deprived rats treated with saline presented a decrease on BDNF levels in the amygdala (p<0.05), compared with all other groups. The IL-10 levels were decreased in the serum (p<0.05). TNF-α and IL-1β levels were increased in the serum and CSF of deprived rats treated with saline (p<0.05). Interestingly, imipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (p<0.05). Finally, these findings further support a relationship between immune activation, neurotrophins and the depression, and considering the action of imipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system.

  5. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    PubMed Central

    Eweka, Andrew Osayame; Eweka, Abieyuwa

    2010-01-01

    Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24), with average weight of 220g were randomly assigned into two treatments (A & B) of (n=16) and Control (c) (n=8) groups. The rats in the treatment groups (A & B) received 0.1g (500mg/kg body weight) and 0.2g (1000mg/kg body weight) of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c) received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings. PMID:22624138

  6. A spaceflight study of synaptic plasticity in adult rat vestibular maculas

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1994-01-01

    Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but

  7. Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata.

    PubMed

    Li, Mingqiang; Nie, Lihong; Hu, Yajie; Yan, Xiang; Xue, Lian; Chen, Li; Zhou, Hua; Zheng, Yu

    2013-12-01

    The present experiments were carried out to investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of rats and effects of chronic intermittent hypoxia (CIH) on its expression. Sprague Dawley adult rats were randomly divided into two groups, including control (Con) group and CIH group. The endogenous production of hydrogen sulfide (H2S) in medulla oblongata tissue homogenates was measured using the methylene blue assay method, 3MST mRNA and protein expression were analyzed by RT-PCR and Western blotting, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of rats was investigated with immunohistochemical technique. CIH elevated the endogenous H2S production in rat medulla oblongata (P<0.01). The RT-PCR and Western blotting analyses showed that 3MST mRNA and protein were expressed in the medulla oblongata of rats and CIH promoted their expression (P<0.01). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N and Amb, but not in FN and NTS, were significantly increased in CIH group (P<0.05). In conclusion, 3MST exists in the neurons of medullary respiratory nuclei and its expression can be up-regulated by CIH in adult rat, suggesting that 3MST-H2S pathway may be involved in regulation of respiration and protection on medullary respiratory centers from injury induced by CIH.

  8. IGF-I redirects doublecortin-positive cell migration in the normal adult rat brain.

    PubMed

    Maucksch, C; McGregor, A L; Yang, M; Gordon, R J; Yang, M; Connor, B

    2013-06-25

    The migration of subventricular zone (SVZ)-derived neural precursor cells through the rostral migratory stream (RMS) to the olfactory bulb is tightly regulated by local micro-environmental cues. Insulin-like Growth Factor-I (IGF-I) can stimulate the migration of several neuronal cell types and acts as a 'departure' factor in the avian SVZ. To establish whether IGF-I can also act as a migratory factor for adult neuronal precursor cells in vivo, in addition to its well established role in precursor cell proliferation and differentiation, we used AAV2-mediated gene transfer to produce ectopic expression of IGF-I in the normal adult rat striatum. We then assessed whether the expression of IGF-I would recruit SVZ-derived neuronal precursor cells from the RMS into the striatum. Ectopic expression of IGF-I in the normal adult rat brain significantly increased the number of doublecortin (Dcx)-positive cells and the extent of their migration into the striatum 4 and 8 weeks after AAV2-IGF-I injection but did not promote neuronal differentiation. In vitro migration assays confirmed that IGF-I is an inducer of migration and directs SVZ-derived adult neuronal precursor cell migration by both chemotaxis and chemokinesis. These results demonstrate that overexpression of IGF-I in the normal adult rat brain can override the normal cues directing precursor cell migration along the RMS and can redirect precursor cell migration into a non-neurogenic region. Enhanced expression of IGF-I following brain injury may therefore act as a diffusible factor mediating precursor cell migration to areas of neuronal cell damage.

  9. Machine Learning Capabilities of a Simulated Cerebellum.

    PubMed

    Hausknecht, Matthew; Li, Wen-Ke; Mauk, Michael; Stone, Peter

    2017-03-01

    This paper describes the learning and control capabilities of a biologically constrained bottom-up model of the mammalian cerebellum. Results are presented from six tasks: 1) eyelid conditioning; 2) pendulum balancing; 3) proportional-integral-derivative control; 4) robot balancing; 5) pattern recognition; and 6) MNIST handwritten digit recognition. These tasks span several paradigms of machine learning, including supervised learning, reinforcement learning, control, and pattern recognition. Results over these six domains indicate that the cerebellar simulation is capable of robustly identifying static input patterns even when randomized across the sensory apparatus. This capability allows the simulated cerebellum to perform several different supervised learning and control tasks. On the other hand, both reinforcement learning and temporal pattern recognition prove problematic due to the delayed nature of error signals and the simulator's inability to solve the credit assignment problem. These results are consistent with previous findings which hypothesize that in the human brain, the basal ganglia is responsible for reinforcement learning, while the cerebellum handles supervised learning.

  10. Susceptibility of the cerebellum to thiamine deficiency.

    PubMed

    Mulholland, Patrick J

    2006-01-01

    Thiamine or vitamin B(1), an essential nutrient absorbed from the diet, is involved in vital brain metabolic and cellular functions, including carbohydrate metabolism and neurotransmitter production. Diencephalic regions and, in particular, the cerebellum demonstrate lesions in cases of prolonged thiamine deficiency, such as that observed in alcohol-dependent individuals or in patients with cancer or AIDS. The purpose of this review is to demonstrate recent evidence of cerebellar dysfunction resulting from thiamine deficiency and to assemble theories as to why the cerebellum may be sensitive to this type of insult. A brief outline on cerebellar structure and function, as well as a short discussion on thiamine and thiamine deficiency are provided before detailing the conditions and mechanisms underlying thiamine deficiency-induced cerebellar dysfunction. Although much is known regarding cell loss from a lack of thiamine, further work is still required to identify the sequelae of events leading to the susceptibility of the cerebellum to injury stemming from a thiamine deficient diet or impaired thiamine utilization.

  11. The evolution of the vertebrate cerebellum: absence of a proliferative external granule layer in a basal ray-finned fish

    PubMed Central

    Butts, Thomas; Modrell, Melinda S.; Baker, Clare V. H.; Wingate, Richard J. T.

    2016-01-01

    The cerebellum represents one of the most morphologically variable structures in the vertebrate brain. To shed light on its evolutionary history, we have examined the molecular anatomy and proliferation of the developing cerebellum of the North American paddlefish, Polyodon spathula. Absence of an external proliferative cerebellar layer and the restriction of Atonal1 expression to the rhombic lip and valvular primordium demonstrate that transit amplification in a cerebellar external germinal layer, a prominent feature of amniote cerebellum development, is absent in paddlefish. Furthermore, expression of Sonic hedgehog, which drives secondary proliferation in the mouse cerebellum, is absent from the paddlefish cerebellum. These data are consistent with what has been observed in zebrafish and suggest that the transit amplification seen in the amniote cerebellum was either lost very early in the ray-finned fish lineage or evolved in the lobe-finned fish lineage. We also suggest that the Atoh1-positive proliferative valvular primordium may represent a synapomorphy (shared derived character) of ray-finned fishes. The topology of valvular primordium development in paddlefish differs significantly from that of zebrafish and correlates with the adult cerebellar form. The distribution of proliferative granule cell precursors in different vertebrate taxa is thus the likely determining factor in cerebellar morphological diversity. PMID:24617988

  12. Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase activity in pre-pubertal and adult rats.

    PubMed

    Marassi, Michelle P; Fortunato, Rodrigo S; da Silva, Alba C Matos; Pereira, Valmara S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia M Corrêa

    2007-01-01

    Iodothyronine deiodinase activities are regulated by sex steroids; however, the mechanisms underlying the reported sexual dimorphism are poorly defined. In the present report, we aimed to investigate whether type 1 deiodinase (D1) sexual dimorphism exists early in sexual development by studying pre-pubertal male (Pm) and female (Pf) rats, as well as adult controls (C) and gonadectomized male and females rats. Adult male Wistar rats were studied 21 days after orchiectomy (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher in pre-pubertal (P) rats than in the matching adults, with no difference between genders, although in adult males T3 was significantly lower than in females. There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal (P) rats was within the adult female range, and both were significantly lower than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult females, liver D1 activity was lower, while in adult males it was higher than in P rats. The same pattern of D1 activity was found in kidney. In thyroid and pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all significantly lower than in the adult male. There were no differences in serum T3 and T4 between C and Tex males, but serum TSH was significantly decreased in Tex rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes were detected in thyroid and pituitary. In Ovx females, T3 was significantly lower than in the C group. Serum T4 was significantly decreased by estradiol replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged. Eb replacement increased liver and thyroid D1 activity, but in the kidney, only the highest estradiol dose promoted a significant D1 increase. In conclusion, in males, hepatic and renal D1 activity appears to be significantly influenced by

  13. Excitation and inhibition jointly regulate cortical reorganization in adult rats.

    PubMed

    Benali, Alia; Weiler, Elke; Benali, Youssef; Dinse, Hubert R; Eysel, Ulf T

    2008-11-19

    The primary somatosensory cortex (SI) retains its capability for cortical reorganization after injury or differential use into adulthood. The plastic response of SI cells to peripheral stimulation is characterized by extension of cortical representations accompanied by changes of the receptive field size of neurons. We used intracortical microstimulation that is known to enforce local, intracortical synchronous activity, to induce cortical reorganization and applied immunohistochemical methods in the same individual animals to investigate how plasticity in the cortical topographic maps is linked to changes in the spatial layout of the inhibitory and excitatory neurotransmitter systems. The results reveal a differential spatiotemporal pattern of upregulation and downregulation of specific factors for an excitatory (glutamatergic) and an inhibitory (GABAergic) system, associated with changes of receptive field size and reorganization of the somatotopic map in the rat SI. Predominantly local mechanisms are the specific reduction of the calcium-binding protein parvalbumin in inhibitory neurons and the low expression of the activity marker c-Fos. Reorganization in the hindpaw representation and in the adjacent SI cortical areas (motor cortex and parietal cortex) is accompanied by a major increase of the excitatory transmitter glutamate and c-Fos. The spatial extent of the reorganization appears to be limited by an increase of glutamic acid decarboxylase and the inhibitory transmitter GABA. The local and medium-range net effects are excitatory and can facilitate receptive field enlargements and cortical map expansion. The longer-range increase of inhibition appears suited to limit these effects and to prevent neurons from pathological hyperexcitability.

  14. Perinatal exposure to xenoestrogens affects pain in adult female rats.

    PubMed

    Ceccarelli, Ilaria; Fiorenzani, Paolo; Della Seta, Daniele; Massafra, Cosimo; Cinci, Giuliano; Bocci, Anna; Aloisi, Anna Maria

    2009-01-01

    Estrogens have a variety of effects in addition to their action on reproductive structures, including permanent effects on the Central Nervous System (CNS). Therefore environmental chemicals with estrogenic activity (xenoestrogens) can potentially affect a number of CNS functions. In the present experiment, female rats receiving ethynylestradiol (EE) or methoxychlor (MXC) via the mothers during pregnancy (pre) or lactation (post) were tested in comparison with females born from mothers treated with OIL. The Object Recognition, Plantar and Formalin tests were carried out to evaluate the effects of these compounds on integrated functions such as memory and pain. Testosterone and estradiol plasma levels were determined by RIA. The results of the Object Recognition and Plantar tests did not differ among groups. However the groups differed in the Formalin test since flexing duration was higher in the EE- and MXC-pre groups than in the EE- and MXC-post and OIL groups. Estradiol plasma levels were higher in EE-pre than in the other groups. These results confirm the possibility that estrogen-like compounds (EE and MXC) can affect complex neural processes like pain when taken during critical stages of CNS development.

  15. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    PubMed

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults.

  16. Age and sex differences in reward behavior in adolescent and adult rats.

    PubMed

    Hammerslag, Lindsey R; Gulley, Joshua M

    2014-05-01

    Compared to adults, adolescents are at heightened risk for drug abuse and dependence. One of the factors contributing to this vulnerability may be age-dependent differences in reward processing, with adolescents approaching reward through stimulus-directed, rather than goal-directed, processes. However, the empirical evidence for this in rodent models of adolescence, particularly those that investigate both sexes, is limited. To address this, male and female rats that were adolescents (P30) or adults (P98) at the start of the experiment were trained in a Pavlovian approach (PA) task and were subsequently tested for the effects of reward devaluation, extinction, and re-acquisition. We found significant interactions between age and sex: females had enhanced acquisition of PA and poorer extinction, relative to males, while adolescents and females were less sensitive to reward devaluation than male adults. These results suggest that females and adolescents exhibit reward behavior that is more stimulus-directed, rather than goal-directed.

  17. Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats.

    PubMed

    Attella, M J; Hoffman, S W; Stasio, M J; Stein, D G

    1989-07-01

    Adult, male Sprague-Dawley rats received 100 mg/kg Ginkgo biloba extract (GBE) intraperitoneally for 30 days. GBE reduced overall activity and decreased sensitivity to light in the open field maze. The rats were also less responsive to noxious stimuli after 13 days of treatment with GBE. After the last injection, all subjects were trained on a delayed-spatial alternation task. Subsequent to acquisition of the spatial task, the rats received either sham operations and saline or bilateral frontal cortex lesions treated with either saline or GBE. Thirty additional days of treatment began on the day of injury, and open field behavior, analgesia, and metabolic activity measurements were again measured. The rats with lesions treated with saline were more active than their GBE-treated counterparts and sham controls but there were no differences in response to illumination or noxious stimuli. Retention of the delayed-spatial alternation indicated that rats with lesions treated with GBE were less impaired than brain-injured subjects receiving saline treatment. Histological examination showed that GBE reduced the extent of brain swelling in response to the injury.

  18. Effect of restraint and copper deficiency on blood pressure and mortality of adult rats

    SciTech Connect

    Klevay, L.M.; Halas, E.S. )

    1989-02-01

    The etiology of most hypertension is unknown; stress is thought to elevate blood pressure. Male, weanling Sprague-Dawley rats were fed a purified diet plus a drinking solution containing 10{mu}g Zn and 2{mu}g Cu/ml (acetate sulfate, respectively). Systolic blood pressure was measured without anesthesia. After being matched by mean weight (280g) and blood pressure into 4 groups of 15, groups 1 and 2 received a drinking solution without copper. After 24 days rats in groups 2 and 4 were restrained for 45 min. daily (A.M.) for 23 days in a small plastic cage (19{times}6{times}6 cm). Final pressures were affected both by stress and dietary Cu: group 1, 119; group 2, 131; group 3, 114; group 4, 123 mm Hg. One rat in each of groups 1, 3, 4 and 10 rats in group 2, died. Among these latter hemorrhage was prominent, blood being found in bladder (2), gut (2), peritoneum (2) and scrotum (1). Copper deficiency decreased cooper in both adrenal gland and liver by 58% and in heart by 29% restraint was without effect. Cardiac sodium was increased 6% only by deficiency. Results confirm the hypertensive effect of copper deficiency in adult rats and reveal that the stress of restraint increases blood pressure. Copper deficiency plus stress is harmful.

  19. Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

    PubMed Central

    Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

    2014-01-01

    Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

  20. Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure.

    PubMed

    Gigante, Eduardo D; Santerre, Jessica L; Carter, Jenna M; Werner, David F

    2014-08-01

    Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults.

  1. Effect of manganese on the concentration of amino acids in different regions of the rat brain.

    PubMed

    Lipe, G W; Duhart, H; Newport, G D; Slikker, W; Ali, S F

    1999-01-01

    The present study was designed to determine if chronic exposure of weanlings and adult rats to Mn produces significant alterations in amino acid concentrations in different regions of the rat brain. Weanling (30 day old) and adult (90 day old) male rats were exposed to 10 and 20 mg Mn/kg body weight per day, by gavage, for 30 days. Forty-eight hours after the last dose, animals were sacrificed by decapitation and brains were dissected into different regions to determine the concentration of amino acids by HPLC/EC. A dose dependent decrease in body weight gain was found in the adult, but not in the weanling rats. Significant increases occurred in concentrations of aspartate, glutamate, glutamine, taurine and gamma-aminobutyric acid (GABA) in the cerebellum of the adult rats dosed with 20 mg/kg per day, Mn. A significant decrease in the concentration of glutamine was observed in caudate nucleus and hippocampus of weanling rats dosed with 10 mg/kg, Mn. These data suggest that chronic Mn exposure can produce a decrease in body weight gain in adult rats and alterations in amino acids in different regions of weanling and adult rat brains.

  2. Circadian rhythm of intraocular pressure in the adult rat.

    PubMed

    Lozano, Diana C; Hartwick, Andrew T E; Twa, Michael D

    2015-05-01

    Ocular hypertension is a risk factor for developing glaucoma, which consists of a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells and subsequent irreversible vision loss. Our understanding of how intraocular pressure damages the optic nerve is based on clinical measures of intraocular pressure that only gives a partial view of the dynamic pressure load inside the eye. Intraocular pressure varies over the course of the day and the oscillator regulating these daily changes has not yet been conclusively identified. The purpose of this study was to compare and contrast the circadian rhythms of intraocular pressure and body temperature in Brown Norway rats when these animals are housed in standard light-dark and continuous dim light (40-90 lux) conditions. The results from this study show that the temperature rhythm measured in continuous dim light drifted forward relative to external time, indicating that the rhythm was free running and being regulated by an internal biological clock. Also, the results show that there is a persistent, but dampened, circadian rhythm of intraocular pressure in continuous dim light and that the circadian rhythms of temperature and intraocular pressure are not synchronized by the same central oscillator. We conclude that once- or twice-daily clinical measures of intraocular pressure are insufficient to describe intraocular pressure dynamics. Similarly, our results indicate that, in experimental animal models of glaucoma, the common practice of housing animals in constant light does not necessarily eliminate the potential influence of intraocular pressure rhythms on the progression of nerve damage. Future studies should aim to determine whether an oscillator within the eye regulates the rhythm of intraocular pressure and to better characterize the impact of glaucoma on this rhythm.

  3. Differential Effects of Inhaled Toluene on Locomotor Activity in Adolescent and Adult Rats

    PubMed Central

    Batis, Jeffery C.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8,000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm “air” controls at both ages. These changes depended upon when activity was measured – during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the “recovery” period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen

  4. Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

    PubMed Central

    Friedman, LK; Slomko, AM; Wongvravit, JP; Naseer, Z; Hu, S; Wan, WY; Ali, SS

    2015-01-01

    Background and Purpose: The efficacy of retigabine (RGB), a positive allosteric modulator of K+ channels indicated for adjunct treatment of partial seizures, was studied in two adult models of kainic acid (KA)-induced status epilepticus to determine it’s toleratbility. Methods: Retigabine was administered systemiclly at high (5 mg/kg) and low (1–2 mg/kg) doses either 30 min prior to or 2 hr after KA-induced status epilepticus. High (1 µg/µL) and low (0.25 µg/µL) concentrations of RGB were also delivered by intrahippocampal microinjection in the presence of KA. Results: Dose-dependent effects of RGB were observed with both models. Lower doses increased seizure behavior latency and reduced the number of single spikes and synchronized burst events in the electroencephalogram (EEG). Higher doses worsened seizure behavior, produced severe ataxia, and increased spiking activity. Animals treated with RGB that were resistant to seizures did not exhibit significant injury or loss in GluR1 expression; however if stage 5–6 seizures were reached, typical hippocampal injury and depletion of GluR1 subunit protein in vulernable pyramidal fields occurred. Conclusions: RGB was neuroprotective only if seizures were significantly attenuated. GluR1 was simultaneously suppressed in the resistant granule cell layer in presence of RGB which may weaken excitatory transmission. Biphasic effects observed herein suggest that the human dosage must be carefully scrutinized to produce the optimal clinical response. PMID:26819936

  5. Noise exposure during early development impairs the processing of sound intensity in adult rats.

    PubMed

    Bures, Zbynek; Grécová, Jolana; Popelár, Jirí; Syka, Josef

    2010-07-01

    During the early postnatal development of rats, the structural and functional maturation of the central auditory nuclei strongly relies on the natural character of the incoming neural activity. Even a temporary deprivation in the critical period results in a deterioration of neuronal responsiveness in adult animals. We demonstrate that besides the poorer frequency selectivity of neurons in the impaired animals reported previously [Grecova et al. (2009)Eur. J. Neurosci. 29, 1921-1930], the neuronal representation of sound intensity is significantly affected. Rate-intensity functions of inferior colliculus neurons were recorded in anaesthetized adult rats that were exposed to intense noise at postnatal day 14, and compared with those obtained in age-matched controls. Although the response thresholds were similar in the exposed and control rats, the neurons in the exposed animals had a longer first-spike latency, a narrower dynamic range, lower maximum response magnitudes and a steeper slope of the rate-intensity functions. The percentage of monotonic neurons was significantly lower in the exposed animals. The observed anomalies were confined to the mid- and high-frequency regions, whereas no significant changes were found in the low-frequency neurons. The altered parameters of the individual rate-intensity functions led also to differences in the cumulative responses. We conclude that a brief noise exposure during the critical period leads to a frequency-dependent alteration of the sound intensity representation in the inferior colliculus of adult rats. The results suggest that such impairments may appear in individuals with normal hearing thresholds, but with a history of noise exposure very early in childhood.

  6. Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters.

    PubMed

    Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

    2007-04-15

    Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.

  7. Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

    PubMed

    Farag, Mahmoud M; Selima, Eman A; Salama, Mona A

    2013-11-15

    The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

  8. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    PubMed

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  9. SEXUAL INTERACTIONS WITH UNFAMILIAR FEMALES REDUCE HIPPOCAMPAL NEUROGENESIS AMONG ADULT MALE RATS

    PubMed Central

    Spritzer, Mark D.; Curtis, Molly G.; DeLoach, Julia P.; Maher, Jack; Shulman, Leanne M.

    2016-01-01

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of BrdU (200 mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30 min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohisotchemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. There were no differences in the amount of sexual behavior (mounts, intromissions, ejaculations, or contact time) that the familiar and unfamiliar groups engaged in, indicating that the differences in neurogenesis were not due to the relative amounts of sexual activity. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect

  10. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  11. Histological correlates of N40 auditory evoked potentials in adult rats after neonatal ventral hippocampal lesion: animal model of schizophrenia.

    PubMed

    Romero-Pimentel, A L; Vázquez-Roque, R A; Camacho-Abrego, I; Hoffman, K L; Linares, P; Flores, G; Manjarrez, E

    2014-11-01

    The neonatal ventral hippocampal lesion (NVHL) is an established neurodevelopmental rat model of schizophrenia. Rats with NVHL exhibit several behavioral, molecular and physiological abnormalities that are similar to those found in schizophrenics. Schizophrenia is a severe psychiatric illness characterized by profound disturbances of mental functions including neurophysiological deficits in brain information processing. These deficits can be assessed by auditory evoked potentials (AEPs), where schizophrenics exhibit abnormalities in amplitude, duration and latency of such AEPs. The aim of the present study was to compare the density of cells in the temporal cerebral cortex and the N40-AEP of adult NVHL rats versus adult sham rats. We found that rats with NVHL exhibit significant lower amplitude of the N40-AEP and a significant lower number of cells in bilateral regions of the temporal cerebral cortex compared to sham rats. Because the AEP recordings were obtained from anesthetized rats, we suggest that NVHL leads to inappropriate innervation in thalamic-cortical pathways in the adult rat, leading to altered function of cortical networks involved in processing of primary auditory information.

  12. Overlapping neural circuits for visual attention and eye movements in the human cerebellum.

    PubMed

    Striemer, Christopher L; Chouinard, Philippe A; Goodale, Melvyn A; de Ribaupierre, Sandrine

    2015-03-01

    Previous research in patients with cerebellar damage suggests that the cerebellum plays a role in covert visual attention. One limitation of some of these studies is that they examined patients with heterogeneous cerebellar damage. As a result, the patterns of reported deficits have been inconsistent. In the current study, we used functional neuroimaging (fMRI) in healthy adults (N=14) to examine whether or not the cerebellum plays a role in covert visual attention. Participants performed two covert attention tasks in which they were cued exogenously (with peripheral flashes) or endogenously (using directional arrows) to attend to marked locations in the visual periphery without moving their eyes. We compared BOLD activation in these covert attention conditions to a number of control conditions including: the same attention tasks with eye movements, a target detection task with no cueing, and a self-paced button-press task. Subtracting these control conditions from the covert attention conditions allowed us to effectively remove the contribution of the cerebellum to motor output. In addition to the usual fronto-parietal networks commonly engaged by these attention tasks, lobule VI of the vermis in the cerebellum was also activated when participants performed the covert attention tasks with or without eye movements. Interestingly, this effect was larger for exogenous compared to endogenous cueing. These results, in concert with recent patient studies, provide independent yet converging evidence that the same cerebellar structures that are involved in eye movements are also involved in visuospatial attention.

  13. Chronic nicotine alters cannabinoid-mediated locomotor activity and receptor density in periadolescent but not adult male rats

    PubMed Central

    Werling, Linda L.; Reed, Stephanie Collins; Wade, Dean; Izenwasser, Sari

    2009-01-01

    A significant number of youths use cigarettes, and more than half of the youths who smoke daily also use illicit drugs. The focus of these studies is on how exposure to nicotine affects subsequent responses to both nicotine and cannabinoids in adolescents compared with adults. We have shown previously that chronic treatment with nicotine produces sensitization to its locomotor-activating effects in female and adult rats but not male adolescent rats. To better understand the effects of nicotine on adolescent and adult rats, rats were injected with nicotine or saline for 7 days and, on day 8, either challenged with delta-9-tetrahydrocannabinol (Δ9-THC) or the cannabinoid agonist CP 55,940 and tested for locomotor activity, or the brains were removed for quantitative autoradiography studies of the cannabinoid1 receptor. A separate group of rats was treated with nicotine plus the cannabinoid antagonist AM 251 and then challenged with CP 55,940. In adolescent male rats, nicotine administration led to sensitization to the locomotor-decreasing effects of both Δ9-THC and CP 55,940, but in adult male rats, the response to either drug was unchanged compared to controls. The effect of nicotine on CP 55,940-mediated locomotor activity was blocked by co-administration of AM 251 with the nicotine. Further, cannabinoid receptor density was increased in the prelimbic prefrontal cortex, ventral tegmental area, and select regions of the hippocampus in adolescent male rats pretreated with nicotine compared to vehicle-treated controls. There were no significant changes in cannabinoid receptor binding, however, in any of the brain regions examined in adult males pretreated with nicotine. The prelimbic prefrontal cortex and the hippocampus have been shown previously to be involved in stimulant reinforcement; thus it is possible that these changes contribute to the unique behavioral effects of chronic nicotine and subsequent drug administration in adolescents compared with adults. PMID

  14. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    SciTech Connect

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  15. Gender differences in the effect of adult amphetamine on cognitive functions of rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Nohejlová, K; Slamberová, R

    2014-08-15

    Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure.

  16. Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats.

    PubMed

    Takeuchi, Takashi; Kitagawa, Hiroshi; Harada, Etsumori

    2004-05-01

    Using adult rats, the characteristic transporting system for lactoferrin (LF) from intestinal lumen into the blood circulation was investigated. The rats were randomly divided into two groups, a non-collected thoracic lymph (NC) group and a collected thoracic lymph (LC) group. Peripheral blood and thoracic lymph were collected from a jugular vein and a thoracic lymph duct, respectively, under anaesthesia. Bovine LF (bLF) was infused into the duodenal lumen by needle over a 1-min period at a dose of 1 g kg(-1). The transported bLF in the plasma and lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Morphological investigation was also carried out in the intestine, lymph node, and liver. Following intraduodenal administration of bLF, the transported bLF in the NC group was detected in the plasma, and reached a peak value at 2 h. Furthermore, the bLF concentration in the thoracic duct lymph fluid in the LC group increased significantly, and peaked 2 h after the administration. In addition, bLF was not detected in the plasma of the LC group. Immunohistochemical analysis clearly showed anti-bLF positive particles in the epithelial cells of the apical villi. The striated border and baso-lateral membrane were also bLF positive. These results suggest that intraduodenally infused bLF is transported into the blood circulation via the lymphatic pathway, not via portal circulation in adult rats.

  17. Lead Exposure Induces Weight Gain in Adult Rats, Accompanied by DNA Hypermethylation

    PubMed Central

    Zhao, Li; Li, Qin; Cang, Zhen; Chen, Chi; Lu, Meng; Cheng, Jing; Zhai, Hualing; Xia, Fangzhen; Ye, Lin; Lu, Yingli

    2017-01-01

    Objective Previous studies have revealed the association of lead (Pb) exposure with obesity. DNA methylation alteration has been suggested to be one of the regulatory mechanisms of obesity. We aimed to explore whether Pb exposure is related with weight gain and DNA methylation alteration. Methods Male adult 8 week Wistar rats were divided into 5 groups: the normal chow diet (NCD); the NCD+0.05%Pb; the NCD+0.15%Pb; the NCD+0.45%Pb and the high fat diet. Rats were exposed to different dosages of Pb through drinking water for 21 weeks. Body weight, fasted blood glucose level, fasted insulin level, homeostasis assessment of insulin resistance (HOMA-IR) index and lipid profile were detected. Intra-peritoneal glucose tolerance test (IPGTT) was constructed to evaluate the glucose tolerance. Lipid accumulation of liver was detected and liver DNA underwent whole genome bisulfite sequencing. Results The NCD+0.05%Pb group had significantly greater weight, HOMA-IR and triglycerides, and lower glucose intolerance than the NCD group (P <0.05). This group also showed hepatic lipid accumulation. These metabolic changes were not observed in the other two Pb dosage groups. Furthermore, DNA hypermethylation extended along pathways related to glucose and lipid metabolism in NCD+0.05%Pb group. Conclusion Pb exposure resulted in dose-specific weight gain in adult Wistar rats, accompanied by alteration of DNA methylation. PMID:28107465

  18. Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.

    PubMed

    Ivy, G O; Gould, H J; Killackey, H P

    1984-07-23

    Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.

  19. Effects of moderate zinc deficiency on cognitive performance in young adult rats.

    PubMed

    Massaro, T F; Mohs, M; Fosmire, G

    1982-07-01

    Two experiments were conducted to establish a dietary zinc level which approximates a moderate deficiency in the young adult rat and to determine if a concurrent zinc deficiency affects cognitive performance. Male rats were fed varying levels of zinc in diet throughout a 17-day period. The lowest dietary level that depressed serum and bone zinc without influencing food consumption or body weight gains was observed to be 5.8 microgram Zn/g diet. Young adult rats maintained on either a zinc adequate (24.4 microgram Zn/g) or low-zinc (5.3 microgram Zn/g) diet were tested in a modified Skinner Box involving tests of visual, auditory, association, and discrimination learning. No differences were observed in the visual discrimination performance of the zinc deficient animals when compared with control counterparts. Deficits in the ability to transfer a learned association between visual and auditory stimuli were observed, however, in the deficient group during the transfer test phase. The latter performed better during the final auditory discrimination task in transferring a learned food-relevant cue.

  20. Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat.

    PubMed

    Bonomo, Isabela Teixeira; Lisboa, Patrícia Cristina; Passos, Magna Cottini Fonseca; Alves, Simone Bezerra; Reis, Adelina Martha; de Moura, Egberto Gaspar

    2008-08-01

    Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum tri-iodothyronine (T(3)). Maternal hypoprolactinemia at the end of lactation caused higher body weight in adult life, suggesting an association between maternal prolactin (PRL) level and programming of the offspring's adult body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD), liver and pituitary de-iodinase activities (D1 and/or D2), and in vitro post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into BRO - injected with 1 mg/twice a day, daily for the last 3 days of lactation, and C - control, saline-injected with the same frequency. At 180 days of age, the offspring were injected with (125)I i.p. and after 2 h, they were killed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (-51%), T(3) (-23%), and thyroxine (-21%), lower thyroid (125)I uptake (-41%), liver mGPD (-55%), and pituitary D2 (-51%) activities, without changes in the in vitro post-TRH TSH release. We show that maternal PRL suppression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.

  1. Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

    PubMed Central

    Merkley, Christina M.; Jian, Charles; Mosa, Adam; Tan, Yao-Fang; Wojtowicz, J. Martin

    2014-01-01

    Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age. PMID:25071426

  2. Functional plasticity of regenerated and intact taste receptors in adult rats unmasked by dietary sodium restriction.

    PubMed

    Hill, D L; Phillips, L M

    1994-05-01

    Unilateral chorda tympani nerve sectioning was combined with institution of a sodium-restricted diet in adult rats to determine the role that environment has on the functional properties of regenerating taste receptor cells. Rats receiving chorda tympani sectioning but no dietary manipulation (cut controls) and rats receiving only the dietary manipulation (diet controls) had normal responses to a concentration series of NaCl, sodium acetate (NaAc), and NH4Cl. However, responses from the regenerated nerve in NaCl-restricted rats (40-120 d postsectioning) to NaCl and NaAc were reduced by as much as 30% compared to controls, indicating that regenerating taste receptors are influenced by environmental (dietary) factors. Responses to NH4Cl were normal; therefore, the effect appears specific to sodium salts. Surprisingly, in the same rats, NaCl responses from the contralateral, intact chorda tympani were up to 40% greater than controls. Thus, in the same rat, there was over a twofold difference in sodium responses between the right and left chorda tympani nerves. A study of the time course of the functional alterations in the intact nerve revealed that responses to NaCl were extremely low immediately following sectioning (about 20% of the normal response), and then increased monotonically during the following 50 d until relative response magnitudes became supersensitive. This function occurred even when the cut chorda tympani was prevented from reinnervating lingual epithelia, demonstrating that events related to regeneration do not play a role in the functional properties of the contralateral side of the tongue.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    PubMed

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  4. Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

    PubMed

    Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G

    1983-01-01

    Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

  5. Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

    PubMed Central

    Shepherd, Daniel J.; Tsai, Shih-Yen; O'Brien, Timothy E.; Farrer, Robert G.; Kartje, Gwendolyn L.

    2016-01-01

    Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis. PMID:27803646

  6. GABAergic transmission and enhanced modulation by opioids and endocannabinoids in adult rat rostral ventromedial medulla

    PubMed Central

    Li, Ming-Hua; Suchland, Katherine L; Ingram, Susan L

    2015-01-01

    Neurons in the rostral ventromedial medulla (RVM) play critical and complex roles in pain modulation. Recent studies have shown that electrical stimulation of the RVM produces pain facilitation in young animals (postnatal (PN) day < 21) but predominantly inhibits pain behaviours in adults. The cellular mechanisms underlying these changes in RVM modulation of pain behaviours are not known. This is in part because whole-cell patch-clamp studies in RVM to date have been in young (PN day < 18) animals because the organization and abundance of myelinated fibres in this region make the RVM a challenging area for whole-cell patch-clamp recording in adults. Several neurotransmitter systems, including GABAergic neurotransmission, undergo developmental changes that mature by PN day 21. Thus, we focused on optimizing whole-cell patch-clamp recordings for RVM neurons in animals older than PN day 30 and compared the results to animals at PN day 10–21. Our results demonstrate that the probability of GABA release is lower and that opioid and endocannabinoid effects are more evident in adult rats (mature) compared to early postnatal (immature) rats. Differences in these properties of RVM neurons may contribute to the developmental changes in descending control of pain from the RVM to the spinal cord. PMID:25556797

  7. Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats.

    PubMed

    Doremus-Fitzwater, Tamara L; Spear, Linda P

    2011-08-01

    Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% wt/vol) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-s presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age.

  8. A computational model of the cerebellum

    SciTech Connect

    Travis, B.J.

    1990-01-01

    The need for realistic computational models of neural microarchitecture is growing increasingly apparent. While traditional neural networks have made inroads on understanding cognitive functions, more realism (in the form of structural and connectivity constraints) is required to explain processes such as vision or motor control. A highly detailed computational model of mammalian cerebellum has been developed. It is being compared to physiological recordings for validation purposes. The model is also being used to study the relative contributions of each component to cerebellar processing. 28 refs., 4 figs.

  9. Maternal isobutyl-paraben exposure alters anxiety and passive avoidance test performance in adult male rats.

    PubMed

    Kawaguchi, Maiko; Irie, Kaoru; Morohoshi, Kaori; Watanabe, Gen; Taya, Kazuyoshi; Morita, Masatoshi; Kondo, Yasuhiko; Imai, Hideki; Himi, Toshiyuki

    2009-10-01

    Isobutyl-paraben (IBP), one of the most widely used preservatives, exhibits estrogenic activity. In this study, we analyzed the effects of maternal IBP treatment on the emotional behavior and learning performance in mature offspring. Pregnant female Sprague-Dawley rats were treated with IBP via a subcutaneous Silastic capsule. Consequently, the offspring were exposed to IBP during gestation through the placentae, and before weaning through the milk. Male and female offspring were tested for emotional behavior in an open field and in an elevated plus maze at five and six weeks old, respectively. IBP-exposed male (but not female) rats spent less time in the open arms of the elevated plus maze. At 11 weeks old, all females were gonadectomized and treated chronically with 17beta-estradiol or cholesterol by Silastic capsules; all males were kept intact. They were tested for learning performance in a passive avoidance test and a Morris water maze. IBP exposure impaired the performance of males in the passive avoidance test. These findings suggest that male rats are more affected by early exposure to IBP than female rats. IBP affects their adult behavior including anxiety and learning abilities.

  10. Spermatogenetic disorders in adult rats exposed to tributyltin chloride during puberty.

    PubMed

    Yu, Wook Joon; Lee, Beom Jun; Nam, Sang Yoon; Kim, Young Chul; Lee, Yong Soon; Yun, Young Won

    2003-12-01

    Adverse effects of tributyltin (TBT) chloride were investigated on the reproductive system in male adult rats as exposed during puberty. Fifty Sprague-Dawley rats at the age of 35 days were assigned to five different groups: negative control receiving vehicle, methyltestosterone (10 mg/kg B.W.), and TBT chloride treatments (5, 10, and 20 mg/kg B.W.). Animals were treated by oral gavage for ten consecutive days and sacrificed at 5 weeks after final treatment. The treatment of TBT chloride at the high dose of 20 mg/kg B.W. significantly decreased homogenization-resistant testicular sperm counts (p<0.05). The TBT chloride treatment at the doses of 10 and 20 mg/kg B.W. also significantly decreased caudal epididymal sperm counts (p<0.01). Some of motion kinematic parameters (motility, mean angular displacement, lateral head displacement, and dance) of sperms retrieved from vasa deference were significantly decreased in rats treated with the TBT chloride at the dose of 20 mg/kg B.W. (p<0.05). These results provide a further evidence that an exposure to TBT chloride during pubertal period in male rats produces spermatogenic disorders characterized by decreasing testicular and epididymal sperm counts and some motion parameters of sperms in the vasa deference.

  11. Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex of adult rats.

    PubMed

    Bortel, Aleksandra; Nowak, Przemyslaw; Brus, Ryszard

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a noradrenergic neurotoxin which selectively damages noradrenergic projections originating from the locus coeruleus (LC). DSP-4 treatment of rats on the first and third days after birth produces a long-lasting lesion of noradrenergic neurons in the prefrontal cortex (PFC). In DSP-4-lesioned rats, studied as adults, we observed a decrease in norepinephrine content, with no significant change in the levels of dopamine, 5-hydroxytryptamine, and gamma-aminobutyric acid (GABA). There is now a well established interaction between noradrenergic and GABAergic systems, whereby the noradrenergic system is involved in the regulation of basal GABA release, while GABAergic neurons simultaneously exert tonic inhibitory regulation of LC norepinephrine neurons. We examined GABAergic neurotransmission in the norepinephrine-denervated PFC for a better appreciation of the interaction between these two systems. Treatment with the GABA transaminase inhibitor vigabatrine (VGB) increased the GABA level of PFC (tissue content) in both intact and lesioned groups. Additionally, VGB increased extracellular GABA concentration in the PFC in both control and DSP-4-lesioned animals, but the elevation of GABA was 2-fold higher in DSP-4 lesioned rats. These findings indicate that neonatal DSP-4 treatment increases GABAergic neurotransmission in the PFC of rats in adulthood, perhaps by decreasing reactivity of central GABA(A) receptors.

  12. Effects of estradiol and progesterone on vertebral collagen, glycosaminoglycans and phosphatases in ovariectomized adult rats.

    PubMed

    Gopala Krishnan, V; Arunakaran, J; Govindarajulu, P; Srinivasan, N

    2003-03-01

    Vertebral collagen, glycosaminoglycans (GAGs), tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were measured in ovariectomized (ovx) adult Wistar rats treated with estradiol (E 2 ) (10 micro g/kg BW for 35 days on alternate days, and progesterone (P 4 ) (140 micro g/kg BW for 35 days on alternate days) in E 2 + P 4 treated rats. P 4 given alone or in combination with E 2 significantly increased the levels of collagen in the vertebral bone. Neither ovx nor E 2 treatment altered the concentration of collagen in these rats. Administration of E 2 or P 4 significantly decreased the concentration of hyaluronic acid (HA), but remaining unaffected when a combination of these steroids was given. In contrast to their effect on HA, E 2 and P 4 each significantly increased the levels of chondroitin sulfate (CS) in the vertebral bone. The specific activity of ALP was decreased after ovx. E 2 and P 4 alone or in combination also registered a significant decrease in the activities of ALP and TRAP. The results suggest that E 2 and P 4 each exert definite effects on vertebral bone turnover in ovariectomized rats.

  13. Tianeptine facilitates spreading depression in well-nourished and early-malnourished adult rats.

    PubMed

    Amancio-Dos-Santos, Angela; Maia, Luciana Maria Silva de Seixas; Germano, Paula Catirina Pereira da Silva; Negrão, Yleana Danielle Dos Santos; Guedes, Rubem Carlos Araújo

    2013-04-15

    Nutritional status during development can modify the brain's electrophysiological properties and its response to drugs that reduce the serotonin availability in the synaptic cleft. Here we used cortical spreading depression (CSD) in the rat as a neurophysiological parameter to investigate the interaction between nutritional status and treatment with tianeptine, a serotonin uptake enhancer. From postnatal day 2 to 24, well-nourished and early-malnourished rat pups were s.c. injected with tianeptine (5 or 10mg/kg; 10 ml/kg) or equivalent volume of saline solution (control group). When the animals were 25-30 days old, CSD was recorded on the brain cortical surface. In the well-nourished rats, but not in the malnourished group, systemic tianeptine dose-dependently increased the CSD propagation velocity, with 10mg/kg producing a significant (P<0.05) effect. An experiment in adult rats showed that cortical topical application of tianeptine solutions (5mg/ml, 10mg/ml, and 20mg/ml) increased the CSD propagation in both the well-nourished and early-malnourished conditions. In well-nourished animals, 0.5mg/ml topical tianeptine did not affect CSD propagation, and 2mg/ml produced a small, but significant CSD acceleration. Our results indicate a facilitating action of tianeptine on CSD propagation, probably via tianeptine's pharmacological action on the serotonin system. These findings support previous data suggesting an antagonistic role of the serotoninergic system on CSD.

  14. Lifespan Changes in the Countermanding Performance of Young and Middle Aged Adult Rats

    PubMed Central

    Beuk, Jonathan; Beninger, Richard J.; Paré, Martin

    2016-01-01

    Inhibitory control can be investigated with the countermanding task, which requires subjects to make a response to a go signal and cancel that response when a stop signal is presented occasionally. Adult humans performing the countermanding task typically exhibit impaired response time (RT), stop signal response time (SSRT) and response accuracy as they get older, but little change in post-error slowing. Rodent models of the countermanding paradigm have been developed recently, yet none have directly examined age-related changes in performance throughout the lifespan. Male Wistar rats (N = 16) were trained to respond to a visual stimulus (go signal) by pressing a lever directly below an illuminated light for food reward, but to countermand the lever press subsequent to a tone (stop signal) that was presented occasionally (25% of trials) at a variable delay. Subjects were tested in 1 h sessions at approximately 7 and 12 months of age with intermittent training in between. Rats demonstrated longer go trial RT, a higher proportion of go trial errors and performed less total trials at 12, compared to 7 months of age. Consistent SSRT and post-error slowing were observed for rats at both ages. These results suggest that the countermanding performance of rats does vary throughout the lifespan, in a manner similar to humans, suggesting that rodents may provide a suitable model for behavioral impairment related to normal aging. These findings also highlight the importance of indicating the age at which rodents are tested in countermanding investigations. PMID:27555818

  15. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

    PubMed Central

    Saunders, Norman R.; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Habgood, Mark D.; Wakefield, Matthew J.; Lindsay, Helen; Stratzielle, Nathalie; Ghersi-Egea, Jean-Francois; Liddelow, Shane A.

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2–98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients. PMID:25972776

  16. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

    PubMed

    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

  17. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-12-14

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

  18. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  19. Intestinal mast cells and eosinophils in relation to Strongyloides ratti adult expulsion from the small and large intestines of rats.

    PubMed

    Shintoku, Y; Kadosaka, T; Kimura, E; Takagi, H; Kondo, S; Itoh, M

    2013-04-01

    Mucosal mast cells (MMC) play a crucial role in the expulsion of Strongyloides ratti adults from the small intestine of mice. We reported the large intestinal parasitism of S. ratti in rats, and there has been no report on MMC in the large intestine of the natural host. We studied kinetics of MMC, together with eosinophils, in the upper and lower small intestines, caecum and colon of infected rats. Two distinct phases of mastocytosis were revealed: one in the upper small intestine triggered by stimulation of 'ordinary' adults, and the other in the colon stimulated by 'immune-resistant' adults that started parasitizing the colon around 19 days post-infection. In all 4 intestinal sites, the MMC peaks were observed 5-7 days after the number of adult worms became the maximum and the height of MMC peaks appeared to be dependent on the number of parasitic adults, suggesting an important role played by worms themselves in the MMC buildup.

  20. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    PubMed

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats.

  1. Stress-induced suppression of hippocampal neurogenesis in adult male rats is altered by prenatal ethanol exposure

    PubMed Central

    SLIWOWSKA, J. H.; BARKER, J. M.; BARHA, C. K.; LAN, N.; WEINBERG, J.; GALEA, L. A. M.

    2016-01-01

    In adulthood, both alcohol (ethanol) and stress are known to suppress hippocampal neurogenesis in male rats. Similarly, most studies report that prenatal alcohol exposure (PAE) reduces cell proliferation and/or cell survival in the hippocampus of adult males. Furthermore, PAE is known to have marked effects on behavioral and hypothalamic–pituitary–adrenal (HPA) responsiveness to stressors. However, no studies have examined the modulation of adult hippocampal neurogenesis by stress in PAE animals. We hypothesized that, in accordance with previous data, PAE would suppress basal levels of adult hippocampal neurogenesis, and further that stress acting on a sensitized HPA axis would have greater adverse effects on adult hippocampal neurogenesis in PAE than in control rats. Adult male offspring from PAE, pair-fed (PF) control, and ad libitum-fed control (C) groups were subjected to restraint stress (9 days, 1 h/day) or left undisturbed. Rats were then injected with bromodeoxyuridine (BrdU) on day 10, perfused 24 h (proliferation) or 3 weeks (survival) later, and brains processed for BrdU immunohistochemistry. We found that (1) under non-stressed conditions, PAE rats had a small but statistically significant suppressive effect on levels of hippocampal neurogenesis and (2) unexpectedly, repeated restraint stress significantly reduced neurogenesis in C and PF, but not PAE rats. We speculate that the failure of PAE males to mount an appropriate (i.e. suppressive) neurogenic response to stressors, implies reduced plasticity and adaptability or resilience, which could impact negatively on hippocampal structure and function. PMID:20536332

  2. The longitudinal study of rat hippocampus influenced by stress: early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats.

    PubMed

    Jin, Fengkui; Li, Lei; Shi, Mei; Li, Zhenzi; Zhou, Jinghua; Chen, Li

    2013-06-01

    Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats' spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.

  3. Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults.

    PubMed

    Hori, S E; Powell, K J; Robertson, G S

    2007-01-05

    Recognition memory was assessed in adult rats that received bilateral injections of saline (sham lesions) or ibotenic acid (lesioned) in the ventral hippocampus as neonates (postnatal day 7, PD7) or young adult (42 days of age, PD42) using the Novel Object Recognition Test (NORT). Normal or sham-lesioned rats were able to distinguish novel from familiar objects over a 0.5 and 2 h delay between the sample and choice phases. Adult rats (PD70) lesioned as neonates performed progressively worse than sham-lesioned animals at delays of 0.5 and 2 h. A single injection of darbepoetin alfa (500 or 5000 U/kg, i.p.), given 1 h before the sample phase restored performance 0.5 or 2 h later in the choice phase to same levels as sham-lesioned rats. Adults lesioned on PD42 displayed deficits in NORT performance with a 2 h delay between the choice and sample phases that were completely reversed by administration of darbepoetin alfa (5000 U/kg, i.p.) 1 h before the sample phase. These results suggest that darbepoetin alfa may have utility in treating memory deficits associated with brain dysfunction related to developmental disorders such as schizophrenia.

  4. Sox9 modulates cell survival and adipogenic differentiation of multipotent adult rat mesenchymal stem cells.

    PubMed

    Stöckl, Sabine; Bauer, Richard J; Bosserhoff, Anja K; Göttl, Claudia; Grifka, Joachim; Grässel, Susanne

    2013-07-01

    Sox9 is a key transcription factor in early chondrogenesis with distinct roles in differentiation processes and during embryonic development. Here, we report that Sox9 modulates cell survival and contributes to the commitment of mesenchymal stem cells (MSC) to adipogenic or osteogenic differentiation lineages. We found that the Sox9 activity level affects the expression of the key transcription factor in adipogenic differentiation, C/EBPβ, and that cyclin D1 mediates the expression of the osteogenic marker osteocalcin in undifferentiated adult bone-marrow-derived rat MSC. Introducing a stable Sox9 knockdown into undifferentiated rat MSC resulted in a marked decrease in proliferation rate and an increase in apoptotic activity. This was linked to a profound upregulation of p21 and cyclin D1 gene and protein expression accompanied by an induction of caspase 3/7 activity and an inhibition of Bcl-2. We observed that Sox9 silencing provoked a delayed S-phase progression and an increased nuclear localization of p21. The protein stability of cyclin D1 was induced in the absence of Sox9 presumably as a function of altered p38 signalling. In addition, the major transcription factor for adipogenic differentiation, C/EBPβ, was repressed after silencing Sox9. The nearly complete absence of C/EBPβ protein as a result of increased destabilization of the C/EBPβ mRNA and the impact on osteocalcin gene expression and protein synthesis, suggests that a delicate balance of Sox9 level is not only imperative for proper chondrogenic differentiation of progenitor cells, but also affects the adipogenic and probably osteogenic differentiation pathways of MSC. Our results identified Sox9 as an important link between differentiation, proliferation and apoptosis in undifferentiated adult rat mesenchymal stem cells, emphasizing the importance of the delicate balance of a precisely regulated Sox9 activity in MSC not only for proper skeletal development during embryogenesis but probably also

  5. Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

    PubMed Central

    Furuta, Miyako; Bridges, Robert S.

    2009-01-01

    The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

  6. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

    PubMed

    Yucel, Atakan; Yucel, Nermin; Ozkanlar, Seckin; Polat, Elif; Kara, Adem; Ozcan, Halil; Gulec, Mustafa

    2016-04-01

    Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

  7. Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, S. A.; Allen, M. R.; Hogan, H. A.; Delp, M. D.

    2002-01-01

    The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

  8. Daily patterns of ethanol drinking in adolescent and adult, male and female, high alcohol drinking (HAD) replicate lines of rats.

    PubMed

    Dhaher, Ronnie; McConnell, Kathleen K; Rodd, Zachary A; McBride, William J; Bell, Richard L

    2012-10-01

    The rationale for our study was to determine the pattern of ethanol drinking by the high alcohol-drinking (HAD) replicate lines of rats during adolescence and adulthood in both male and female rats. Rats were given 30 days of 24 h free-choice access to ethanol (15%, v/v) and water, with ad lib access to food, starting at the beginning of adolescence (PND 30) or adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day with a "lickometer" set-up. The results indicated that adolescent HAD-1 and HAD-2 males consumed the greatest levels of ethanol and had the most well defined ethanol licking binges among the age and sex groups with increasing levels of ethanol consumption throughout adolescence. In addition, following the first week of adolescence, male and female HAD-1 and HAD-2 rats differed in both ethanol consumption levels and ethanol licking behavior. Adult HAD-1 male and female rats did not differ from one another and their ethanol intake or licking behaviors did not change significantly over weeks. Adult HAD-2 male rats maintained a relatively constant level of ethanol consumption across weeks, whereas adult HAD-2 female rats increased ethanol consumption levels over weeks, peaking during the third week when they consumed more than their adult male counterparts. The results indicate that the HAD rat lines could be used as an effective animal model to examine the development of ethanol consumption and binge drinking in adolescent male and female rats providing information on the long-range consequences of adolescent alcohol drinking.

  9. Auto-catalytic Ceria Nanoparticles Offer Neuroprotection to Adult Rat Spinal Cord Neurons

    PubMed Central

    Das, Mainak; Patil, Swanand; Bhargava, Neelima; Kang, Jung-Fong; Riedel, Lisa M.; Seal, Sudipta; Hickman, James J.

    2007-01-01

    This paper describes the evaluation of the auto-catalytic anti-oxidant behavior and biocompatibility of Cerium oxide nanoparticles for applications in spinal cord repair and other diseases of the CNS. The application of a single dose of nano-Ceria at a nano-molar concentration is biocompatible, regenerative and provides a significant neuroprotective effect on adult rat spinal cord neurons. Retention of neuronal function is demonstrated from electrophysiological recordings and the possibility of its application to prevent ischemic insult is suggested from an oxidative injury assay. A mechanism is proposed to explain the auto-catalytic properties of these nanoparticles. PMID:17222903

  10. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection.

  11. Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model.

    PubMed

    Groves, James O; Leslie, Isla; Huang, Guo-Jen; McHugh, Stephen B; Taylor, Amy; Mott, Richard; Munafò, Marcus; Bannerman, David M; Flint, Jonathan

    2013-01-01

    The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.

  12. The Cerebellum and Premenstrual Dysphoric Disorder

    PubMed Central

    Rapkin, Andrea J.; Berman, Steven M.; London, Edythe D.

    2017-01-01

    The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

  13. Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development.

    PubMed

    Pittet, Florent; Babb, Jessica A; Carini, Lindsay; Nephew, Benjamin C

    2017-04-01

    We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

  14. Binge ethanol intoxication heightens subsequent ethanol intake in adolescent, but not adult, rats.

    PubMed

    Fabio, María Carolina; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2014-04-01

    A question still to be answered is whether ethanol initiation has a greater effect on ethanol consumption if it occurs during adolescence than in adulthood. This study assessed the effect of ethanol initiation during adolescence or adulthood on voluntary ethanol consumption when animals were still within the same age range. Adolescent or adult rats were given 5, 2, or 0 ethanol exposures. The animals were tested for ethanol consumption through two-bottle choice tests, before undergoing a 1-week deprivation. A two-bottle assessment was conducted after the deprivation. Adolescents, but not adults, given two ethanol administrations during initiation exhibited significantly higher ethanol intake during the pre-deprivation period. These adolescents also exhibited a threefold increase in ethanol intake after 7 days of drug withdrawal, when compared with controls. These findings suggest that very brief experience with binge ethanol intoxication in adolescence, but not in adulthood, impacts later predisposition to drink.

  15. The cortical response to sensory deprivation in adult rats is affected by gonadectomy.

    PubMed

    Mowery, Todd M; Elliott, Kevin S; Garraghty, Preston E

    2009-05-01

    The present study investigated the effects of adult-onset sensory deprivation and gonadectomy. Adult male and female rats underwent unilateral transection of the infraorbital nerve. Half of the subjects had been gonadectomized 1 week prior to the nerve injury. We found that the areas of deprived barrels were significantly reduced when compared to barrels in the contralateral control hemisphere, and that this shrinkage was independent of sex and gonadectomy. We also found significant reductions in cytochrome oxidase staining intensity in the deprived barrels. While there were no differences in the magnitude of this effect between males and females, this effect was substantially more pronounced in the gonadectomized subjects. That is, gonadal hormones appeared to play a significant neuroprotective role in the metabolic response of the barrel cortex to deprivation. Thus, either males and females have a common neuroprotective hormonal pathway, or each has a sex-specific hormone pathway that serves an equivalent neuroprotective function.

  16. Natural variation in maternal care shapes adult social behavior in rats.

    PubMed

    Starr-Phillips, Emily J; Beery, Annaliese K

    2014-07-01

    Features of the early postnatal environment profoundly shape later physical and behavioral phenotypes. The amount of licking/grooming that rat dams direct towards their offspring has durable consequences, including behavioral and physiological dimensions of stress reactivity, cognition, and reproductive behavior. We examined how natural variation in maternal care alters social behavior in adult offspring and how this relates to anxiety behavior and oxytocin receptor density. Male and female offspring of mothers who received high levels of licking spent significantly more time in social contact with unfamiliar individuals than did offspring whose dams provided less grooming. Reduced anxiety behavior was associated with greater social interaction. No differences in oxytocin receptor binding assessed by (125) I-OVTA autoradiography were detected between groups. The present investigation characterizes a novel impact of maternal care on adult social interaction behavior, replicates anxiety behavior differences, and illustrates connections between social behavior and anxiety in adulthood across maternal treatment groups.

  17. Eszopiclone and fluoxetine enhance the survival of newborn neurons in the adult rat hippocampus.

    PubMed

    Su, Xiaowei W; Li, Xiao-Yuan; Banasr, Mounira; Duman, Ronald S

    2009-11-01

    Clinical research has shown that co-administration of eszopiclone, a sedative-hypnotic sleeping agent, and fluoxetine, a serotonin uptake inhibitor, exerts an additive antidepressant action in treating patients with both depression and insomnia. Preclinical studies demonstrate that the behavioural actions of antidepressants are linked to neurogenesis in the adult hippocampus. To test the hypothesis that the additive effects of eszopiclone and fluoxetine could act via such a mechanism, the influence of combined administration of these agents on the proliferation and survival of bromodeoxyuridine (BrdU)-labelled newborn cells in the hippocampus of adult rats was determined. Chronic eszopiclone+fluoxetine co-administration significantly increased the survival, but not proliferation, of newborn neurons in dorsal hippocampus by approximately 50%, an effect greater than either drug alone. These findings are consistent with the hypothesis that eszopiclone enhances the antidepressant action of fluoxetine, in part via a novel mechanism that increases the survival of newborn neurons.

  18. Prenatal exposure to SKF-38393 alters the response to light of adult rats.

    PubMed

    Ferguson, S A; Kennaway, D J

    2000-05-15

    The current study examined the consequences of prenatal SKF-38393 exposure on the cellular response in the adult suprachiasmatic nuclei to light. Pregnant rats were injected with the dopamine agonist SKF-38393 or vehicle daily from gestational day 15 to 21. Adult offspring received a light pulse (1 min/2 lux) 4 or 8 h after lights off (ZT16 or ZT20 where ZT=zeitgeber time). Brains were processed for c-FOS-like immunoreactivity in the SCN. At ZT20 the number of cells expressing c-FOS protein after a light pulse was the same in both groups. At ZT16 the number of cells in the SCN of SKF-38393-exposed animals was 58% lower than the vehicle-treated group. The data suggest that prenatal SKF-38393 treatment may have long-term consequences for SCN function.

  19. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    PubMed

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  20. N-Methyl-D-Aspartate Receptor-Mediated Axonal Injury in Adult Rat Corpus Callosum

    PubMed Central

    Zhang, Jingdong; Liu, Jianuo; Fox, Howard S.; Xiong, Huangui

    2013-01-01

    Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N-methyl-D-aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input–output response. Both Glut and NMDA decreased the CAP amplitude and input–output responses, suggesting an involvement of NMDARs in Glut- and NMDA-induced axonal injury. The involvement of NMDAR in Glut-induced axonal injury was further assayed by detection of β-amyloid precursor protein (β-APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β-APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro. PMID:23161705

  1. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    PubMed

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  2. Structural changes in the adult rat auditory system induced by brief postnatal noise exposure.

    PubMed

    Ouda, Ladislav; Burianová, Jana; Balogová, Zuzana; Lu, Hui Pin; Syka, Josef

    2016-01-01

    In previous studies (Grécová et al., Eur J Neurosci 29:1921-1930, 2009; Bures et al., Eur J Neurosci 32:155-164, 2010), we demonstrated that after an early postnatal short noise exposure (8 min 125 dB, day 14) changes in the frequency tuning curves as well as changes in the coding of sound intensity are present in the inferior colliculus (IC) of adult rats. In this study, we analyze on the basis of the Golgi-Cox method the morphology of neurons in the IC, the medial geniculate body (MGB) and the auditory cortex (AC) of 3-month-old Long-Evans rats exposed to identical noise at postnatal day 14 and compare the results to littermate controls. In rats exposed to noise as pups, the mean total length of the neuronal tree was found to be larger in the external cortex and the central nucleus of the IC and in the ventral division of the MGB. In addition, the numerical density of dendritic spines was decreased on the branches of neurons in the ventral division of the MGB in noise-exposed animals. In the AC, the mean total length of the apical dendritic segments of pyramidal neurons was significantly shorter in noise-exposed rats, however, only slight differences with respect to controls were observed in the length of basal dendrites of pyramidal cells as well as in the neuronal trees of AC non-pyramidal neurons. The numerical density of dendritic spines on the branches of pyramidal AC neurons was lower in exposed rats than in controls. These findings demonstrate that early postnatal short noise exposure can induce permanent changes in the development of neurons in the central auditory system, which apparently represent morphological correlates of functional plasticity.

  3. Neonatal stress alters LTP in freely moving male and female adult rats.

    PubMed

    Kehoe, P; Bronzino, J D

    1999-01-01

    We previously reported that neonatal isolation stress significantly changes measures of hippocampal long-term potentiation (LTP) in male and female juvenile rats, i.e., at 30 days of age. The changes in dentate granule population measures, i.e., excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway, indicated that juvenile rats exposed to neonatal isolation exhibit different enhancement profiles with respect to both the magnitude and duration of LTP in a sex-specific manner. Isolated males showed a significantly greater enhancement of LTP, while female "isolates" showed significantly longer LTP duration when compared to all other groups. The present study was designed to determine whether the effects of the neonatal isolation stress paradigm endures into adulthood. Rats isolated from their mothers for 1 h per day during postnatal days 2-9 were surgically prepared at 70-90 days of age, with stimulating and recording electrodes placed in the medial perforant pathway and the hippocampal dentate gyrus, respectively. Prior to tetanization, no significant effect of sex or treatment was obtained for baseline measures of EPSP slope or PSA. In order to rule out baseline differences in hippocampal cell excitability in female adult rats, we measured the response of dentate granule cells for one estrus cycle and found no pretetanization enhancement in the evoked response in either controls or previously stressed rats. Following tetanization, there was a significant treatment and sex effect. During the induction of LTP, PSA values were significantly enhanced in both isolated males and females and had significantly longer LTP duration when compared to the unhandled control group. Additionally, we observed that females took longer to reach baseline levels than males. Taken together, these results indicate that repeated infant isolation stress enhances LTP induction and duration in both males and

  4. Sustained increase in adult neurogenesis in the rat hippocampal dentate gyrus after transient brain ischemia.

    PubMed

    Wang, Congmin; Zhang, Mingguang; Sun, Chifei; Cai, Yuqun; You, Yan; Huang, Liping; Liu, Fang

    2011-01-13

    It is known that the number of newly generated neurons is increased in the young and adult rodent subventricular zone (SVZ) and dentate gyrus (DG) after transient brain ischemia. However, it remains unclear whether increase in neurogenesis in the adult DG induced by ischemic stroke is transient or sustained. We here reported that from 2 weeks to 6 months after transient middle cerebral artery occlusion (MCAO), there were more doublecortin positive (DCX+) cells in the ipsilateral compared to the sham-control and contralateral DG of the adult rat. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected 2 days after MCAO to label newly generated cells, a large number of BrdU-labeled neuroblasts differentiated into mature granular neurons. These BrdU-labeled neurons survived for at least 6 months. When BrdU was injected 6 weeks after injury, there were still more newly generated neuroblasts differentiated into mature neurons in the ipsilateral DG. Altogether, our data indicate that transient brain ischemia initiates a prolonged increase in neurogenesis and promotes the normal development of the newly generated neurons in the adult DG.

  5. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  6. Regional development of glutamate dehydrogenase in the rat brain.

    PubMed

    Leong, S F; Clark, J B

    1984-07-01

    The development of glutamate dehydrogenase enzyme activity in rat brain regions has been followed from the late foetal stage to the adult and through to the aged (greater than 2 years) adult. In the adult brain the enzyme activity was greatest in the medulla oblongata and pons greater than midbrain = hypothalamus greater than cerebellum = striatum = cortex. In the aged adult brain, glutamate dehydrogenase activity was significantly lower in the medulla oblongata and pons when compared to the 90-day-old adult value, but not in other regions. The enzyme-specific activity of nonsynaptic (free) mitochondria purified from the medulla oblongata and pons of 90-day-old animals was about twice that of mitochondria purified from the striatum and the cortex. The specific activity of the enzyme in synaptic mitochondria purified from the above three brain regions, however, remained almost constant.

  7. Inhibition by dietary D-psicose of body fat accumulation in adult rats fed a high-sucrose diet.

    PubMed

    Ochiai, Masaru; Nakanishi, Yosuke; Yamada, Takako; Iida, Tetsuo; Matsuo, Tatsuhiro

    2013-01-01

    We investigated the anti-obesity effects of dietary D-psicose on adult rats fed a high-sucrose diet. Wistar rats (16 weeks old) that had previously been fed a high-sucrose diet (HSD) were fed HSD or a high-starch diet (HTD) with or without 5% D-psicose for 8 weeks. The food efficiency, carcass fat percentage, abdominal fat accumulation, and body weight gain were all significantly suppressed by dietary D-psicose.

  8. DOPAMINE RECEPTOR INACTIVATION IN THE CAUDATE-PUTAMEN DIFFERENTIALLY AFFECTS THE BEHAVIOR OF PREWEANLING AND ADULT RATS

    PubMed Central

    DER-GHAZARIAN, T.; GUTIERREZ, A.; VARELA, F. A.; HERBERT, M. S.; AMODEO, L. R.; CHARNTIKOV, S.; CRAWFORD, C. A.; MCDOUGALL, S. A.

    2012-01-01

    The irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been used to study the ontogeny of dopamine (DA) receptor functioning in the young and adult rat. Most notably, systemic administration of EEDQ blocks the DA agonist-induced behaviors of adult rats, while leaving the behavior of preweanling rats unaffected. The purpose of the present study was to: (a) determine whether the age-dependent actions of EEDQ involve receptors located in the dorsal caudate-putamen (CPu) and (b) confirm that EEDQ's behavioral effects result from the inactivation of DA receptors rather than some other receptor type. In Experiment 1, EEDQ or DMSO were bilaterally infused into the CPu on PD 17 or PD 84. After 24 h, rats were given bilateral microinjections of the full DA agonist R(–)-propylnorapomorphine (NPA) or vehicle into the dorsal CPu and behavior was assessed for 40 min. In Experiment 2, preweanling rats were treated as just described, except that DA receptors were protected from EEDQ-induced alkylation by administering systemic injections of D1 (SCH23390) and D2 (sulpiride) receptor antagonists. As predicted, microinjecting EEDQ into the dorsal CPu attenuated the NPA-induced locomotor activity and stereotypy of adult rats. In contrast, rats given bilateral EEDQ infusions on PD 17 exhibited a potentiated locomotor response when treated with NPA. Experiment 2 showed that DA receptor inactivation was responsible for NPA's actions. A likely explanation for these results is that EEDQ inactivates a sizable percentage of DA receptors on PD 17, but leaves the remaining receptors in a supersensitive state. This receptor supersensitivity, which probably involves alterations in G protein coupling, could account for NPA-induced locomotor potentiation. Either adult rats do not show a similar EEDQ-induced change in receptor dynamics or DA receptor inactivation was more complete in older animals and effectively eliminated the expression of DA agonist

  9. Prenatal ethanol exposure impairs temporal ordering behaviours in young adult rats.

    PubMed

    Patten, Anna R; Sawchuk, Scott; Wortman, Ryan C; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R

    2016-02-15

    Prenatal ethanol exposure (PNEE) causes significant deficits in functional (i.e., synaptic) plasticity in the dentate gyrus (DG) and cornu ammonis (CA) hippocampal sub-regions of young adult male rats. Previous research has shown that in the DG, these deficits are not apparent in age-matched PNEE females. This study aimed to expand these findings and determine if PNEE induces deficits in hippocampal-dependent behaviours in both male and female young adult rats (PND 60). The metric change behavioural test examines DG-dependent deficits by determining whether an animal can detect a metric change between two identical objects. The temporal order behavioural test is thought to rely in part on the CA sub-region of the hippocampus and determines whether an animal will spend more time exploring an object that it has not seen for a larger temporal window as compared to an object that it has seen more recently. Using the liquid diet model of FASD (where 6.6% (v/v) ethanol is provided through a liquid diet consumed ad libitum throughout the entire gestation), we found that PNEE causes a significant impairment in the temporal order task, while no deficits in the DG-dependent metric change task were observed. There were no significant differences between males and females for either task. These results indicate that behaviours relying partially on the CA-region may be more affected by PNEE than those that rely on the DG.

  10. Characterization of strychnine-sensitive glycine receptors in acutely isolated adult rat basolateral amygdala neurons.

    PubMed

    McCool, B A; Botting, S K

    2000-03-24

    Large concentrations of the beta-amino acid, taurine, can be found in many forebrain areas such as the basolateral amygdala, a portion of the limbic forebrain intimately associated with the regulation of fear/anxiety-like behaviors. In addition to its cytoprotective and osmoregulatory roles, taurine may also serve as an agonist at GABA(A)- and strychnine-sensitive glycine receptors. In this latter context, the present study demonstrates that application of taurine to acutely isolated neurons from the basolateral amygdala of adult rats causes significant alterations in resting membrane current, as measured by whole-cell patch clamp electrophysiology. Using standard pharmacological approaches, we find that currents gated by concentrations of taurine adult rats.

  11. Exposure to constant light during testis development increases daily sperm production in adult Wistar rats.

    PubMed

    Rocha, D C; Debeljuk, L; França, L R

    1999-06-01

    Testis histometry and daily sperm production (DSP) were evaluated in adult (160-day-old) Wistar rats exposed to constant light for the first 25 days after birth, and compared with control animals which were exposed to a 12 h-light-12 h-dark light regimen. Significantly greater (P < 0.05) numbers of Sertoli cell nucleoli and round spermatids per cross-section of seminiferous tubule were found in animals exposed to constant light. In addition, epididymis weight, DSP per testis and per gram of testis, as well as Leydig cell compartment volume, were significantly increased in treated animals. Although there was a clear trend toward an increased Sertoli cell population per testis in animals exposed to constant light, this difference was not statistically significant (P < 0.05). The number of round spermatids as expressed per Sertoli cell was the same in both groups. Surprisingly, the diameter and volume of round spermatid nucleus at stages I and VII of the cycle of seminiferous epithelium were significantly lower (P < 0.05) in treated animals. In conclusion, constant illumination during neonatal testis development increased sperm production and Leydig cell compartment volume in adult rats probably through a mechanism involving elevated follicle stimulating hormone and luteinizing hormone during the prepubertal period. To our knowledge, this is the first study showing that altering the light regimen can affect sperm production in non-seasonal breeders.

  12. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature.

    PubMed

    Li, Qing-Quan; Qiao, Guan-Qun; Ma, Jun; Fan, Hong-Wei; Li, Ying-Bin

    2015-02-01

    The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  13. Diazepam affects the nuclear thyroid hormone receptor density and their expression levels in adult rat brain.

    PubMed

    Constantinou, Caterina; Bolaris, Stamatis; Valcana, Theony; Margarity, Marigoula

    2005-07-01

    Thyroid hormones (THs) are involved in the occurrence of anxiety and affective disorders; however, the effects following an anxiolytic benzodiazepine treatment, such as diazepam administration, on the mechanism of action of thyroid hormones has not yet been investigated. The effect of diazepam on the in vitro nuclear T3 binding, on the relative expression of the TH receptors (TRs) and on the synaptosomal TH availability were examined in adult rat cerebral hemispheres 24 h after a single intraperitoneal dose (5 mg/kg BW) of this tranquillizer. Although, diazepam did not affect the availability of TH either in blood circulation or in the synaptosomal fraction, it decreased (33%) the nuclear T3 maximal binding density (B(max)). No differences were observed in the equilibrium dissociation constant (K(d)). The TRalpha2 variant (non-T3-binding) mRNA levels were increased by 33%, whereas no changes in the relative expression of the T3-binding isoforms of TRs (TRalpha1, TRbeta1) were observed. This study shows that a single intraperitoneal injection of diazepam affects within 24 h, the density of the nuclear TRs and their expression pattern. The latest effect occurs in an isoform-specific manner involving specifically the TRalpha2 mRNA levels in adult rat brain.

  14. Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome.

    PubMed

    Gil-Mohapel, Joana; Boehme, Fanny; Patten, Anna; Cox, Adrian; Kainer, Leah; Giles, Erica; Brocardo, Patricia S; Christie, Brian R

    2011-04-12

    Exposure to ethanol during pregnancy can be devastating to the developing nervous system, leading to significant central nervous system dysfunction. The hippocampus, one of the two brain regions where neurogenesis persists into adulthood, is particularly sensitive to the teratogenic effects of ethanol. In the present study, we tested a rat model of fetal alcohol syndrome (FAS) with ethanol administered via gavage throughout all three trimester equivalents. Subsequently, we assessed cell proliferation, as well as neuronal survival, and differentiation in the dentate gyrus of the hippocampus of adolescent (35 days old), young adult (60 days old) and adult (90 days old) Sprague-Dawley rats. Using both extrinsic (bromodeoxyuridine) and intrinsic (Ki-67) markers, we observed no significant alterations in cell proliferation and survival in ethanol-exposed animals when compared with their pair-fed and ad libitum controls. However, we detected a significant increase in the number of new immature neurons in animals that were exposed to ethanol throughout all three trimester equivalents. This result might reflect a compensatory mechanism to counteract the deleterious effects of prenatal ethanol exposure or an ethanol-induced arrest of the neurogenic process at the early neuronal maturation stages. Taken together these results indicate that exposure to ethanol during the period of brain development causes a long-lasting dysregulation of the neurogenic process, a mechanism that might contribute, at least in part, to the hippocampal deficits that have been reported in rodent models of FAS.

  15. Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus.

    PubMed

    Wong-Goodrich, Sarah J E; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2008-05-01

    Prenatal choline supplementation (SUP) protects adult rats against spatial memory deficits observed after excitotoxin-induced status epilepticus (SE). To examine the mechanism underlying this neuroprotection, we determined the effects of SUP on a variety of hippocampal markers known to change in response to SE and thought to underlie ensuing cognitive deficits. Adult offspring from rat dams that received either a control or SUP diet on embryonic days 12-17 were administered saline or kainic acid (i.p.) to induce SE and were euthanized 16 days later. SUP markedly attenuated seizure-induced hippocampal neurodegeneration, dentate cell proliferation, and hippocampal GFAP mRNA expression levels, prevented the loss of hippocampal GAD65 protein and mRNA expression, and altered growth factor expression patterns. SUP also enhanced pre-seizure hippocampal levels of BDNF, NGF, and IGF-1, which may confer a neuroprotective hippocampal microenvironment that dampens the neuropathological response to and/or helps facilitate recovery from SE to protect cognitive function.

  16. Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2016-04-21

    Methylphenidate (MPH) is a central stimulant, prescribed for the treatment of attention deficit/hyperactivity disorder. The long-term behavioral consequences of MPH treatment are unknown. In this study, the oxidative stress and neuroinflammation induced by various doses of MPH were investigated. Forty adult male rats were divided into 5 groups; and treated with different doses of MPH for 21 days. Twenty four hours after drug treatment, Open Field Test (OFT) was performed in all animals. At the end of the study, blood cortisol level (BCL) was measured and hippocampus was isolated and oxidative stress and inflammation parameters and histological changes were analyzed. Chronic MPH at all doses decreased central square entries, number of rearing, ambulation distance and time spent in central square in OFT. BCL increased in doses 10 and 20mg/kg of MPH. Furthermore, MPH in all doses markedly increased lipid peroxidation, mitochondrial oxidized glutathione (GSSG) level, Interleukin 1β (IL-1β) and Tumor Necrosis Factor α (TNF-α) in isolated hippocampus. MPH (10 and 20mg/kg) treated groups had decreased mitochondrial reduced glutathione (GSH) content, and reduced superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) activities. 10 and 20mg/kg of MPH change cell density and morphology of cells in Dentate Gyrus (DG) and CA1 areas of hippocampus. Chronic treatment with high doses of MPH can cause oxidative stress, neuroinflammation and neurodegeneration in hippocampus of adult rats.

  17. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat.

    PubMed

    Wang, Hui-Dong; Dunnavant, Floyd D; Jarman, Tabitha; Deutch, Ariel Y

    2004-07-01

    The generation of new cells in the adult mammalian brain may significantly modify pathophysiological processes in neuropsychiatric disorders. We examined the ability of chronic treatment with the antipsychotic drugs (APDs) olanzapine and haloperidol to increase the number and survival of newly generated cells in the prefrontal cortex (PFC) and striatal complex of adult male rats. Animals were treated with olanzapine or haloperidol for 3 weeks and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. Half of the animals continued on the same APD for two more weeks after BrdU challenge, with the other half receiving vehicle during this period. Olanzapine but not haloperidol significantly increased both the total number and density of BrdU-labeled cells in the PFC and dorsal striatum; no effect was observed in the nucleus accumbens. Continued olanzapine treatment after the BrdU challenge did not increase the survival of newly generated cells. The newly generated cells in the PFC did not express the neuronal marker NeuN. Despite the significant increase in newly generated cells in the PFC of olanzapine-treated rats, the total number of these cells is low, suggesting that the therapeutic effects of atypical APD treatment may not be due to the presence of newly generated cells that have migrated to the cortex.

  18. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

    PubMed

    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging.

  19. Bisphenol A exposure at an environmentally relevant dose induces meiotic abnormalities in adult male rats.

    PubMed

    Liu, Chuan; Duan, Weixia; Zhang, Lei; Xu, Shangcheng; Li, Renyan; Chen, Chunhai; He, Mindi; Lu, Yonghui; Wu, Hongjuan; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    Whether environmental exposure to bisphenol A (BPA) may induce reproductive disorders is still controversial but certain studies have reported that BPA may cause meiotic abnormalities in C. elegans and female mice. However, little is known about the effect of BPA on meiosis in adult males. To determine whether BPA exposure at an environmentally relevant dose could induce meiotic abnormalities in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 20 μg/kg body weight (bw)/day for 60 consecutive days. We found that BPA significantly increased the proportion of stage VII seminiferous epithelium and decreased the proportion of stage VIII. Consequently, spermiation was inhibited and spermatogenesis was disrupted. Further investigation revealed that BPA exposure delayed meiosis initiation in the early meiotic stage and induced the accumulation of chromosomal abnormalities and meiotic DNA double-strand breaks (DSBs) in the late meiotic stage. The latter event subsequently activated the phosphatidylinositol 3-kinase-related protein kinase (ATM). Our results suggest that long-term exposure to BPA may lead to continuous meiotic abnormalities and ultimately put mammalian reproductive health at risk.

  20. Hindlimb Stretching Alters Locomotor Function Post-Spinal Cord Injury in the Adult Rat

    PubMed Central

    Caudle, Krista L.; Atkinson, Darryn A.; Brown, Edward H.; Donaldson, Katie; Seibt, Erik; Chea, Tim; Smith, Erin; Chung, Karianne; Shum-Siu, Alice; Cron, Courtney C.; Magnuson, David S. K.

    2014-01-01

    Background Stretching is a widely accepted standard-of-care therapy following spinal cord injury that has not been systematically studied in animal models. Objective To investigate the influence of a daily stretch-based physical therapy program on locomotor recovery in adult rats with moderate T9 contusive SCI. Methods A randomized treatment and control study of stretching in an animal model of acute spinal cord injury (SCI). Moderate spinal cord injuries were delivered with the NYU Impactor. Daily stretching (30 min./day, 5 days/wk for 8 wks) was provided by a team of animal handlers. Hindlimb function was assessed using the BBB Open Field Locomotor Scale and kinematically. Passive range-of-motion for each joint was determined weekly using a goniometer. Results Declines in hindlimb function during overground stepping were observed for the first 4 weeks. BBB scores improved weeks 5–10 but remained below the control group. Stretched animals had significant deficits in knee passive ROM starting at week 4 and for the duration of the study. Kinematic assessment showed decreased joint excursion during stepping that partially recovered beginning at week 5. Conclusion Stretch-based therapy significantly impaired functional recovery in adult rats with a moderate contusive SCI at T10. The negative impact on function was greatest acutely, but persisted even after the stretching ceased at 8 weeks post-injury. PMID:25106555

  1. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

    PubMed

    Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

    2016-01-01

    Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.

  2. Maternal separation exaggerates spontaneous recovery of extinguished contextual fear in adult female rats.

    PubMed

    Xiong, Gui-Jing; Yang, Yuan; Wang, Li-Ping; Xu, Lin; Mao, Rong-Rong

    2014-08-01

    Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD.

  3. Sex mediates dopamine and adrenergic receptor expression in adult rats exposed prenatally to cocaine

    PubMed Central

    Ferris, Mark J.; Mactutus, Charles F.; Silvers, Janelle M.; Hasselrot, Ulla; Strupp, Barbara J.; Booze, Rosemarie M.

    2010-01-01

    The extent of catecholaminergic receptor and respective behavioral alterations associated with prenatal cocaine exposure varies according to exogenous factors such as the amount, frequency, and route of maternal exposure, as well as endogenous factors such as specific brain regions under consideration and sex of the species. The goal of the current study was to use autoradiography to delineate possible moderators of dopaminergic and adrenergic receptor expression in adult rat offspring exposed to cocaine in utero. The current study demonstrated sex-dependent D1 receptor, α2, and noradrenergic transporter binding alterations in prelimbic, hippocampus, and anterior cingulate regions of adult rat brains exposed to cocaine during gestational days 8–21. Of further interest was the lack of alterations in the nucleus accumbens for nearly all receptors/transporters investigated, as well as the lack of alterations in D3 receptor binding in nearly all of the regions investigated (nucleus accumbens, prelimbic region, hippocampus, and cingulate gyrus). Thus, the current investigation demonstrated persistent receptor and transporter alterations that extend well into adulthood as a result of cocaine exposure in utero. Furthermore, the demonstration that sex played a mediating role in prenatal cocaine-induced, aberrant receptor/transporter expression is of primary importance for future studies that seek to control for sex in either design or analysis. PMID:17933484

  4. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

    EPA Pesticide Factsheets

    behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil.Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP)Molecular changes induced by LTPThis dataset is associated with the following publication:Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

  5. Effects of Extremely Low Frequency Electromagnetic Fields on Vascular Permeability of Circumventricular Organs in the Adult Rat

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Mercado, Y. K.; Cañedo-Dorantes, L.; Bañuelos-Pineda, J.; Serrano-Luna, G.; Feria-Velasco, A.

    2008-08-01

    The present work deals with the effects of extremely low frequency electromagnetic fields (ELF-EMF) on blood vessels permeability to non liposoluble substances of the circumventricular organs (CVO) of adult rats. Male Wistar adult rats were exposed to ELF-EMF and vascular permeability to colloidal carbon was investigated with the use of histological techniques. Results were compared to corresponding data from sham-exposed and control groups of animals. Exposure to ELF-EMF increased the CVO vascular permeability to colloidal carbon intravascularly injected, particularly in the subfornical organ, the median eminence, the pineal gland and the area postrema.

  6. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

    PubMed

    Greisen, Mia H; Altar, C Anthony; Bolwig, Tom G; Whitehead, Richard; Wörtwein, Gitta

    2005-03-15

    Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

  7. IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats

    PubMed Central

    Pang, Yi; Bhatt, Abhay J.; Fan, Lir-Wan

    2015-01-01

    We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an antiinflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist. PMID:25665855

  8. IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats.

    PubMed

    Lan, Kuo-Mao; Tien, Lu-Tai; Pang, Yi; Bhatt, Abhay J; Fan, Lir-Wan

    2015-04-02

    We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist.

  9. Consensus Paper: The Cerebellum's Role in Movement and Cognition

    PubMed Central

    Koziol, Leonard F.; Budding, Deborah; Andreasen, Nancy; D'Arrigo, Stefano; Bulgheroni, Sara; Imamizu, Hiroshi; Ito, Masao; Manto, Mario; Marvel, Cherie; Parker, Krystal; Pezzulo, Giovanni; Ramnani, Narender; Riva, Daria; Schmahmann, Jeremy; Vandervert, Larry; Yamazaki, Tadashi

    2014-01-01

    While the cerebellum's role in motor function is well recognized, the nature of its concurrent role in cognitive function remains considerably less clear. The current consensus paper gathers diverse views on a variety of important roles played by the cerebellum across a range of cognitive and emotional functions. This paper considers the cerebellum in relation to neurocognitive development, language function, working memory, executive function, and the development of cerebellar internal control models and reflects upon some of the ways in which better understanding the cerebellum's status as a “supervised learning machine” can enrich our ability to understand human function and adaptation. As all contributors agree that the cerebellum plays a role in cognition, there is also an agreement that this conclusion remains highly inferential. Many conclusions about the role of the cerebellum in cognition originate from applying known information about cerebellar contributions to the coordination and quality of movement. These inferences are based on the uniformity of the cerebellum's compositional infrastructure and its apparent modular organization. There is considerable support for this view, based upon observations of patients with pathology