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Sample records for adult rats increased

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.

    PubMed

    Fan, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Xue, Jing-Ling; Wang, Fei-Fei; Zhang, Li; Yan, You-E

    2016-11-01

    The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.

  10. 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.

  11. 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.

  12. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    PubMed

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  13. Mild eccentric exercise increases Hsp72 content in skeletal muscles from adult and late middle-aged rats.

    PubMed

    Lewis, Evan J H; Ramsook, Andrew H; Locke, Marius; Amara, Catherine E

    2013-09-01

    The loss of muscle mass with age or sarcopenia contributes to increased morbidity and mortality. Thus, preventing muscle loss with age is important for maintaining health. Hsp72, the inducible member of the Hsp70 family, is known to provide protection to skeletal muscle and can be increased by exercise. However, ability to increase Hsp72 by exercise is intensity-dependent and appears to diminish with advanced age. Thus, other exercise modalities capable of increasing HSP content and potentially preventing the age related loss of muscle need to be explored. The purpose of this study was to determine if the stress from one bout of mild eccentric exercise was sufficient to elicit an increase in Hsp72 content in the vastus intermedius (VI) and white gastrocnemius (WG) muscles, and if the Hsp72 response differed between adult and late middle-aged rats. To do this, 30 adult (6 months) and late middle-aged (24 months) F344BN rats were randomly divided into three groups (n = 6/group): control (C), level exercise (16 m x min(-1)) and eccentric exercise (16 m x min(-1), 16 degree decline). Exercised animals were sacrificed immediately post-exercise or after 48 hours. Hematoxylin and Eosin staining was used to assess muscle damage, while Western Blotting was used to measure muscle Hsp72 content. A nested ANOVA with Tukey post hoc analysis was performed to determine significant difference (p < 0.05) between groups. Hsp72 content was increased in the VI for both adult and late middle-aged rats 48 hours after eccentric exercise when compared to level and control groups but no differences between age groups was observed. Hsp72 was not detected in the WG following any type of exercise. In conclusion, mild eccentric exercise can increase Hsp72 content in the rat VI muscle and this response is maintained into late middle-age.

  14. Food deprivation increases alpha(2)-adrenoceptor-mediated modulation of jejunal epithelial transport in young and adult rats.

    PubMed

    Lucas-Teixeira, V; Vieira-Coelho, M A; Serrão, M P; Soares-da-Silva, P

    2000-10-01

    This study examined the effect of food deprivation on the jejunal response to alpha(2)-adrenoceptor activation in young (20-d-old) and adult (60-d-old) rats, using short-circuit (I(sc)) measurements in the absence or presence of furosemide (1 mmol/L). The effect of alpha(2)-adrenoceptor stimulation by 5-bromo-N:-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304; 0.3-3000 nmol/L) was a concentration-dependent decrease in I(sc) with similar half-maximal effective concentration (EC(50); 12.3 +/- 1.1 vs. 9.6 +/- 1.1 nmol/L) and maximal effect (E(max); 70.6 +/- 6.9 vs. 80.6 +/- 4.5% of reduction) values in adult food-deprived and fed rats. The effect of UK 14,304 on I(sc) in fed and food-deprived rats was markedly (P: < 0.05) attenuated by furosemide (1 mmol/L). E(max) values for UK 14,304 in 20-d-old food-deprived rats were higher (P: < 0.05) than those observed in fed rats (93.3 +/- 3.3 vs. 67.0 +/- 11.3% of reduction), without differences in EC(50) values. The effect of UK 14,304 on I(sc) in 20-d-old fed rats was completely abolished by furosemide (1 mmol/L). In food-deprived young rats, the effect of UK 14,304 was also markedly (P: < 0.05) antagonized by furosemide, but not completely abolished. Specific [(3)H]-rauwolscine binding in membranes from jejunal epithelial cells revealed the presence of a single class of binding sites, with an apparent K:(D) in the low nmol/L range. In 20-d-old food-deprived rats, specific [(3)H]-rauwolscine binding was markedly increased, and this was reversed by refeeding. Na(+),K(+)-ATPase activity in isolated jejunal epithelial cells from 60-d-old fed rats was twice that in 20-d-old fed rats [117 +/- 14 vs. 52 +/- 5 nmol free inorganic phosphorus/(mg protein.min)]. Food deprivation in adult rats, but not in 20-d-old rats, was accompanied by a significant decrease in Na(+),K(+)-ATPase activity. In both young and adult rats (fed and food-deprived), UK 14,304 did not affect Na(+),K(+)-ATPase activity. In conclusion, food

  15. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  16. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  17. Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus

    PubMed Central

    Skucas, Vanessa A.; Duffy, Aine M.; Harte-Hargrove, Lauren; Magagna-Poveda, Alejandra; Radman, Thomas; Chakraborty, Goutam; Schroeder, Charles E.; MacLusky, Neil J.; Scharfman, H.E.

    2013-01-01

    Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation (LTP) of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms, and found that Gdx induced a long-lasting upregulation of MF brain-derived neurotrophic factor (BDNF) immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins such as BDNF, reversed the increase in MF transmission, excitability and LTP in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metabolites dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol were examined. Exposure of slices to 50 nM DHT decreased the effects of Gdx on MF transmission but 50 nM 5α-androstane-3α,17β-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that androgens may normally be important in area CA3 to prevent hyperexcitability and aberrant axon outgrowth, but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity. PMID:23392664

  18. Neonatal nicotine exposure increases excitatory synaptic transmission and attenuates nicotine-stimulated GABA release in the adult rat hippocampus.

    PubMed

    Damborsky, Joanne C; Griffith, William H; Winzer-Serhan, Ursula H

    2015-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1-7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking.

  19. Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats.

    PubMed

    Tian, XiaoYan; Setterberg, Rebecca B; Li, Xiaodong; Paszty, Chris; Ke, Hua Zhu; Jee, Webster S S

    2010-09-01

    The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague-Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites.

  20. Caloric restriction increases internal iliac artery and penil nitric oxide synthase expression in rat: comparison of aged and adult rats.

    PubMed

    Ozbek, Emin; Simsek, Abdulmuttalip; Ozbek, Mustafa; Somay, Adnan

    2013-09-26

    Because of the positive corelation between healthy cardiovascular system and sexual life we aimed to evaluate the effect of caloric restriction (CR) on endothelial and neuronal nitric oxide synthase (eNOS, nNOS) expression in cavernousal tissues and eNOS expression in the internal iliac artery in young and aged rats. Young (3 mo, n = 7) and aged (24 mo, n = 7) male Sprague-Dawley rats were subjected to 40% CR and were allowed free access to water for 3 months. Control rats (n = 14) fed ad libitum had free access to food and water at all times. On day 90, rats were sacrificed and internal iliac arteries and penis were removed and parafinized, eNOS and nNOS expression evaluated with immunohistochemistry. Results were evaluated semiquantitatively. eNOS and nNOS expression in cavernousal tis- sue in CR rats were more strong than in control group in both young and old rats. eNOS expression was also higher in the internal iliac arteries of CR rats than in control in young and old rats. As a result of our study we can say that there is a positive link between CR and neurotransmitter of erection in cavernousal tissues and internal iliac arteries. CR has beneficial effect to prevent sexual dysfunction in young and old animals and possible humans.

  1. Early enriched environment induces an increased conversion of proBDNF to BDNF in the adult rat's hippocampus.

    PubMed

    Cao, Wenyu; Duan, Juan; Wang, Xueqin; Zhong, Xiaolin; Hu, Zhaolan; Huang, Fulian; Wang, Hongtao; Zhang, Juan; Li, Fang; Zhang, Jianyi; Luo, Xuegang; Li, Chang-Qi

    2014-05-15

    An enriched environment has been shown to influence brain plasticity and function by involving the action of brain-derived neurotrophic factor (BDNF). BDNF, which is synthesized as a precursor molecule (proBDNF) that undergoes proteolytic cleavage, plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behavior. The neurotrophins and proneurotrophins often play opposite roles in the brain, suggesting that proteolytic cleavage of proneurotrophins controls the action of neurotrophins. However, few studies have focused on the expression and cleavage of proBDNF after exposure to an enriched environment. Our study aimed to explore the effects of an early-enriched environment on the conversion of proBDNF to BDNF in the adult rats' hippocampus. We found that there was no difference in the expression of proBDNF in the hippocampus between the SE (standard environment) and EE (enriched environment) rats, but a significantly increased BDNF protein level was found in the EE rats. Thus, a remarkably enhanced ratio of BDNF to proBDNF (BDNF/proBDNF) was observed in the EE rats. In addition, the EE resulted in a remarkably up-regulated matrix metalloproteinase-9 (MMP-9) in the hippocampus, which played a key role in converting proBDNF to BDNF in the extracellular space. Furthermore, the expression of synapse-related proteins (NR1 and NR2A) was analyzed, and the results indicated that EE could significantly increase the expression of NR1 and NR2A in the hippocampus. In addition, the behavioral results showed that EE reduced anxiety-like behavior in the elevated-plus maze test and reduced immobility time in the forced swimming test. Moreover, the EE resulted in an increased preference for sucrose compared to the SE. These results suggested that the EE up-regulated MMP-9 levels within the hippocampus, which might facilitate the conversion of proBDNF to BDNF, thereby contributing to the long lasting alterations of

  2. Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of ΔFosB in the Nucleus Accumbens

    PubMed Central

    Carneiro de Oliveira, Paulo E.; Leão, Rodrigo M.; Bianchi, Paula C.; Marin, Marcelo T.; Planeta, Cleopatra da Silva; Cruz, Fábio C.

    2016-01-01

    While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. PMID:27672362

  3. Ischemia Increases the Twitch Latent Period in the Soleus and Extensor Carpi Radialis Longus Muscles from Adult Rats.

    PubMed

    Morales, Camilo; Fierro, Leonardo

    2016-10-27

    Complete ischemia and reperfusion effects on twitch force (∫(F·t)), twitch latent period (TLP), maximal rate of rise of twitch tension (δF/δt)max, and twitch maximum relaxation rate (TMRR) were assessed. We divided 36 adult rats into four groups; two control groups (n = 9), a group undergoing 1 hour of ischemia followed by 1 hour of reperfusion (n = 9), and one group exposed to 2 hours of ischemia followed by 1 hour of reperfusion (n = 9). We have induced twitch contractions every 10 minutes in the soleus and the extensor carpi radialis longus (ECRL). Twitch contractions were recorded and then analyzed for ∫(F·t), TLP, (δF/δt)max, and TMRR. During 1 hour and 40 minutes of ischemia, TLP increased to 179 ± 24% (p < 0.05) in the soleus and to 184 ± 16% (p < 0.05) in the ECRL, an effect that was partially recovered during 1 hour of reperfusion. This increase started after 20 minutes of ischemia in the soleus and after 40 minutes of ischemia in the ECRL. The increase was faster in the ECRL and peaked at the same time for both muscular groups. ∫(F·t) and (δF/δt)max decreased during 1 hour of ischemia to 46 ± 7% (p < 0.05) in the soleus and to 40 ± 7% (p < 0.05) in the ECRL. TMRR decreased during 1 hour of ischemia to 39 ± 5% (p < 0.05) in the soleus and to 54 ± 8% (p < 0.05) in the ECRL. During 1 hour of reperfusion all of them recovered close to control values.

  4. Chronic neonatal nicotine exposure increases excitation in the young adult rat hippocampus in a sex-dependent manner

    PubMed Central

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2012-01-01

    Smoking during pregnancy exposes the fetus to nicotine, resulting in nicotine-stimulated neurotransmitter release. Recent evidence suggests that the hippocampus develops differently in males and females with delayed maturation in males. We show that chronic nicotine exposure during the first postnatal week has sex-specific long-term effects. Neonatal rat pups were chronically treated with nicotine (6 mg/kg/day) (CNN) from postnatal day 1 to 7 or milk only (Controls), and hippocampal slices were prepared from Control- and CNN-treated young adults. Field excitatory postsynaptic potentials (fEPSPs) or population spikes (PSs) were recorded from the CA1 hippocampus following CA1 s. radiatum stimulation. Input/Output curves constructed from fEPSP data indicated that CNN-males, but not females, had significantly increased excitatory responses compared to Controls (p<0.05, n=10 Con, n=11 CNN). Long-term potentiation (LTP) was not significantly changed by CNN. In the presence of bicuculline, which blocks inhibitory GABAA receptors, an epileptiform burst consisting of a series of PSs was evoked. The amplitude of the first PS was significantly larger in CNN-males and females compared to Controls (males: p<0.01, n=8 Con, n=8 CNN; females: p<0.05, n=9 Con, n=7 CNN). Only CNN-males also had significantly larger second PSs (p<0.05, n=8 con, n=8 CNN). Epileptiform activity evoked by zero Mg2+ incubation did not differ in amplitude or duration of bursts in CNN-males or females compared to Controls. These data indicate that neonatal nicotine exposure has long lasting effects and results in increased excitation within the CA1 hippocampus in adulthood, with males showing increased sensitivity to nicotine's effects. PMID:22119395

  5. Early social isolation disrupts latent inhibition and increases dopamine D2 receptor expression in the medial prefrontal cortex and nucleus accumbens of adult rats.

    PubMed

    Han, Xiao; Li, Nanxin; Xue, Xiaofang; Shao, Feng; Wang, Weiwen

    2012-04-04

    Adolescence is a critical period for neurodevelopment. In the present study, we investigated the effects of peri-adolescent social isolation on latent inhibition (LI) and dopamine D2 receptor expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) of young adult rats. Male Sprague-Dawley rats were randomly divided into adolescent isolation (ISO; isolated housing, 21-34 days of age) and social housing (SOC) groups. LI was tested at postnatal day 56. After behavioral testing, the number of dopamine D2 receptor-expressing cells was determined using immunohistochemistry. Adolescent social isolation impaired LI and increased the number of cells expressing the D2 receptor in the mPFC and NAc. The results suggest that adolescent social isolation produces profound effects on cognitive and dopaminergic function in adult rats, and could be used as an animal model of various neurodevelopmental disorders.

  6. Spinal dorsal horn cell receptive field size is increased in adult rats following neonatal hindpaw skin injury.

    PubMed

    Torsney, Carole; Fitzgerald, Maria

    2003-07-01

    Local tissue damage in newborn rats can lead to changes in skin sensitivity that last into adulthood and this is likely to be due to plasticity of developing peripheral and central sensory connections. This study examines the functional connections of dorsal horn neurons in young and adult rats that have undergone local skin damage at birth. Newborn rat pups were halothane anaesthetised and received either a unilateral subcutaneous plantar injection of 1 % lambda-carrageenan or a unilateral plantar foot injury made by removal of 2 mm x 2 mm of skin. At 3 weeks, (postnatal day (P) 19-23) and 6 weeks (P40-44) in vivo extracellular recordings of single dorsal horn cells with plantar cutaneous receptive fields were made under urethane anaesthesia (2 g kg-1) and responses to mechanical and electrical stimulation of the skin were assessed. Following neonatal carrageenan inflammation, dorsal horn neuron properties and receptive field sizes at 3 weeks were the same as those of controls. In contrast, following neonatal skin injury, dorsal horn cell receptive field sizes were significantly greater than those of controls at 3 weeks (2.5-fold) and at 6 weeks (2.2-fold). Mechanical thresholds, mechanical response magnitudes and evoked responses to single and repeated A and C fibre stimulation remained unaffected. These results show that early skin injury can cause prolonged changes in central sensory connections that persist into adult life, long after the skin has healed. Enlarged dorsal horn neuron receptive field sizes provide a physiological mechanism for the persistent behavioural hypersensitivity that follows neonatal skin injury in rats and for the prolonged sensory changes reported in human infants after early pain and injury.

  7. Intrauterine metabolic programming alteration increased susceptibility to non-alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring.

    PubMed

    Wang, Linlong; Shen, Lang; Ping, Jie; Zhang, Li; Liu, Zhongfen; Wu, Yong; Liu, Yansong; Huang, Hegui; Chen, Liaobin; Wang, Hui

    2014-01-30

    An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD.

  8. Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats.

    PubMed

    Stopponi, Serena; Soverchia, Laura; Ubaldi, Massimo; Cippitelli, Andrea; Serpelloni, Giovanni; Ciccocioppo, Roberto

    2014-07-01

    Cannabis derivatives are among the most widely used illicit substances among young people. The addictive potential of delta-9-tetrahydrocannabinol (THC), the major active ingredient of cannabis is well documented in scientific literature. However, the consequence of THC exposure during adolescence on occurrence of addiction for other drugs of abuse later in life is still controversial. To explore this aspect of THC pharmacology, in the present study, we treated adolescent rats from postnatal day (PND) 35 to PND-46 with increasing daily doses of THC (2.5-10mg/kg). One week after intoxication, the rats were tested for anxiety-like behavior in the elevated plus maze (EPM) test. One month later (starting from PND 75), rats were trained to operantly self-administer heroin intravenously. Finally, following extinction phase, reinstatement of lever pressing elicited by the pharmacological stressor, yohimbine (1.25mg/kg) was evaluated. Data revealed that in comparison to controls, animals treated with chronic THC during adolescence showed a higher level of anxiety-like behavior. When tested for heroin (20μg per infusion) self-administration, no significant differences were observed in both the acquisition of operant responding and heroin intake at baseline. Noteworthy, following the extinction phase, administration of yohimbine elicited a significantly higher level of heroin seeking in rats previously exposed to THC. Altogether these findings demonstrate that chronic exposure to THC during adolescence is responsible for heightened anxiety and increased vulnerability to drug relapse in adulthood.

  9. Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens.

    PubMed

    Alaux-Cantin, Stéphanie; Warnault, Vincent; Legastelois, Rémi; Botia, Béatrice; Pierrefiche, Olivier; Vilpoux, Catherine; Naassila, Mickaël

    2013-04-01

    Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism. However, mechanisms underlying this susceptibility remain unknown. We evaluated the effect of adolescent binge-like ethanol intoxication on vulnerability to alcohol abuse in Sprague-Dawley rats. To model binge-like ethanol intoxication, every 2 days, rats received an ethanol injection (3.0 g/kg) for 2 consecutive days across 14 days either from postnatal day 30 (PND30) to 43 (early adolescence) or from PND 45 to PND 58 (late adolescence). In young adult animals, we measured free ethanol consumption in the two-bottle choice paradigm, motivation for ethanol in the operant self-administration task and both ethanol's rewarding and aversive properties in the conditioned place preference (CPP) and taste aversion (CTA) paradigms. While intermittent ethanol intoxications (IEI) during late adolescence had no effect on free-choice 10% ethanol consumption, we found that IEI during early adolescence promoted free-choice 10% ethanol consumption, enhanced motivation for ethanol in the self-administration paradigm and induced a loss of both ethanol-induced CPP and CTA in young adults. No modification in either sucrose self-administration or amphetamine-induced CPP was observed. As the nucleus accumbens (Nac) is particularly involved in addictive behavior, we analyzed IEI-induced long-term neuroadaptations in the Nac using c-Fos immunohistochemistry and an array of neurotransmission-related genes. This vulnerability to ethanol abuse was associated with a lower c-Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission-related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism.

  10. Chronic ethanol exposure increases voluntary home cage intake in adult male, but not female, Long-Evans rats.

    PubMed

    Morales, Melissa; McGinnis, Molly M; McCool, Brian A

    2015-12-01

    The current experiment examined the effects of 10 days of chronic intermittent ethanol (CIE) exposure on anxiety-like behavior and home cage ethanol intake using a 20% intermittent access (M, W, F) paradigm in male and female Long-Evans rats. Withdrawal from alcohol dependence contributes to relapse in humans and increases in anxiety-like behavior and voluntary ethanol consumption in preclinical models. Our laboratory has shown that 10 days of CIE exposure produces both behavioral and neurophysiological alterations associated with withdrawal in male rats; however, we have yet to examine the effects of this exposure regime on ethanol intake in females. During baseline, females consumed more ethanol than males but, unlike males, did not show escalations in intake. Rats were then exposed to CIE and were again given intermittent access to 20% ethanol. CIE males increased their intake compared to baseline, whereas air-exposed males did not. Ethanol intake in females was unaffected by CIE exposure. Notably, both sexes expressed significantly elevated withdrawal-associated anxiety-like behavior in the plus maze. Finally, rats were injected with the cannabinoid CB1 receptor antagonist, SR141716A (0, 1, 3, 10mg/kg, i.p.) which reduced ethanol intake in both sexes. However, females appear to be more sensitive to lower doses of this CB1 receptor antagonist. Our results show that females consume more ethanol than males; however, they did not escalate their intake using the intermittent access paradigm. Unlike males, CIE exposure had no effect on drinking in females. It is possible that females may be less sensitive than males to ethanol-induced increases in drinking after a short CIE exposure. Lastly, our results demonstrate that males and females may have different pharmacological sensitivities to CB1 receptor blockade on ethanol intake, at least under the current conditions.

  11. Adolescent exposure to cocaine increases anxiety-like behavior and induces morphologic and neurochemical changes in the hippocampus of adult rats.

    PubMed

    Zhu, W; Mao, Z; Zhu, C; Li, M; Cao, C; Guan, Y; Yuan, J; Xie, G; Guan, X

    2016-01-28

    Repeated exposure to cocaine during adolescence may affect both physical and psychological conditions in the brain, and increase the risk of psychiatric disorders and addiction behaviors in adulthood. Adolescence represents a critical development period for the hippocampus. Moreover, different regions of the hippocampus are involved in different functions. Dorsal hippocampus (dHP) has been implicated in learning and memory, whereas ventral hippocampus (vHP) plays an important role in emotional processing. In this study, the rats that were exposed to cocaine during adolescence (postnatal days, P28-P42) showed higher anxiety-like behavior in the elevated plus maze test in adulthood (P80), but displayed normal spatial learning and memory in the Morris water maze test. Furthermore, repeated exposure to cocaine during adolescence lead to alterations in morphology of pyramidal neurons, activities of astrocytes, and levels of proteins that involved in synaptic transmission, apoptosis, inflammation and addiction in both dHP and vHP of adult rats. These findings suggest that repeated exposure to cocaine during adolescence in rats may elicit morphologic and neurochemical changes in the hippocampus when the animals reach adulthood. These changes may contribute to the increased susceptibility for psychiatric disorders and addiction seen in adults.

  12. Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats.

    PubMed

    Hamson, D K; Wainwright, S R; Taylor, J R; Jones, B A; Watson, N V; Galea, L A M

    2013-09-01

    Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.

  13. Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat.

    PubMed

    Zhang, X-L; Albers, K M; Gold, M S

    2015-01-22

    The goals of the present study were to determine (1) the properties of the nicotinic acetylcholine receptor (nAChR) currents in rat cutaneous dorsal root ganglion (DRG) neurons; (2) the impact of nAChR activation on the excitability of cutaneous DRG neurons; and (3) the impact of inflammation on the density and distribution of nAChR currents among cutaneous DRG neurons. Whole-cell patch-clamp techniques were used to study retrogradely labeled DRG neurons from naïve and complete Freund's adjuvant inflamed rats. Nicotine-evoked currents were detectable in ∼70% of the cutaneous DRG neurons, where only one of two current types, fast or slow currents based on rates of activation and inactivation, was present in each neuron. The biophysical and pharmacological properties of the fast current were consistent with nAChRs containing an α7 subunit while those of the slow current were consistent with nAChRs containing α3/β4 subunits. The majority of small diameter neurons with fast current were IB4- while the majority of small diameter neurons with slow current were IB4+. Preincubation with nicotine (1 μM) produced a transient (1 min) depolarization and increase in the excitability of neurons with fast current and a decrease in the amplitude of capsaicin-evoked current in neurons with slow current. Inflammation increased the current density of both slow and fast currents in small diameter neurons and increased the percentage of neurons with the fast current. With the relatively selective distribution of nAChR currents in putative nociceptive cutaneous DRG neurons, our results suggest that the role of these receptors in inflammatory hyperalgesia is likely to be complex and dependent on the concentration and timing of acetylcholine release in the periphery.

  14. Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

    PubMed Central

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J.; Poston, Lucilla; Taylor, Paul D.

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID:22043281

  15. Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression?

    PubMed

    Hansen, H H; Sánchez, C; Meier, E

    1997-12-01

    Chronic administration of the tricyclic antidepressant clomipramine to neonatal rats from postnatal days 8 to 21 is reported to induce several behavioral changes in adult life, and it may serve as an animal model of human depressive disorder. Findings include increased immobility time in the forced swim test and locomotor hyperactivity in the open field test. Clomipramine is a serotonergic reuptake inhibitor, which suggests that altered development of the serotonergic system could account for the observed behavioral changes in the adult rat. The present study was carried out with a selective serotonin reuptake inhibitor (SSRI) to investigate whether the serotonin system, in particular, is involved in the neonatal animal model. The substance, Lu 10-134-C (LU), was characterized in monoamine reuptake and receptor binding assays and found to be an SSRI. Rats received LU during postnatal days 8 to 21 (2.5-15 mg/kg b. i.d.), and they were assessed in open field, forced swim and social interaction tests at the age of 4 months. Behavior of LU-treated rats and saline controls did not differ in the open field and social interaction tests. However, in the forced swim tests LU-treated neonates showed prolonged immobility time compared with saline controls. In conclusion, chronic LU treatment during neonatal life produces long-term changes in the forced swim test, but not in the open field and social interaction tests. The behavioral changes in the forced swim test suggest that the central serotonergic system may be involved in the putative neonatal animal model of depression.

  16. Administration of anabolic steroid during adolescence induces long-term cardiac hypertrophy and increases susceptibility to ischemia/reperfusion injury in adult Wistar rats.

    PubMed

    Cruz Seara, Fernando de Azevedo; Barbosa, Raiana Andrade Quintanilha; Oliveira, Dahienne Ferreira de; Silva, Diorney Luiz Souza Gran da; Carvalho, Adriana Bastos; Ferreira, Andrea Claudia Freitas; Nascimento, José Hamilton Matheus; Olivares, Emerson Lopes

    2017-02-05

    Chronic administration of anabolic androgenic steroids (AAS) in adult rats results in cardiac hypertrophy and increased susceptibility to myocardial ischemia/reperfusion (IR) injury. Molecular analyses demonstrated that hyperactivation of type 1 angiotensin II (AT1) receptor mediates cardiac hypertrophy induced by AAS and also induces down-regulation of myocardial ATP-sensitive potassium channel (KATP), resulting in loss of exercise-induced cardioprotection. Exposure to AAS during adolescence promoted long-term cardiovascular dysfunctions, such as dysautonomia. We tested the hypothesis that chronic AAS exposure in the pre/pubertal phase increases the susceptibility to myocardial ischemia/reperfusion (IR) injury in adult rats. Male Wistar rats (26day old) were treated with vehicle (Control, n=12) or testosterone propionate (TP) (AAS, 5mgkg(-1) n=12) 5 times/week during 5 weeks. At the end of AAS exposure, rats underwent 23days of washout period and were submitted to euthanasia. Langendorff-perfused hearts were submitted to IR injury and evaluated for mechanical dysfunctions and infarct size. Molecular analysis was performed by mRNA levels of α-myosin heavy chain (MHC), βMHC and brain-derived natriuretic peptide (BNP), ryanodine receptor (RyR2) and sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) by quantitative RT-PCR (qRT-PCR). The expression of AT1 receptor and KATP channel subunits (Kir6.1 and SURa) was analyzed by qRT-PCR and Western Blot. NADPH oxidase (Nox)-related reactive oxygen species generation was assessed by spectrofluorimetry. The expression of antioxidant enzymes was measured by qRT-PCR in order to address a potential role of redox unbalance. AAS exposure promoted long-term cardiac hypertrophy characterized by increased expression of βMHC and βMHC/αMHC ratio. Baseline derivative of pressure (dP/dt) was impaired by AAS exposure. Postischemic recovery of mechanical properties was impaired (decreased left ventricle [LV] developed pressure and

  17. The NMDA receptor antagonist MK-801 abolishes the increase in both p53 and Bax/Bcl2 index induced by adult-onset hypothyroidism in rat.

    PubMed

    Alva-Sanchez, Claudia; Rodriguez, Adair; Villanueva, Ivan; Anguiano, Brenda; Aceves, Carmen; Pacheco-Rosado, Jorge

    2014-01-01

    Hypothyroidism affects neuron population dynamics in the hippocampus of the adult rat, with neuronal damage as the main feature of its effect. This effect is prevented by the blockade of NMDA receptors, which suggests that glutamatergic activity mediates cell death in this condition. Glutamate can also stimulate cell proliferation and survival of newborn neurons, indicating that it can affect different stages of the cell cycle. In this work we measured the expression of specific proteins that control cell proliferation (cycline-D1), cell arrest (p21), damage (p53) or apoptosis (Bax and Bcl2) in the hippocampus of hypothyroid rats treated with the NMDA receptor (NMDAR) blocker MK-801 during the induction of hypothyroidism. The results show that hypothyroidism increases the expression of markers of DNA damage, cell arrest, and apoptosis, but does not affect the marker of cell proliferation. NMDAR blockade prevents the increase on markers of DNA damage and apoptosis, but does not influence cell arrest or cell proliferation. This suggests that hypothyroidism promotes cell death mainly by an excitotoxic effect of glutamate.

  18. Endogenous BDNF protein is increased in adult rat hippocampus after a kainic acid induced excitotoxic insult but exogenous BDNF is not neuroprotective.

    PubMed

    Rudge, J S; Mather, P E; Pasnikowski, E M; Cai, N; Corcoran, T; Acheson, A; Anderson, K; Lindsay, R M; Wiegand, S J

    1998-02-01

    Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.

  19. Maternal hypoxia increases the susceptibility of adult rat male offspring to high-fat diet-induced nonalcoholic fatty liver disease.

    PubMed

    Su, Yi-Ming; Lv, Guo-Rong; Xie, Jing-Xian; Wang, Zhen-Hua; Lin, Hui-Tong

    2013-11-01

    Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.

  20. Cytidine-5-diphosphocholine supplement in early life induces stable increase in dendritic complexity of neurons in the somatosensory cortex of adult rats

    PubMed Central

    Rema, V.; Bali, K.K.; Ramachandra, R.; Chugh, M.; Darokhan, Z.; Chaudhary, R.

    2008-01-01

    Cytidine-5-diphosphocholine (CDP-choline or citicholine) is an essential molecule that is required for biosynthesis of cell membranes. In adult humans it is used as a memory-enhancing drug for treatment of age-related dementia and cerebrovascular conditions. However the effect of CDP-choline on perinatal brain is not known. We administered CDP-choline to Long Evans rats each day from conception (maternal ingestion) to postnatal day 60 (P60). Pyramidal neurons from supragranular layers 2/3, granular layer 4 and infragranular layer 5 of somatosensory cortex were examined with Golgi–Cox staining at P240. CDP-choline treatment significantly increased length and branch points of apical and basal dendrites. Sholl analysis shows that the complexity of apical and basal dendrites of neurons is maximal in layers 2/3 and layer 5. In layer 4 significant increases were seen in basilar dendritic arborization. CDP-choline did not increase the number of primary basal dendrites on neurons in the somatosensory cortex. Primary cultures from somatosensory cortex were treated with CDP-choline to test its effect on neuronal survival. CDP-choline treatment neither enhanced the survival of neurons in culture nor increased the number of neurites. However significant increases in neurite length, branch points and total area occupied by the neurons were observed. We conclude that exogenous supplementation of CDP-choline during development causes stable changes in neuronal morphology. Significant increase in dendritic growth and branching of pyramidal neurons from the somatosensory cortex resulted in enlarging the surface area occupied by the neurons which we speculate will augment processing of sensory information. PMID:18619738

  1. Cytidine-5-diphosphocholine supplement in early life induces stable increase in dendritic complexity of neurons in the somatosensory cortex of adult rats.

    PubMed

    Rema, V; Bali, K K; Ramachandra, R; Chugh, M; Darokhan, Z; Chaudhary, R

    2008-08-13

    Cytidine-5-diphosphocholine (CDP-choline or citicholine) is an essential molecule that is required for biosynthesis of cell membranes. In adult humans it is used as a memory-enhancing drug for treatment of age-related dementia and cerebrovascular conditions. However the effect of CDP-choline on perinatal brain is not known. We administered CDP-choline to Long Evans rats each day from conception (maternal ingestion) to postnatal day 60 (P60). Pyramidal neurons from supragranular layers 2/3, granular layer 4 and infragranular layer 5 of somatosensory cortex were examined with Golgi-Cox staining at P240. CDP-choline treatment significantly increased length and branch points of apical and basal dendrites. Sholl analysis shows that the complexity of apical and basal dendrites of neurons is maximal in layers 2/3 and layer 5. In layer 4 significant increases were seen in basilar dendritic arborization. CDP-choline did not increase the number of primary basal dendrites on neurons in the somatosensory cortex. Primary cultures from somatosensory cortex were treated with CDP-choline to test its effect on neuronal survival. CDP-choline treatment neither enhanced the survival of neurons in culture nor increased the number of neurites. However significant increases in neurite length, branch points and total area occupied by the neurons were observed. We conclude that exogenous supplementation of CDP-choline during development causes stable changes in neuronal morphology. Significant increase in dendritic growth and branching of pyramidal neurons from the somatosensory cortex resulted in enlarging the surface area occupied by the neurons which we speculate will augment processing of sensory information.

  2. Adaptation of Diaphyseal Structure With Aging and Increased Mechanical Usage in the Adult Rat: A Histomorphometrical and Biomechanical Study

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Li, Xiao Jian; Schaffler, Mitchell B.

    1991-01-01

    The experimental increase in mechanical usage or overloading of the left hindlimb was produced by immobilization of the contralateral hindlimb. The right hindlimb was placed in a flexed position against the body and was immobilized using an elastic bandage. Some control animals were sacrificed initially at time zero and increased mechanical usage and age-matched control animals were sacrificed after 2, 10, 18, and 26 weeks of treatment. All animals received double bone fluorochrome labeling prior to sacrifice. Cortical bone histomorphometry and cross-sectional moments of inertia were determined. Marrow cavity enlargement and total cross-sectional area expansion represented the age-related cortical bone changes. Increased mechanical usage enhanced periosteal bone modeling in the formation mode and dampened endocortical bone remodeling and bone modeling in the resorption mode (resorption drift) to create a slight positive bone balance. These observations are in general agreement with Frost's postulate for mechanical effects on bone modeling and remodeling. The maximum moment of inertia did not change significantly in either control or overloaded tibial shafts. The minimum and polar moment of inertias in overloaded bones increases over those of controls at 18 and 26 weeks of the experiment.

  3. Adaptation of Diaphyseal Structure with Aging and Increased Mechanical Usage in the Adult Rat: A Histomorphometrical and Biomechanical Study

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Li, Xiao Jian; Schaffler, Mitchell B.

    1991-01-01

    The experimental increase in mechanical usage or overloading of the left hindlimb was produced by immobilization of the contralateral hindlimb. The right hindlimb was placed in a flexed position against the body and was immobilized using an elastic bandage. Some control animals were sacrificed initially at time zero and increased mechanical usage and age-matched control animals were sacrificed after 2, 10, 18, and 26 weeks of treatment. All animals received double bone fluorochrome labeling prior to sacrifice. Cortical bone histomorphometry and cross-sectional moments of inertia were determined. Marrow cavity enlargement and total cross-sectional area expansion represented the age-related cortical bone changes. Increased mechanical usage enhanced periosteal bone modeling in the formation mode and dampened endocortical bone remodeling and bone modeling in the resorption mode (resorption drift) to create a slight positive bone balance. These observations are in general agreement with Frost's postulate for mechanical effects on bone modeling and remodeling. The maximum moment of inertia did not change significantly in either control or overloaded tibial shafts. The minimum and polar moment of inertias in overloaded bones increases over those of controls at 18 and 26 weeks of the experiment.

  4. Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro.

    PubMed Central

    Kaye, D; Pimental, D; Prasad, S; Mäki, T; Berger, H J; McNeil, P L; Smith, T W; Kelly, R A

    1996-01-01

    One of the trophic factors that has been implicated in initiating or facilitating growth in response to increased mechanical stress in several tissues and cell types is basic fibroblast growth factor (bFGF; FGF-2). Although mammalian cardiac muscle cells express bFGF, it is not known whether it plays a role in mediating cardiac adaptation to increased load, nor how release of the cytosolic 18-kD isoform of bFGF would be regulated in response to increased mechanical stress. To test the hypothesis that increased mechanical activity induces transient alterations in sarcolemmal permeability that allow cytosolic bFGF to be released and subsequently to act as an autocrine and paracrine growth stimulus, we examined primary isolates of adult rat ventricular myocytes maintained in serum-free, defined medium that were continually paced at 3 Hz for up to 5 d. Paced myocytes, but not nonpaced control cells, exhibited a "hypertrophic" response, which was characterized by increases in the rate of phenylalanine incorporation, total cellular protein content, and cell size. These changes could be mimicked in control cells by exogenous recombinant bFGF and could be blocked in continually paced cells by a specific neutralizing anti-bFGF antibody. In addition, medium conditioned by continually paced myocytes contained significantly more bFGF measured by ELISA and more mitogenic activity for 3T3 cells, activity that could be reduced by a neutralizing anti-bFGF antibody. The hypothesis that transient membrane disruptions sufficient to allow release of cytosolic bFGF occur in paced myocytes was examined by monitoring the rate of uptake into myocytes from the medium of 10-kD dextran linked to fluorescein. Paced myocytes exhibited a significantly higher rate of fluoresceinlabeled dextran uptake. These data are consistent with the hypothesis that nonlethal, transient alterations in sarcolemmal membrane permeability with release of cytosolic bFGF is one mechanism by which increased

  5. Intrauterine growth restriction increases the preference for palatable foods and affects sensitivity to food rewards in male and female adult rats.

    PubMed

    Dalle Molle, Roberta; Laureano, Daniela Pereira; Alves, Márcio Bonesso; Reis, Tatiane Madeira; Desai, Mina; Ross, Michael G; Silveira, Patrícia Pelufo

    2015-08-27

    Clinical evidence suggests that intrauterine growth restriction (IUGR) can cause persistent changes in the preference for palatable foods. In this study, we compared food preferences, the response to food rewards, and the role of the mesolimbic dopaminergic system in feeding behavior, between IUGR and control rats. Time-mated pregnant Sprague-Dawley rats were randomly allocated to a control group (standard chow ad libitum) or a 50% food restriction (FR) group, which received 50% of the control dams׳ habitual intake. These diets were provided from gestation day 10 to the 21st day of lactation. Within 24h of birth, pups were cross-fostered and divided into four groups: Adlib/Adlib, FR/Adlib, FR/FR, Adlib/FR. Standard chow consumption was compared between all groups. Food preferences, conditioned place preference to a palatable diet, and the levels of tyrosine hydroxylase (TH) phosphorylation and D2 receptors in the nucleus accumbens were analyzed and compared between the two groups of interest: Adlib/Adlib (control) and FR/Adlib (exposed to growth restriction during the fetal period only). IUGR adult rats had a stronger preference for palatable foods, but showed less conditioned place preference to a palatable diet than controls. D2 receptors levels were lower in IUGR rats. At baseline, TH and pTH levels were higher in FR/Adlib than control males. Measurements taken after exposure to sweet foods revealed higher levels of TH and pTH in FR/Adlib than control females. These data showed that IUGR rats exhibited a preference for palatable foods, potentially due to alterations in their mesolimbic reward pathway. Additionally, the changes observed in the mesolimbic dopaminergic system of IUGR rats proved to be sex-specific. This article is part of a Special Issue entitled 1618.

  6. 17β-Estradiol, but not estrone, increases the survival and activation of new neurons in the hippocampus in response to spatial memory in adult female rats.

    PubMed

    McClure, Robyn E S; Barha, Cindy K; Galea, Liisa A M

    2013-01-01

    Estrogens fluctuate across the lifespan in women, with circulating 17β-estradiol levels higher pre-menopause than estrone and circulating estrone levels higher postmenopause than 17β-estradiol. Estrone is a common component of hormone replacement therapies, but research shows that 17β-estradiol may have a greater positive impact on cognition. Previous studies show that acute estrone and 17β-estradiol impact hippocampus-dependent learning and cell proliferation in the dentate gyrus in a dose-dependent manner in adult female rats. The current study explores how chronic treatment with estrone and 17β-estradiol differentially influences spatial learning, hippocampal neurogenesis and activation of new neurons in response to spatial memory. Adult female rats received daily injections of vehicle (sesame oil), or a 10 μg dose of either 17β-estradiol or estrone for 20 days. One day following the first hormone injection all rats were injected with the DNA synthesis marker, bromodeoxyuridine. On days 11-15 after BrdU injection rats were trained on a spatial reference version of the Morris water maze, and five days later (day 20 of estrogens treatment) were given a probe trial to assess memory retention. Cell proliferation was assessed by the endogenous cell cycle marker, Ki67, cell survival was assessed by counting the number and density of BrdU-ir cells in the dentate gyrus and cell activation was assessed by the percentage of BrdU-ir cells that were co-labelled with the immediate early gene product zif268. There were no significant differences between groups in acquisition or retention of Morris water maze. However, the 17β-estradiol group had significantly higher, while the estrone group had significantly lower, levels of cell survival (BrdU-ir cells) in the dentate gyrus compared to controls. Furthermore, rats injected with 17β-estradiol showed significantly higher levels of activation of new neurons in response to spatial memory compared to controls. These

  7. Increased extracellular release of hippocampal NE is associated with tetanization of the medial perforant pathway in the freely moving adult male rat.

    PubMed

    Bronzino, J D; Kehoe, P; Mallinson, K; Fortin, D A

    2001-01-01

    The induction of long-term potentiation (LTP) within the dentate gyrus of the hippocampal formation is modulated by many afferent influences from a number of subcortical structures known to be intimately involved in hippocampal-dependent learning and memory. It has been demonstrated in slice and anesthetized preparations that norepinephrine (NE) is one of these major neuromodulators involved in the induction of LTP. However, the majority of these studies have not been conducted in the freely moving animal. Recently, we developed surgical procedures and instrumentation techniques to simultaneously record electrophysiological and neurochemical data from the hippocampal formation. The present study uses these techniques to examine the underlying neurochemical changes in the hippocampus associated with the induction of hippocampal dentate LTP in the freely moving adult rat. These findings establish baseline levels of NE that can be used to evaluate the impact of various tetanization paradigms as well as the effect of a variety of insults on hippocampal plasticity.

  8. Expiratory activation of abdominal muscle is associated with improved respiratory stability and an increase in minute ventilation in REM epochs of adult rats

    PubMed Central

    Andrews, Colin G.

    2015-01-01

    Breathing is more vulnerable to apneas and irregular breathing patterns during rapid eye movement (REM) sleep in both humans and rodents. We previously reported that robust and recurrent recruitment of expiratory abdominal (ABD) muscle activity is present in rats during REM epochs despite ongoing REM-induced muscle atonia in skeletal musculature. To develop a further understanding of the characteristics of ABD recruitment during REM epochs and their relationship with breathing patterns and irregularities, we sought to compare REM epochs that displayed ABD muscle recruitment with those that did not, within the same rats. Specifically, we investigated respiratory characteristics that preceded and followed recruitment. We hypothesized that ABD muscle recruitment would be likely to occur following respiratory irregularities and would subsequently contribute to respiratory stability and the maintenance of good ventilation following recruitment. Our data demonstrate that epochs of REM sleep containing ABD recruitments (REMABD+) were characterized by increased respiratory rate variability and increased presence of spontaneous brief central apneas. Within these epochs, respiratory events that displayed ABD muscle activation were preceded by periods of increased respiratory rate variability. Onset of ABD muscle activity increased tidal volume, amplitude of diaphragmatic contractions, and minute ventilation compared with the periods preceding ABD muscle activation. These results show that expiratory muscle activity is more likely recruited when respiration is irregular and its recruitment is subsequently associated with an increase in minute ventilation and a more regular respiratory rhythm. PMID:26338455

  9. 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

  10. Calcium overload increases oxidative stress in old rat gastrocnemius muscle.

    PubMed

    Capel, F; Demaison, L; Maskouri, F; Diot, A; Buffiere, C; Patureau Mirand, P; Mosoni, L

    2005-09-01

    In order to challenge in vivo muscle Ca2+ homeostasis and analyze consequences on mitochondrial H2O2 release (MHR) and sarcopenia, we injected Ca2+ ionophore A23187 (200 microg/kg, ip) in adult and old rats and measured gastrocnemius mass and mitochondrial Ca2+ content (MCC) using radioactive Ca2+ 48 h after injection. In a second experiment performed in old rats, we measured isocitrate dehydrogenase (ICDH) activity as an index of MCC, MHR, mitochondrial respiration, citrate synthase, COX and antioxydant enzyme activities 24 h after a 150 microg/kg injection. In adult rats, muscle mass and MCC were unchanged by A23187. In old rats, MCC increased 24 h after injection as reflected by a significant increase in ICDH activity; measured MCC tended to increase at 48 h. MHR and Mn-SOD activity were significantly increased at 24 h, and GPX activity was reduced. Muscle mass was unchanged but was negatively correlated with MCC in control and treated old rats. In conclusion, in old rats, A23187 probably induced a mitochondrial Ca2+ overload responsible for the observed increase in MHR without leading to muscle atrophy on a short term basis.

  11. Nicotine Increases Alcohol Intake in Adolescent Male Rats

    PubMed Central

    Lárraga, Armando; Belluzzi, James D.; Leslie, Frances M.

    2017-01-01

    Background: Use of alcohol and tobacco, the two most concurrently abused drugs, typically first occurs during adolescence. Yet, there have been no systematic analyses of ethanol (EtOH) and nicotine (Nic) interactions during adolescence. Recent animal studies report that kappa-opioid (KOR) receptor activation mediates age differences in drug reinforcement. Our hypothesis is that concurrent self-administration of EtOH and Nic will be greater in adolescent rats because of age differences in KOR function. Furthermore, exposure to alcohol and nicotine during adolescence has been reported to increase EtOH intake in adulthood. We performed a longitudinal animal study and hypothesized adolescent rats allowed to self-administer nicotine would drink more alcohol as adults. Methods: Adolescent, postnatal day (P)32, and adult (P90) male and female Sprague-Dawley rats were allowed to self-administer EtOH, Nic, or a combination of both, EtOH+Nic, in an intravenous self-administration paradigm. The role of KOR was pharmacologically evaluated with the KOR antagonist, norbinaltorphamine (norBNI) and with the KOR agonist, U50,488H. Alcohol drinking was subsequently evaluated with male rats in a drinking in the dark (DID), 2-bottle choice test. Results: Concurrent Nic increased EtOH intake in adolescent males, but not in adults or females. Pharmacological blockade of KOR with norBNI robustly increased EtOH+Nic self-administration in adult male rats, but had no effect with female rats. Lastly, in our longitudinal study with male rats, we found prior self-administration of Nic or EtOH+Nic during adolescence increased subsequent oral EtOH intake, whereas prior self-administration of EtOH alone in adults increased subsequent EtOH drinking. Conclusions: There are major age- and sex-differences in the reinforcing effects of EtOH+Nic. Adolescent males are sensitive to the reinforcing interactions of the two drugs, whereas this effect is inhibited by KOR activation in male adults. Nicotine

  12. Prenatal exposure to a low-frequency electromagnetic field demasculinizes adult scent marking behavior and increases accessory sex organ weights in rats

    SciTech Connect

    McGivern, R.F.; Sokol, R.Z.; Adey, W.R.

    1990-01-01

    Pregnant Sprague-Dawley dams were exposed to a low-level, low-frequency pulsed electromagnetic (EM) field (15 Hz, 0.3 msec duration, peak intensity 8 gauss) for 15 min twice a day from day 15 through day 20 of gestation, a period in development that is critical for sexual differentiation of the male rat brain. No differences in litter size, number of stillborns, or body weight were observed in offspring from field-exposed dams. At 120 days of age, field-exposed male offspring exhibited significantly less scent marking behavior than controls. Accessory sex organ weights, including epididymis, seminal vesicles, and prostate, were significantly higher in field-exposed subjects at this age. However, circulating levels of testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as epididymal sperm counts, were normal. These data indicate that brief, intermittent exposure to low-frequency EM fields during the critical prenatal period for neurobehavioral sex differentiation can demasculinize male scent marking behavior and increase accessory sex organ weights in adulthood.

  13. L-DOPA-induced dyskinesia in adult rats with a unilateral 6-OHDA lesion of dopamine neurons is paralleled by increased c-fos gene expression in the subthalamic nucleus.

    PubMed

    Soghomonian, Jean-Jacques

    2006-05-01

    Levodopa (L-DOPA), the metabolic precursor of dopamine, is widely used as a pharmacological agent for the symptomatic treatment of Parkinson's disease. However, long-term L-DOPA use results in abnormal involuntary movements such as dyskinesias. There is evidence that abnormal cell signaling in the basal ganglia is involved in L-DOPA-induced dyskinesia. The subthalamic nucleus (STN) plays a key role in the circuitry of the basal ganglia and in the pathophysiology of Parkinson's disease. However, the contribution of the STN to L-DOPA-induced dyskinesias remains unclear. The objective of this work was to study the effects of acute or chronic systemic administration of L-DOPA to adult rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of dopamine neurons on c-fos expression in the STN and test the hypothesis that these effects correlate with L-DOPA-induced dyskinesias. c-fos mRNA expression was measured in the STN by in situ hybridization histochemistry at the single cell level. Our results confirm earlier evidence that the chronic administration of L-DOPA to rats with a unilateral 6-OHDA lesion increases c-fos expression in the STN. We also report that c-fos expression can be increased following an acute injection of L-DOPA to 6-OHDA-lesioned rats but not following a chronic injection of L-DOPA to sham-operated, unlesioned rats. Finally, we provide evidence that the occurrence and severity of dyskinesia is correlated with c-fos mRNA levels in the ipsilateral STN. These results suggest that altered cell signaling in the STN is involved in some of the behavioral effects induced by systemic L-DOPA administration.

  14. Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons

    PubMed Central

    Gajewska-Woźniak, Olga; Grycz, Kamil; Czarkowska-Bauch, Julita; Skup, Małgorzata

    2016-01-01

    The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c—interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG). LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF) using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models of injury is a

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. 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.

  1. 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

  2. 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.

  3. Increasing Employment Opportunities for Disadvantaged Young Adults

    ERIC Educational Resources Information Center

    Hossain, Farhana; Terwelp, Emily

    2015-01-01

    In the past four decades, profound changes in the U.S. economy--including falling wages, widening inequality, and the polarization of jobs at the top and bottom of the education and wage distributions--have had dramatic implications for the labor-market fortunes of young adults. Only about half of young people ages 16 to 24 held jobs in 2014, and…

  4. 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.

  5. 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.

  6. Adults as Learners. Increasing Participation and Facilitating Learning.

    ERIC Educational Resources Information Center

    Cross, K. Patricia

    The literature on adult learners is reviewed, and two models of adult learning are developed. Demographic, social, and technological trends that stimulate the increasing demand for learning opportunities are examined, and the views of those who see dangers in new pressures on adults to participate in organized learning activities are considered.…

  7. 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

  8. 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.

  9. Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

    PubMed

    Cruz, G; Riquelme, R; Espinosa, P; Jara, P; Dagnino-Subiabre, A; Renard, G M; Sotomayor-Zárate, R

    2014-05-01

    Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter.

  10. 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.

  11. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.

    PubMed

    Sahay, Amar; Scobie, Kimberly N; Hill, Alexis S; O'Carroll, Colin M; Kheirbek, Mazen A; Burghardt, Nesha S; Fenton, André A; Dranovsky, Alex; Hen, René

    2011-04-28

    Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal

  12. Differential Outcomes of Adult Education on Adult Learners' Increase in Social Inclusion

    ERIC Educational Resources Information Center

    de Greef, Maurice; Verté, Dominique; Segers, Mien

    2015-01-01

    To date a significant share of the European population can be considered at risk of social exclusion. It has been argued that adult education programmes are a powerful tool to support vulnerable adults increasing their social inclusion. This study aims to answer the question if and which subgroups of vulnerable adults experience an increase in…

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Estradiol increases growth hormone secretion in rats exposed to swimming stress or reserpine treatment.

    PubMed

    Eriksson, E; Jansson, J O

    1985-09-30

    The secretory pattern of growth hormone (GH) in female rats differs from that in males with respect to e.g. the inter-peak baseline levels being higher in females. In the present study the influence of sex steroids on plasma GH levels was investigated in male rats under various conditions. Administration of estradiol, but not testosterone, was found to increase GH release in rats with suppressed levels induced by exposure to swimming stress or by treatment with the monoamine depleting agent reserpine. In line with previous studies, administration of estradiol was found to increase also inter-peak GH levels in adult male rats; i.e. to cause a feminization of the secretory pattern. In stressed and in reserpinized animals as well as in normal male rats, the effect of estradiol is similar to that earlier demonstrated for somatostatin antiserum, and hence it is suggested that estradiol may act antagonistic to the GH inhibiting factor.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Dividing attention lowers children's but increases adults' false memories.

    PubMed

    Otgaar, Henry; Peters, Maarten; Howe, Mark L

    2012-01-01

    The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a divided attention task. The results showed that divided attention affected children's and adults' false memory levels differently but did not alter true memory differently. Our results revealed a developmental shift in that divided attention lowered children's false memory rates but increased adults' false memory rates, regardless of the nature of the material (i.e., neutral or negative). Our study indicates that manipulations that target conscious processing (e.g., divided attention) result in marked qualitative and quantitative differences between children's and adults' false memories but not true memories.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Repeated administration of adenosine increases its cardiovascular effects in rats.

    PubMed

    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Increased gluconeogenesis in rats exposed to hyper-G stress

    NASA Technical Reports Server (NTRS)

    Daligcon, B. C.; Oyama, J.; Hannak, K.

    1985-01-01

    The effect of glucogenesis on the plasma glucose and liver glycogen of rats exposed to hyper-G stress is investigated. Twelve male Sprague-Dawley rats are injected with C-14 lactate, alanine, of glycerol, and six of the rats are exposed to 3.1 G for 0.25, 0.50, and 1.0 hr. The plasma glucose and liver glycogen of the centrifuged and noncentrifuged rats are analyzed. A significant increase in the C-14 incorporation of the substrate into the plasma glucose and liver glycogen is observed in the centrifuged rats. The injection of 5-methoxyindole-2-carboxylic acid, a gluconeogenesis inhibitor, results in a blocked increase in plasma glucose and liver glycogen. The role of epinephrine on the hyperglycemic and liver glycogen responses of centrifuged rats is studied. It is concluded that the initial increase in plasma glucose and liver glycogen in rats exposed to hyper-G stress is the result of an increased rate of gluconeogenesis.

  18. 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.

  19. 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.

  20. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    SciTech Connect

    Feng, Shan-Li; Sun, Ming-Rui; Li, Ting-Ting; Yin, Xin; Xu, Chang-Qing; Sun, Yi-Hua

    2011-03-11

    Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3

  1. 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.

  2. Hunting increases adaptive auditory map plasticity in adult barn owls.

    PubMed

    Bergan, Joseph F; Ro, Peter; Ro, Daniel; Knudsen, Eric I

    2005-10-19

    The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.

  3. Increasing the Success of Adults from Diverse Populations.

    ERIC Educational Resources Information Center

    Sheckley, Barry G.; Keeton, Morris T.

    1995-01-01

    The following methods can increase the academic success of adults from diverse populations: focus on how educational circumstances are experienced by individuals, not broad groups; maximize time spent on tasks related to course/degree requirements; and reduce student costs in terms of time, money, frustration, and stress. (SK)

  4. Thematic Solutions Using Young Adult Literature to Increase Reading Comprehension

    ERIC Educational Resources Information Center

    Adams, Jill; Bushman, John H.

    2006-01-01

    In this article, the authors discuss thematic solutions using young adult literature to increase reading comprehension. Here, they emphasize that prior knowledge plays a very important role in the reading process. As students read, they actively "construct meaning through the integration of existing and new knowledge and the flexible use of…

  5. Increasing Student/Older Adult Interaction by Life Review Assignments.

    ERIC Educational Resources Information Center

    Sumner, Edward D.; Haight, Barbara K.

    1993-01-01

    A method for increasing interaction between students and older adults in a geriatric pharmacy course uses an instructional module on stereotypes, age and personality, role changes, and nursing home living. The course requires students to conduct a life review of someone over age 65. The exercise improves student communication skills and…

  6. Periadolescent rats (P41-50) exhibit increased susceptibility to D-methamphetamine-induced long-term spatial and sequential learning deficits compared to juvenile (P21-30 or P31-40) or adult rats (P51-60).

    PubMed

    Vorhees, Charles V; Reed, Tracy M; Morford, LaRonda L; Fukumura, Masao; Wood, Sandra L; Brown, Carrie A; Skelton, Matthew R; McCrea, Anne E; Rock, Stephanie L; Williams, Michael T

    2005-01-01

    We have previously shown that P11-20 treatment with d-methamphetamine (MA) induces impaired spatial navigation in the Morris water maze (MWM), whereas P1-10 treatment does not. Little is known about the long-term behavioral consequences of MA during juvenile, adolescent, and early adult brain development. In dose-response experiments, we tested successive 10-day intervals of exposure to MA in rats (P21-30, P31-40, P41-50, and P51-60; four doses per day). MA dosing prior to P21 produces little or no toxicity; however, we observed an increased toxicity with advancing age. Across-age comparisons revealed no MWM acquisition or Cincinnati water maze (CWM) effects after MA treatment on P21-30 (2.5-10 mg/kg/dose), P31-40 (1.25-7.5 mg/kg/dose), or P51-60 (1.25-5.0 mg/kg/dose); however, significantly impaired MWM acquisition was observed after P41-50 MA treatment at the highest dose (6.25 mg/kg/dose). Learning in the CWM was also impaired in this group. No effects were seen at 1.25, 2.5, or 5 mg/kg/dose following P41-50 MA treatment. MWM reversal learning trials after P41-50 treatment showed a trend towards longer latency in all MA dose groups, but no effect on double-reversal trials. Reversal and double-reversal also showed no effects at the other exposure ages. No differences in straight channel swimming or cued learning in the MWM were seen after MA treatment at any exposure age. P41-50 is the periadolescent stage of brain development in rodents. The effects observed at this age may suggest a previously unrecognized period of susceptibility for MA-induced cognitive deficits.

  7. Identification of a pheromone that increases anxiety in rats

    PubMed Central

    Inagaki, Hideaki; Kiyokawa, Yasushi; Tamogami, Shigeyuki; Watanabe, Hidenori; Takeuchi, Yukari; Mori, Yuji

    2014-01-01

    Chemical communication plays an important role in the social lives of various mammalian species. Some of these chemicals are called pheromones. Rats release a specific odor into the air when stressed. This stress-related odor increases the anxiety levels of other rats; therefore, it is possible that the anxiety-causing molecules are present in the stress-related odorants. Here, we have tried to identify the responsible molecules by using the acoustic startle reflex as a bioassay system to detect anxiogenic activity. After successive fractionation of the stress-related odor, we detected 4-methylpentanal and hexanal in the final fraction that still possessed anxiogenic properties. Using synthetic molecules, we found that minute amounts of the binary mixture, but not either molecule separately, increased anxiety in rats. Furthermore, we determined that the mixture increased a specific type of anxiety and evoked anxiety-related behavioral responses in an experimental model that was different from the acoustic startle reflex. Analyses of neural mechanisms proposed that the neural circuit related to anxiety was only activated when the two molecules were simultaneously perceived by two olfactory systems. We concluded that the mixture is a pheromone that increases anxiety in rats. To our knowledge, this is the first study identifying a rat pheromone. Our results could aid further research on rat pheromones, which would enhance our understanding of chemical communication in mammals. PMID:25512532

  8. Identification of a pheromone that increases anxiety in rats.

    PubMed

    Inagaki, Hideaki; Kiyokawa, Yasushi; Tamogami, Shigeyuki; Watanabe, Hidenori; Takeuchi, Yukari; Mori, Yuji

    2014-12-30

    Chemical communication plays an important role in the social lives of various mammalian species. Some of these chemicals are called pheromones. Rats release a specific odor into the air when stressed. This stress-related odor increases the anxiety levels of other rats; therefore, it is possible that the anxiety-causing molecules are present in the stress-related odorants. Here, we have tried to identify the responsible molecules by using the acoustic startle reflex as a bioassay system to detect anxiogenic activity. After successive fractionation of the stress-related odor, we detected 4-methylpentanal and hexanal in the final fraction that still possessed anxiogenic properties. Using synthetic molecules, we found that minute amounts of the binary mixture, but not either molecule separately, increased anxiety in rats. Furthermore, we determined that the mixture increased a specific type of anxiety and evoked anxiety-related behavioral responses in an experimental model that was different from the acoustic startle reflex. Analyses of neural mechanisms proposed that the neural circuit related to anxiety was only activated when the two molecules were simultaneously perceived by two olfactory systems. We concluded that the mixture is a pheromone that increases anxiety in rats. To our knowledge, this is the first study identifying a rat pheromone. Our results could aid further research on rat pheromones, which would enhance our understanding of chemical communication in mammals.

  9. Increased rewarding properties of morphine in perinatally protein-malnourished rats.

    PubMed

    Valdomero, A; Velazquez, E E; de Olmos, S; de Olmos, J S; Orsingher, O A; Cuadra, G R

    2007-12-05

    In the current research, we assessed the influence of a protein malnutrition schedule from the 14th day of gestation up to 40 days of age (D-rats) on the rewarding properties of morphine in adult rats by means of the conditioned place preference paradigm. Well-nourished animals (C-rats) administered with different doses of morphine (0.75, 1.5, 3, 6, 12 or 24 mg/kg i.p.) exhibited a conditioning place preference with doses of 3 and 6 mg/kg, whereas in D-rats such a conditioning effect was observed with doses of 1.5 and 3 mg/kg. No adverse effects were observed in either C- or D-rats for the higher doses of morphine. In addition, when animals of both groups were pretreated twice a day for 3 days with increasing doses of morphine (5, 10 and 20 mg/kg s.c.), only D-rats elicited sensitization to the conditioning effect with the lowest dose of morphine (0.75 mg/kg i.p.). Furthermore, sensitized D-rats showed a selective and significant increase in FosB expression in the nucleus accumbens (core and shell), basolateral amygdala and medial prefrontal cortex, brain areas that are functionally related to the rewarding neural circuit. These results demonstrate that a deficient nutritional status during the perinatal period results in adult subjects having neural alterations, leading to an increased responsiveness to morphine and/or enhanced reinforcement effects, which correlates with an overexpression of FosB in selective brain areas related to the rewarding network.

  10. Smoking in Movies and Increased Smoking Among Young Adults

    PubMed Central

    Song, Anna V.; Ling, Pamela M.; Neilands, Torsten B.; Glantz, Stanton A.

    2010-01-01

    Objective This study assessed whether smoking in the movies was associated with smoking in young adults. Methods A national web-enabled cross-sectional survey of 1528 young adults, aged 18–25, was performed between September and November 2005. Logistic regression and path analysis using probit regression were used to assess relationships between exposure to smoking in the movies and smoking behavior. Analysis was completed in December 2006. Results Exposure to smoking in the movies predicted current smoking. The adjusted odds of current smoking increased by a factor of 1.21 for each quartile increase in exposure to smoking (p<0.01) in the movies, reaching 1.77 for the top exposure quartile. The unadjusted odds of established smoking (100+ cigarettes with current smoking) increased by 1.23 per quartile (p<0.001) of exposure, reaching 1.86 for the top quartile. This effect on established smoking was mediated by two factors related to smoking in the movies: positive expectations about smoking and exposure to friends and relatives who smoked, with positive expectations accounting for about two thirds of the effect. Conclusions The association between smoking in the movies and young adult smoking behavior exhibited a dose–response relationship; the more a young adult was exposed to smoking in the movies, the more likely he or she would have smoked in the past 30 days or have become an established smoker. PMID:17950405

  11. 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.

  12. 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

  13. 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.

  14. Increased GABAB receptor signaling in a rat model for schizophrenia

    PubMed Central

    Selten, Martijn M.; Meyer, Francisca; Ba, Wei; Vallès, Astrid; Maas, Dorien A.; Negwer, Moritz; Eijsink, Vivian D.; van Vugt, Ruben W. M.; van Hulten, Josephus A.; van Bakel, Nick H. M.; Roosen, Joey; van der Linden, Robert J.; Schubert, Dirk; Verheij, Michel M. M.; Kasri, Nael Nadif; Martens, Gerard J. M.

    2016-01-01

    Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20–22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia. PMID:27687783

  15. Increased GABAB receptor signaling in a rat model for schizophrenia.

    PubMed

    Selten, Martijn M; Meyer, Francisca; Ba, Wei; Vallès, Astrid; Maas, Dorien A; Negwer, Moritz; Eijsink, Vivian D; van Vugt, Ruben W M; van Hulten, Josephus A; van Bakel, Nick H M; Roosen, Joey; van der Linden, Robert J; Schubert, Dirk; Verheij, Michel M M; Kasri, Nael Nadif; Martens, Gerard J M

    2016-09-30

    Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.

  16. 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.

  17. 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

  18. Altered conformation and increased strand breaks in neuronal and astroglial DNA of aging rat brain.

    PubMed

    Bhaskar, M S; Rao, K S

    1994-05-01

    Melting temperatures (Tm) of the DNA isolated from young, adult, and old rat brain neurons and astrocytes were recorded under different conditions. There was a rise in Tm and decrease in hyperchromicity in the old when compared to the young and adult. Single and double strand breaks were assessed by using nick translation type incubation of DNA with E. coli Pol I and addition of nucleotides at the terminal 3'-OH by calf thymus terminal deoxynucleotidyl transferase. Results show that DNA from old brain cells is more compact in conformation. However, there is also an increase in the number of single and double strand breaks with age in both neuronal and astroglial DNA.

  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. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Microwave-induced increase of water and conductivity in submaxillary salivary gland of rats

    SciTech Connect

    Mikolajczyk, H.

    1981-01-01

    Hypersalivation is an important mechanism for heat dissipation by animals without sweat glands. The water content and conductivity (at 20 kHz) in submaxillary salivary glands (SSG) and in other tissues were investigated in adult male rats exposed to microwaves (2880 MHz, 1.5 microsecond pulses at 1000 Hz) or to conventional heat at 40 degrees C. Eighty rats in one series were exposed, one at a time, for 30 min to microwaves producing a specific absorption rate (SAR) of 4.2, 6.3, 6.8, 8.4, 10.8 or 12.6 W/kg. Fifty rats were sham-exposed under similar environmental conditions. In the second series, ten rats were sham-exposed, 33 rats were exposed one at time, for 15, 30 or 60 min to microwaves at a SAR of 9.5 W/kg, and 32 rats were exposed for similar periods to conventional heat at 40 degrees C. In rats of the first series colonic temperatures were elevated significantly at a SAR of 4.2 W/kg, while SSG water content and conductivity increased significantly at SAR values of 6.3 W/kg and higher. In the second series of experiments increases in colonic temperature and SSG water content were greater after 15 and 30 min of microwave exposure than after exposure to heat. Also, SSG conductivity was significantly depressed by heat and significantly increased by microwaves after exposure for 15 or 30 min. The results support the hypothesis that water content and conductivity of SSG of rats can be used as a sensitive specific test of a microwave induced thermal response.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Predator odor exposure increases food-carrying behavior in rats.

    PubMed

    Wernecke, Kerstin E A; Brüggemann, Judith; Fendt, Markus

    2016-02-01

    To cover their energy demands, prey animals are forced to search for food. However, during foraging they also expose themselves to the risk of becoming the prey of predators. Consequently, in order to increase their fitness foraging animals have to trade-off efficiency of foraging against the avoidance of predation risk. For example, the decision on whether a found food piece should be eaten at the food source or whether it should be carried to a protective site such as the nest (food-carrying behavior), is strongly dependent on different incentive factors (e.g., hunger level, food size, distance to the nest). It has been shown that food-carrying behavior increases the more risky the foraging situation becomes. Since predator odors are clearly fear-inducing in rats, we ask here whether the detection of predator odors in close proximity to the food source modulates food-carrying behavior. In the present study, the food-carrying behavior of rats for six different food pellet sizes was measured in a "low risk" and a "high risk" testing condition by presenting water or a fox urine sample, respectively, next to the food source. For both testing conditions, food-carrying behavior of rats increased with increasing food pellet weight. Importantly, the proportion of food-carrying rats was significantly higher during exposure to fox urine ("high risk") than when rats were tested with the water control ("low risk"). Taken together, these results demonstrate that food-carrying behavior of rats is increased by the detection of a predator odor. Our data also support the idea that such food-carrying behavior can be considered as a pre-encounter defensive response.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Increased Renal Solute Excretion in Rats Following Space Flight

    NASA Technical Reports Server (NTRS)

    Wade, Charles E.; Moore, A. L.; Morey-Holton, E.

    1995-01-01

    Following space flight a diuresis, due to an increase in free water clearance, has been suggested in humans. To assess the effects of space flight on renal function, rats were flown in space for 14 days. Rats were divided into three groups; vivarium controls (V;n=6; housed 2/shoe box cage), flight controls (FC;n=6; group housed in a flight cage), and flight animals (F;n=6). Upon landing all animals were placed into individual metabolic cages. Urine was collected daily for 7 days and every other day for 14 days. Urine output was increased (p less than 0.05; ANOVA) following flight for 3 days. On postflight day 1, flow rates were, V=6.8 plus or minus 0.9, FC=8.711.8 and F=16.6 plus or minus 2.7 microliter/min. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate (V=7.9 plus or minus 0.9, FC=6.1 plus or minus 0.7 and F=13.5 plus or minus 0.7 uOsm/min). Creatinine excretion rate was increased over the first two postflight days. In the absence of changes in plasma creatinine, Na+, or K+ (samples obtained immediately post flight from similar rats compared to Day 14), GFR was increased following space flight. The increased excretion of solute was thus the result of increased delivery and decreased reabsorption. Osmotic clearance was increased (V=28, FC=27 and F=51 microliter/min), while free water clearance was decreased post flight (V=-21,FC=-18 and F=-34 microliter/min). In rats, the postflight diuresis is the result of an increase in solute (osmotic) excretion with an accompanying reduction in free water clearance.

  1. 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.

  2. Increased putamen volume in adults with autism spectrum disorder.

    PubMed

    Sato, Wataru; Kubota, Yasutaka; Kochiyama, Takanori; Uono, Shota; Yoshimura, Sayaka; Sawada, Reiko; Sakihama, Morimitsu; Toichi, Motomi

    2014-01-01

    Basal ganglia (BG) abnormalities are implicated in the pathophysiology of autism spectrum disorder (ASD). However, studies measuring the volume of the entire BG in individuals with ASD have reported discrepant findings, and no study conducted volume measurement of the entire substructures of the BG (the caudate, putamen, nucleus accumbens, and globus pallidus) in individuals with ASD. We delineated the BG substructures and measured their volumes in 29 adults with ASD without intellectual disabilities and 29 age- and gender-matched typically developed adult controls. We acquired T1-weighted anatomical images and performed semiautomated delineation and volume measurements of the above-mentioned subregions. Total cerebral volumes, sex, and ages were partialed out. Compared with controls, the putamen was significantly larger in the ASD group. The increased volume of the putamen found in high-functioning adults with ASD suggests that structural or histological abnormalities of the putamen may underlie the pathologies of ASD, such as repetitive and stereotyped behaviors and impaired social interactions.

  3. Hyberbaric oxygen increases atresia in normal & steroid induced PCO rat ovaries

    PubMed Central

    2012-01-01

    Background In this study, we investigated the effect of hyperbaric oxygen therapy (HBOT) on the morphology of estradiol valerate (EV) induced polycystic ovary (PCO) to find a new treatment modality for improvement of PCO. Methods The rats were divided into four groups. Group1, control; group 2, PCO group; group 3, PCO with HBOT group and group 4, normal ovary with HBOT. PCO was induced by a single intramuscular injection of 4 mg EV in adult cycling rats. Other rats with normal ovaries had oil injection as placebo. HBOT was applied to third and fourth groups for six weeks. Histopathologic evaluation of ovaries of all groups were performed & compared. Results Six weeks of HBOT was resulted in increase in follicular atresia, decrease in the number of primary, secondary, tertiary follicles and decrease in the number of fresh corpus luteum in normal rat ovary. HBOT on polycystic rat ovary, resulted in significant increase in atretic follicles which were already present. Conclusions HBOT of six weeks itself, changed ovarian morphology in favor of atresia both in PCO group and control group. This result of aggravated follicular atresia after HBOT on EV induced PCO may be due to long-term exposure in our protocol which with this state seems to be inapplicable in the improvement of PCO morphology. PMID:22309835

  4. 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.

  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. 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.

  7. 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.

  8. Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats.

    PubMed

    Amodeo, Leslie R; Kneiber, Diana; Wills, Derek N; Ehlers, Cindy L

    2017-03-01

    Binge drinking and the onset of alcohol-use disorders usually peak during the transition between late adolescence and early adulthood, and early adolescent onset of alcohol consumption has been demonstrated to increase the risk for alcohol dependence in adulthood. In the present study, we describe an animal model of early adolescent alcohol consumption where animals drink unsweetened and unflavored ethanol in high concentrations (20%). Using this model, we investigated the influence of drinking on alcohol-related appetitive behavior and alcohol consumption levels in early adulthood. Further, we also sought to investigate whether differences in alcohol-related drinking behaviors were specific to exposure in adolescence versus exposure in adulthood. Male Wistar rats were given a 2-bottle choice between 20% ethanol and water in one group and between two water bottles in another group during their adolescence (Postnatal Day [PD] 26-59) to model voluntary drinking in adolescent humans. As young adults (PD85), rats were trained in a paradigm that provided free access to 20% alcohol for 25 min after completing up to a fixed-ratio (FR) 16 lever press response. A set of young adult male Wistar rats was exposed to the same paradigm using the same time course, beginning at PD92. The results indicate that adolescent exposure to alcohol increased consumption of alcohol in adulthood. Furthermore, when investigating differences between adolescent high and low drinkers in adulthood, high consumers continued to drink more alcohol, had fewer FR failures, and faster completion of FR schedules in adulthood, whereas the low consumers were no different from controls. Rats exposed to ethanol in young adulthood also increased future intake, but there were no differences in any other components of drinking behavior. Both adolescent- and adult-exposed rats did not exhibit an increase in lever pressing during the appetitive challenge session. These data indicate that adolescent and early

  9. 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

  10. 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

  11. Life expectancy without depression increases among Brazilian older adults

    PubMed Central

    Andrade, Flávia Cristina Drumond; Wu, Fan; Lebrão, Maria Lúcia; Duarte, Yeda Aparecida de Oliveira

    2016-01-01

    ABSTRACT OBJECTIVE To estimate life expectancy with and without depressive symptoms in older adults for the years 2000 and 2010. METHODS We evaluated individuals aged 60 years or older (n = 1,862 in 2000 and n = 1,280 in 2010), participants of the Saúde, Bem-Estar e Envelhecimento (SABE – Health, Wellbeing and Aging) study in in Sao Paulo, Southeastern Brazil. Depression was measured using the shorter version of the Geriatric Depression Scale (GDS-15); respondents scoring ≥ 6 were classified as having depression. Estimates of life expectancy with and without depression were obtained using the Sullivan method. RESULTS Data from 2000 indicate that 60-year-old men could expect to live, on average, 14.7 years without depression and 60-year-old women could expect to live 16.5 years without depression. By 2010, life expectancy without depression had increased to 16.7 years for men and 17.8 years for women. Expected length of life with depression differed by sex, with women expected to live more years with depression than men. CONCLUSIONS Between 2000 and 2010, life expectancy without depression in Sao Paulo increased. However, older adults in Brazil, especially older women, still face a serious burden of mental illness. PMID:27143612

  12. [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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  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. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. NOS inhibition increases bubble formation and reduces survival in sedentary but not exercised rats.

    PubMed

    Wisløff, Ulrik; Richardson, Russell S; Brubakk, Alf O

    2003-01-15

    Previously we have shown that chronic as well as a single bout of exercise 20 h prior to a simulated dive protects rats from severe decompression illness (DCI) and death. However, the mechanism behind this protection is still not known. The present study determines the effect of inhibiting nitric oxide synthase (NOS) on bubble formation in acutely exercised and sedentary rats exposed to hyperbaric pressure. A total of 45 adult female Sprague-Dawley rats (270-320 g) were randomly assigned into exercise or sedentary control groups, with and without NOS inhibition, using L-NAME (0.05 or 1 mg ml(-1)) (a nonselective NOS inhibitor). Exercising rats ran intervals on a treadmill for 1.5 h, 20 h prior to the simulated dive. Intervals alternated between 8 min at 85-90 % of maximal oxygen uptake, and 2 min at 50-60 %. Rats were compressed (simulated dive) in a pressure chamber, at a rate of 200 kPa min(-1) to a pressure of 700 kPa, and maintained for 45 min breathing air. At the end of the exposure period, rats were decompressed linearly to the "surface" (100 kPa) at a rate of 50 kPa min(-1). Immediately after reaching the surface the animals were anaesthetised and the right ventricle was insonated using ultrasound. The study demonstrated that sedentary rats weighing more than 300 g produced a large amount of bubbles, while those weighing less than 300 g produced few bubbles and most survived the protocol. Prior exercise reduced bubble formation and increased survival in rats weighing more than 300 g, confirming the results from the previous study. During NOS inhibition, the simulated dive induced significantly more bubbles in all sedentary rats weighing less than 300 g. However, this effect could be attenuated by a single bout of exercise 20 h before exposure. The present study demonstrates two previously unreported findings: that administration of L-NAME allows substantial bubble formation and decreased survival in sedentary rats, and that a single bout of exercise

  7. Increased nitrite reductase activity of fetal versus adult ovine hemoglobin

    PubMed Central

    Blood, Arlin B.; Tiso, Mauro; Verma, Shilpa T.; Lo, Jennifer; Joshi, Mahesh S.; Azarov, Ivan; Longo, Lawrence D.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Power, Gordon G.

    2009-01-01

    Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus. PMID:19028797

  8. 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

  9. Increased Salivary Nitrite and Nitrate Excretion in Rats with Cirrhosis.

    PubMed

    Mahmoodi, Somayeh; Rahmatollahi, Mahdieh; Shahsavari, Fatemeh; Shafaroodi, Hamed; Grayesh-Nejad, Siyavash; Dehpour, Ahmad R

    2015-11-01

    Increased nitric oxide (NO) formation is mechanistically linked to pathophysiology of the extrahepatic complications of cirrhosis. NO is formed by either enzymatic or non-enzymatic pathways. Enzymatic production is catalyzed by NO synthase (NOS) while entero-salivary circulation of nitrate and nitrite is linked to non-enzymatic formation of NO under acidic pH in the stomach. There is no data on salivary excretion of nitrate and nitrite in cirrhosis. This study was aimed to investigate salivary levels of nitrate and nitrite in a rat model of biliary cirrhosis. Cirrhosis was induced by bile duct ligation (BDL). Four weeks after the operation, submandibular ducts of anesthetized BDL and control rats were cannulated with polyethylene microtube for saliva collection. Assessment of pH, nitrite and nitrate levels was performed in our research. We also investigated NOS expression by real time RT-PCR to estimate eNOS, nNOS and iNOS mRNA levels in the submandibular glands. Salivary pH was significantly lower in BDL rats in comparison to control animals. We also observed a statistically significant increase in salivary levels of nitrite as well as nitrate in BDL rats while there was no elevation in the mRNA expression of nNOS, eNOS, and iNOS in submandibular glands of cirrhotic groups. This indicates that an increased salivary level of nitrite/nitrate is less likely to be linked to increased enzymatic production of NO in the salivary epithelium. It appears that nitrate/nitrite can be transported from the blood stream by submandibular glands and excreted into saliva as entero-salivary circulation, and this mechanism may have been exaggerated during cirrhosis.

  10. A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

    PubMed

    Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

    2014-06-01

    Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

  11. 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.

  12. 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

  13. 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

  14. Increased gluconeogenesis in rats exposed to hyper-G stress

    NASA Technical Reports Server (NTRS)

    Daligcon, B. C.; Oyama, J.; Hannak, K.

    1985-01-01

    The effect of gluconeogenesis on the levels of plasma glucose and liver glycogen was studied in rats exposed to hyper-G stress. Incorporation of lactate, alanine, or glycerol, labeled with C-14, into plasma glucose and liver glycogen was measured in rats centrifuged at 3.1 G for 0.25, 0.50, and 1.0-hr periods, and was compared to noncentrifuged controls injected with appropriate glycogen precursors. It was found that exposure to G-stress leads to increased incorporation from all three substrates into both plasma glucose and liver glycogen. These early incorporation increases were blocked upon pre-G administration of 5-methoxyindole-2-carboxylic acid, a gluconeogenesis inhibitor, or propanolol, a beta-adrenergic blocker, as well as by adrenodemedullation. Results indicate that the rapid rise in plasma glucose, as well as in liver glycogen in rats exposed to hyper-G stress is due to an increased rate of gluconeogenesis, and that epinephrine, released in response to hyper-G-induced activation of the sympathetic-adrenal system, plays a dominant role during the early stages of hyper-G stress.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Tetrahydrohyperforin increases adult hippocampal neurogenesis in wild-type and APPswe/PS1ΔE9 mice.

    PubMed

    Abbott, Ana C; Calderon Toledo, Carla; Aranguiz, Florencia C; Inestrosa, Nibaldo C; Varela-Nallar, Lorena

    2013-01-01

    Tetrahydrohyperforin (IDN5706), a semi-synthetic derivative of hyperforin, has shown neuroprotective properties preventing the impairment of synaptic plasticity and cognitive decline in an in vivo model of Alzheimer's disease (AD). Considering the reported role of adult neurogenesis in the plasticity of the hippocampal network, we investigated whether IDN5706 affects adult neurogenesis and hippocampal function. In hippocampal progenitors cultured from adult rats, IDN5706 increased proliferation. Moreover, treatment with IDN5706 for 4 weeks increased cell proliferation in the subgranular zone (SGZ) of the hippocampus in 2 month-old wild-type mice in vivo. As determined by double labeling with BrdU and neuronal markers, IDN5706 treatment increased the number of immature neurons and newborn mature neurons in the adult dentate gyrus. In addition, IDN5706 treatment improved long-term memory in a hippocampal-dependent spatial memory task. Finally, IDN5706 treatment increased cell proliferation and neural commitment in the SGZ of the double transgenic APPswe/PS1ΔE9 mouse model of AD. These results indicate that IDN5706 increases adult hippocampal neurogenesis and may have therapeutic value in neurological disorders in which adult neurogenesis is impaired.

  2. 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.

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  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. Benzyl alcohol increases voluntary ethanol drinking in rats.

    PubMed

    Etelälahti, T J; Eriksson, C J P

    2014-09-01

    The anabolic steroid nandrolone decanoate has been reported to increase voluntary ethanol intake in Wistar rats. In recent experiments we received opposite results, with decreased voluntary ethanol intake in both high drinking AA and low drinking Wistar rats after nandrolone treatment. The difference between the two studies was that we used pure nandrolone decanoate in oil, whereas in the previous study the nandrolone product Deca-Durabolin containing benzyl alcohol (BA) was used. The aims of the present study were to clarify whether the BA treatment could promote ethanol drinking and to assess the role of the hypothalamic-pituitary-adrenal-gonadal axes (HPAGA) in the potential BA effect. Male AA and Wistar rats received subcutaneously BA or vehicle oil for 14 days. Hereafter followed a 1-week washout and consecutively a 3-week voluntary alcohol consumption period. The median (± median absolute deviation) voluntary ethanol consumption during the drinking period was higher in BA-treated than in control rats (4.94 ± 1.31 g/kg/day vs. 4.17 ± 0.31 g/kg/day, p = 0.07 and 1.01 ± 0.26 g/kg/day vs. 0.38 ± 0.27 g/kg/day, p = 0.05, for AA and Wistar rats, respectively; combined effect p < 0.01). The present results can explain the previous discrepancy between the two nandrolone studies. No significant BA effects on basal and ethanol-mediated serum testosterone and corticosterone levels were observed in blood samples taken at days 1, 8 and 22. However, 2h after ethanol administration significantly (p = 0.02) higher frequency of testosterone elevations was detected in high drinking AA rats compared to low drinking Wistars, which supports our previous hypotheses of a role of testosterone elevation in promoting ethanol drinking. Skin irritation and dermatitis were shown exclusively in the BA-treated animals. Altogether, the present results indicate that earlier findings obtained with Deca-Durabolin containing BA need to be re-evaluated.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Dividing Attention Lowers Children's but Increases Adults' False Memories

    ERIC Educational Resources Information Center

    Otgaar, Henry; Peters, Maarten; Howe, Mark L.

    2012-01-01

    The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a…

  18. Educating Older Adults about Their Increased Cancer Risk.

    ERIC Educational Resources Information Center

    Keintz, Martha K.; And Others

    1988-01-01

    The Cancer Program for Older Citizens is a program to improve the outcome of a possible cancer diagnosis for older adults by encouraging early detection of cancer. Program has achieved positive, though modest, changes in the cancer-related knowledge and beliefs of older adult participants, with these impacts sustained for months after the program.…

  19. Protection of chronic intermittent hypobaric hypoxia against collagen-induced arthritis in rat through increasing apoptosis.

    PubMed

    Shi, Min; Cui, Fang; Liu, Ai-Jing; Li, Jiao; Ma, Hui-Juan; Cheng, Ming; Yang, Jing; Zhang, Yi

    2011-04-25

    The aim of present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on collagen-induced arthritis (CIA) in rat. Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups: CIHH pre-treatment group (Pre-T), pre-control group (Pre-C), CIHH post-treatment group (Post-T), post-control group (Post-C) and blank control group (Con). The rats in Pre-T and Post-T groups were exposed to 28 d of hypobaric hypoxia (simulated 3 000 m altitude, 5 h per day, pO2 = 108.8 mmHg, 14% O2) in a hypobaric chamber before and 12 days after CIA induction, respectively. The rats in Pre-C and Post-C groups were only experienced CIA induction, being control groups for Pre-T and Post-T groups, respectively. The rats in Con group were not given any treatment. The thickness of two-hind paw of rat was measured with spiral micrometer and the degree of arthritis was evaluated by arthritis index (AI). Morphological changes of ankle joint were observed through HE staining. The apoptotic rate in synovial tissue was measured by terminal dUTP nick end labeling (TUNEL) and the apoptotic rate of CD3(+) T lymphocyte in spleen was measured by flow cytometry technique. The protein expressions of Bcl-2 and Bax were measured using immunohistochemistry SP method. The results showed that incidence rate of CIA in Pre-T rats was lower than that in Pre-C rats (P < 0.05). AI in Pre-T and Post-T rats were smaller than those in Pre-C and Post-C, respectively (P < 0.05). In Pre-C and Post-C rats, there were hyperplasia of synovial cell, pannus forming, infiltration with inflammatory cell, and destroyed cartilage and bone in ankle joint. On the contrary, pathological changes of ankle joint were alleviated significantly in Pre-T and Post-T rats. Compared with Pre-C and Post-C rats, apoptotic rates of synovial cell and T lymphocyte in Pre-T and Post-T rats were increased (P < 0.05). As to the possible anti-apoptosis mechanism, CIHH, no matter before and after CIA induction

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Cytochalasin inhibition of slow tension increase in rat aortic rings.

    PubMed

    Wright, G; Hurn, E

    1994-10-01

    We separated the K(+)-induced contraction of rat aortic rings into its initial (fast) and secondary (slow) components. It was found that temperature sensitivity, K+ depolarization, and Ca2+ dependency could each be utilized to differentiate between these two components of the contractile response. Increasing the passive tension preload of the tissue increased the fast response but had no significant effect on the secondary slow rise in tension. Cytochalasins, which inhibit actin polymerization, reversibly inhibited tension development by rat aortic rings with the effect selectively confined to the slow component of the K(+)-induced contraction. In a similar fashion, cytochalasin was shown to attenuate the slow tension increase caused by phorbol 12,13-dibutyrate. Finally, it was found that low concentrations of the protein kinase C (PKC) inhibitor staurosporine (8 x 10(-9) M) selectively attenuated the slow component of the K(+)-induced contraction. The results suggest that distinctly different mechanisms regulate the initial fast and secondary slow contractile responses induced by elevation of extracellular K+. Both mechanisms are voltage sensitive and use extracellular Ca2+. The fast but not the slow component was altered by changing the passive tension preload in a fashion consistent with a sliding filament mechanism of force development. The specific nature of the slow component is not certain but may involve low-level PKC activity and require the integrity and capability for remodeling of a specific portion of the actin-containing cytoskeleton.

  5. 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.

  6. Atorvastatin Increases Exercise Leg Blood Flow in Healthy Adults

    PubMed Central

    Parker, Beth A.; Capizzi, Jeffrey A.; Augeri, Amanda L.; Grimaldi, Adam S.; White, C. Michael; Thompson, Paul D.

    2011-01-01

    OBJECTIVES We sought to examine the effect of atorvastatin therapy on exercise leg blood flow in healthy middle-aged and older, men and women. BACKGROUND The vasodilatory response to exercise decreases in humans with aging and disease and this reduction may contribute to reduced exercise capacity. METHODS We used a double-blind, randomly assigned, placebo-controlled protocol to assess the effect of atorvastatin treatment on exercising leg hemodynamics. We measured femoral artery blood flow (FBF) using Doppler ultrasound and calculated femoral vascular conductance (FVC) from brachial mean arterial pressure (MAP) before and during single knee-extensor exercise in healthy adults (ages 40–71) before (PRE) and after (POST) 6 months of 80 mg atorvastatin (A: 14 men, 16 women) or placebo (P: 14 men, 22 women) treatment. FBF and FVC were normalized to exercise power output and estimated quadriceps muscle mass. RESULTS Atorvastatin reduced LDL cholesterol by approximately 50%, but not in the placebo group (p < 0.01). Atorvastatin also increased exercise FBF from 44.2 ± 19.0 to 51.4 ± 22.0 mL/min/W/kg muscle whereas FBF in the placebo group was unchanged (40.1 ± 16.0 vs 39.5 ± 16.1) (p <0.01). FVC also increased with atorvastatin from 0.5 ± 0.2 to. 0.6 ± 0.2 mL/min/mmHg/W/kg muscle, but not in the placebo subjects (P: 0.4 ± 0.2 vs 0.4 ± 0.2) ( p < 0.01). CONCLUSIONS High-dose atorvastatin augments exercising leg hyperemia. Statins may mitigate reductions in the exercise vasodilatory response in humans that are associated with aging and disease. PMID:22018642

  7. Increased Prevalence of Sleep-Disordered Breathing in Adults

    PubMed Central

    Peppard, Paul E.; Young, Terry; Barnet, Jodi H.; Palta, Mari; Hagen, Erika W.; Hla, Khin Mae

    2013-01-01

    Sleep-disordered breathing is a common disorder with a range of harmful sequelae. Obesity is a strong causal factor for sleep-disordered breathing, and because of the ongoing obesity epidemic, previous estimates of sleep-disordered breathing prevalence require updating. We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988–1994 and 2007–2010 using data from the Wisconsin Sleep Cohort Study, an ongoing community-based study that was established in 1988 with participants randomly selected from an employed population of Wisconsin adults. A total of 1,520 participants who were 30–70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing. Participants were invited for repeat studies at 4-year intervals. The prevalence of sleep-disordered breathing was modeled as a function of age, sex, and body mass index, and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey. The current prevalence estimates of moderate to severe sleep-disordered breathing (apnea-hypopnea index, measured as events/hour, ≥15) are 10% (95% confidence interval (CI): 7, 12) among 30–49-year-old men; 17% (95% CI: 15, 21) among 50–70-year-old men; 3% (95% CI: 2, 4) among 30–49-year-old women; and 9% (95% CI: 7, 11) among 50–70 year-old women. These estimated prevalence rates represent substantial increases over the last 2 decades (relative increases of between 14% and 55% depending on the subgroup). PMID:23589584

  8. Westernization of Chinese adults and increased subclinical atherosclerosis.

    PubMed

    Woo, K S; Chook, P; Raitakari, O T; McQuillan, B; Feng, J Z; Celermajer, D S

    1999-10-01

    Cardiovascular event rates are much lower in China compared with developed countries. "Westernization" of diet and lifestyle in the Chinese, however, may lead to an increased prevalence of atherosclerosis-related diseases. Because carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis, we examined IMT and vascular risk profile in community-based groups of rural Chinese, Westernized urban Chinese, and urban whites. Mean IMT of the common carotid artery was measured in 348 healthy adults, aged 42+/-13 years (range 21 to 71 years); 116 subjects from rural China, 116 urban Chinese subjects living in Hong Kong or in Australia, and 116 urban Caucasians living in Australia. These 3 groups were matched for age, sex, and cigarette smoke exposure. Urban Chinese subjects had slightly better risk factor profile (higher HDL-cholesterol and lower blood pressure) compared with rural Chinese subjects. Despite this, however, the mean IMT was lowest in rural Chinese (0.50+/-0.10 mm), intermediate in urban Chinese (0.56+/-0.12 mm), and highest in urban whites (0.64+/-0.13 mm) (P<0.001 for comparisons between all groups). These differences in IMT were not altered after adjustment for the major traditional cardiovascular risk factors (serum lipids, smoking, and blood pressure or for body mass index). The influence of vascular risk factors on atherosclerosis between urban versus rural Chinese subjects was studied by multivariate regression models and by comparing the steepness of regression slopes between risk factors and IMT in the subject groups. The effects of smoking, HDL-cholesterol, and triglycerides on IMT were significantly greater in the urban compared with the rural Chinese (P<0.01). These data suggest that Westernization of Chinese subjects is associated with greater susceptibility to the pro-atherogenic effects of traditional vascular risk factors, such as lipids and smoking, and with evidence of increased IMT as a marker of subclinical

  9. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies.

    PubMed

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

    1999-09-01

    The consequences of juvenile isolation and morphine treatment during the isolation period on (social) behaviour and mu-, delta- and kappa-opioid receptors in adulthood were investigated by using a social interaction test and in vitro autoradiography in rats. Juvenile isolation reduced social exploration in adults. Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats. Self-grooming and nonsocial exploration were enhanced after juvenile isolation. Morphine treatment had no effect on self-grooming, but suppressed nonsocial exploration in isolated rats. With respect to the opioid receptors, juvenile isolation resulted in regiospecific increases in mu-binding sites with a 58% increase in the basolateral amygdala and a 33% increase in the bed nucleus of stria terminalis. Morphine treatment in isolated rats reversed this upregulation in both areas. The number of delta-binding sites did not differ between the experimental groups. A general upregulation of kappa-binding sites was observed after juvenile isolation, predominantly in the cortical regions, the hippocampus and the substantia nigra. Morphine treatment did not affect the upregulation of kappa-receptors. The results show that juvenile isolation during the play period causes long-term effects on social and nonsocial behaviours and on the number of mu- and kappa- but not delta-opioid receptors in distinct brain areas. The number of mu-receptors in the basolateral amygdala appears to be negatively correlated with the amount of social exploration in adult rats.

  10. Increasing Access to Postsecondary Education for Adults in Rural Appalachia.

    ERIC Educational Resources Information Center

    Sullins, W. Robert; And Others

    1987-01-01

    Reports on a study of the barriers to adult participation in postsecondary education in the Appalachian regions of six southern states. Discusses policy-related, dispositional, situational, and institutional barriers to enrollment, and offers recommendations for reducing the obstacles. (DMM)

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.

    PubMed

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-05

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  16. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    NASA Astrophysics Data System (ADS)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  17. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    PubMed Central

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  18. Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

    PubMed

    Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

    2010-02-01

    Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood.

  19. 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

  20. 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

  1. Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

    PubMed Central

    O’Dell, Laura E.; Torres, Oscar V.; Natividad, Luis A.; Tejeda, Hugo A.

    2012-01-01

    Vulnerability to nicotine addiction is significantly increased in individuals who begin smoking during adolescence; however, the underlying mechanisms of this phenomenon remain unclear. This study examined the motivational effects of nicotine withdrawal in adolescent (PND 27–42) and adult (PND 60–75) rats using the conditioned place aversion paradigm. Male Wistar rats were tested for their initial preference for either of two distinct compartments of our conditioning apparatus. Rats were then implanted with subcutaneous (sc) pumps that produce equivalent blood plasma levels of nicotine for 14 days. Conditioning was conducted over the last 8 days of nicotine exposure. Rats received the nicotinic antagonist mecamylamine (1.5 or 3.0 mg/kg, sc) to precipitate withdrawal in their initially preferred compartment, and on alternate days they received saline in their non-preferred compartment. Following conditioning, rats were re-tested for their preference for each compartment. A subsequent study was conducted to examine potential developmental differences in learning place aversion produced by another aversive stimulus, lithium chloride (LiCl). Rats received LiCl (0, 10, 30, or 100 mg/kg, sc) in their initially preferred side using similar conditioning procedures. Adults displayed robust place aversion produced by nicotine withdrawal. This effect was lower in adolescent rats even in a group of young rats that received 7 additional days of nicotine exposure prior to conditioning. This developmental difference was specific to nicotine withdrawal since there were no differences between adolescents and adults in learning place aversion with LiCl. Our findings demonstrating reduced effects of nicotine withdrawal constitute a powerful basis for the increased vulnerability to nicotine dependence during adolescence. PMID:17184972

  2. 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

  3. 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

  4. Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

    PubMed Central

    Udoekwere, Ubong I.; Oza, Chintan S.

    2016-01-01

    Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with “poor” and “high weight support” groupings. A total of 35% of rats initially classified as “poor” were able to increase their weight-supported step measures to a level considered “high weight support” after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. SIGNIFICANCE STATEMENT Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal

  5. Modafinil increases histamine release in the anterior hypothalamus of rats.

    PubMed

    Ishizuka, Tomoko; Sakamoto, Yasuhiko; Sakurai, Toshimi; Yamatodani, Atsushi

    2003-03-20

    Modafinil, (RS)-2-(Diphenylmethylsulfinyl)acetamide, is a well known wake promoting drug used for the treatment of narcolepsy. We investigated the effect of modafinil on the hypothalamic histamine release in the anesthetized rat using in vivo microdialysis. Modafinil (150 mg/kg, i.p.) increased histamine release by 150% of the basal release. The intracerebroventricular (i.c.v.) injection of modafinil (1 nmol) also increased histamine release, however, when modafinil (1 nmol) was injected directly into the tuberomammillary nucleus, a limited region where cell bodies of the histaminergic neurons are located, histamine release was not altered. These observations suggest that modafinil may promote waking via the activation of the histaminergic system, although it does not appear to be a direct pharmacological target of modafinil.

  6. Royal Jelly Increases Collagen Production in Rat Skin After Ovariectomy

    PubMed Central

    Park, Hye Min; Cho, Min Hyoung; Cho, Yunhi

    2012-01-01

    Abstract Royal jelly (RJ) is a honeybee product that contains proteins, carbohydrates, fats, free amino acids, vitamins, and minerals. RJ has been reported to have antitumor, antibacterial, and wound-healing activities. We previously reported that RJ enhanced the migration of human dermal fibroblasts and altered the levels of cholesterol and sphinganine in an in vitro wound-healing model in addition to regulating skin photoaging following exposure to ultraviolet-B radiation. We established an animal model of skin aging in the context of estrogen deficiency and assessed the antiaging effects of RJ on skin. To establish an in vivo model of skin aging, bilateral ovariectomies were performed in 12-week-old virgin female Sprague-Dawley rats. Induction of osteoporosis was confirmed through two-dimensional images of the trabecular bone in the left femoral necks using microcomputed tomography. The protective effects of RJ ovariectomy-induced skin aging were examined by determining the protein expression of type I procollagen and matrix metalloproteinase (MMP)-1. The collagen content and epidermal thickness of skin tissue were measured by staining techniques. There was a significant difference in weight between sham-operated and ovariectomized groups. Food efficiency ratio did not differ significantly among the groups. The level of procollagen type I protein was increased in the dorsal skin of ovariectomized rats fed with a dietary supplement containing 1% RJ extract, but the level of MMP-1 was not altered. In particular, the amount of collagen recovered was close to the normal level. RJ may protect against skin aging by enhancing collagen production in rats with ovariectomy-induced estrogen deficiency. PMID:22468645

  7. Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

    PubMed Central

    2012-01-01

    Background There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown. Methods To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation. Results Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors. Conclusion Our results

  8. Increased apoptosis of lactotrophs in streptozotocin-induced diabetic rats is followed by increased proliferation.

    PubMed

    Arroba, Ana I; Lechuga-Sancho, Alfonso M; Frago, Laura M; Argente, Jesús; Chowen, Julie A

    2006-10-01

    Poorly controlled diabetes mellitus can result in decreased prolactin production and thus problems with lactation, reproduction, and other physiological processes. This may be due to a loss of lactotrophs, as we have previously shown that long-term (8 weeks) poorly controlled streptozotocin-induced diabetes results in increased death of lactotrophs and that this most likely occurs through the activation of caspase-8 and the extrinsic cell death cascade. However, cell proliferation is also increased in the anterior pituitary at this time, although the cell type undergoing this proliferation and whether it is a response to the increased cell death remains unknown. In order to determine the time-course of increased cell death and proliferation in the anterior pituitary and if this is related to changes in tumor necrosis factor (TNF)-alpha, a cytokine involved in the activation of the extrinsic cell death pathway, rats were killed at 1, 4, 6, and 8 weeks after the induction of diabetes. Cell death was significantly increased after 4 weeks, as was caspase-8 activation, although circulating levels of TNF-alpha were increased as early as 1 week. Pituitary levels of TNF-alpha did not change significantly until 8 weeks after diabetes onset. Similarly, Western-blot analysis of proliferating cell nuclear antigen showed that anterior pituitary cell proliferation increased significantly 8 weeks after diabetes onset, with the majority of proliferating cells, as detected by BrdU incorporation, corresponding to lactotrophs. These results suggest that the increased death of lactotrophs in poorly controlled diabetic rats is followed by increased proliferation of this cell type, even when no treatment is given.

  9. 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.

  10. 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.

  11. 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.

  12. Intermittent access to a sucrose solution for rats causes long-term increases in consumption.

    PubMed

    Eikelboom, Roelof; Hewitt, Randelle

    2016-10-15

    Intermittent access to palatable food can elevate consumption beyond an animal's immediate needs. If adult male rats (with ad lib access to food and water) are provided with a 4% sucrose solution, daily sucrose consumption is determined by the sucrose access schedule: access that is intermittent leads to high levels of consumption. In Experiment 1, sucrose solutions were first provided continuously or every second, third, or fourth day for 23.5h over 49days. Continuous-access sucrose consumption averaged 102g per day, while that for access every fourth day averaged 294g. Daily consumption averages for access every second and third day fell between these two extremes. When all rats were then given alternate-day access to sucrose for 24days in Phase II, the previously established consumption differences were maintained. Body weight was unaffected by sucrose access; rats adjusted their food consumption so that total calorie intake remained constant. In Experiment 2, compared to continuous 4% sucrose solution access, access every third day markedly elevated daily sucrose consumption after only four sucrose exposures. With this shorter Phase I, sucrose intake in the continuous group increased markedly when in Phase II all rats were given alternate day access. In Experiment 3, a lick-by-lick analysis of the difference in sucrose consumption between access every third day and continuous access revealed that all rats were consuming a similar number of sucrose meals; however, the meals were larger both in the first hour and over the whole 24h with intermittent access. This suggests a change in satiety as a mechanism underlying sucrose consumption difference.

  13. The Impact of Adult Vitamin D Deficiency on Behaviour and Brain Function in Male Sprague-Dawley Rats

    PubMed Central

    Turner, Karly M.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2013-01-01

    Background Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Methods Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. Results AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. Conclusions AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour. PMID:23951200

  14. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring.

  15. 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.

  16. Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Ryan, J L

    1984-12-01

    Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

  17. 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.

  18. 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

  19. 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.

  20. Compound Pollen Protein Nutrient Increases Serum Albumin in Cirrhotic Rats

    PubMed Central

    Shi, Hong Bo; Kong, Ming; Chen, Gong; Zhao, Jun; Shi, Hong Lin; Chen, Yu; Rowan, Frank G

    2010-01-01

    Background Malnutrition, especially protein-calorie malnutrition, is common in patients with liver cirrhosis. When in the status of malnutrition, the complications increase, liver function deteriorates, and the prognosis of patients with liver cirrhosis worsens. Hence, nutritional support and treatment is essential in patients with liver cirrhosis. Previous studies suggested that compound nutrition based on pollen can improve liver function, and can be a basic nutrient for patients with liver cirrhosis. However, the nutritional support based on pollen for malnutrition of cirrhotic patients needs to be further evaluated. In this study, we investigated the nutritional support of Noveliver, a new compound pollen protein nutrient, in the cirrhotic rats induced by carbon tetrachloride (CCl4). Methods The cirrhotic rats induced by CCl4 were treated with Noveliver in different doses, and treated with a regular compound pollen nutrient, untreated cirrhotic rats and normal rats were used as controls. Serum albumin were measured before and after the nutritional treatment in each group. At the same time, liver function, cytokines and pathological changes were also determined. Results In the second week of nutritional treatment, the levels of serum albumin in normal control group, low dose noveliver group, high dose noveliver group, compound protein pollen group and spontaneous recovery group were 35.67 ± 1.42, 33.07 ± 1.27, 32.27 ± 1.50, 30.53 ± 0.25, 24.53 ± 3.56 (g/L), respectively, the differences among the groups were significant (F = 14.007, P = 0.000); The levels of serum albumin in low dose Noveliver group, high dose Noveliver group and the compound protein pollen group were higher than that in the spontaneous recovery group (P = 0.000, 0.001, 0.003, respectively). In the second week of nutritional treatment, the serum levels of HGF in normal control group, low dose Noveliver group, high dose Noveliver group, compound protein pollen group and spontaneous recovery

  1. 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)

  2. 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.

  3. 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.

  4. Perinatal undernutrition facilitates morphine sensitization and cross-sensitization to cocaine in adult rats: a behavioral and neurochemical study.

    PubMed

    Velazquez, E E; Valdomero, A; Orsingher, O A; Cuadra, G R

    2010-01-20

    The development of sensitization to the locomotor effects of morphine and cross-sensitization between morphine and cocaine were evaluated in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 30 days of age (D-rats), and compared with well-nourished animals (C-rats). Dose-response curves to morphine-induced locomotor activity (5, 7.5, 10 or 15 mg/kg, i.p., every other day for 5 days) revealed a shift to the left in D-rats compared to C-rats. This implies that D-rats showed behavioral sensitization to the lower dose of morphine used (5 mg/kg), which was ineffective in C-rats. Furthermore, when a cocaine challenge (10 mg/kg, i.p) was given 48 h after the last morphine administration, only D-rats exhibited cross-sensitization in morphine-pretreated animals (7.5 and 10 mg/kg). In order to correlate the differential response observed with the functioning of the mesocorticolimbic dopaminergic system, extracellular dopamine (DA) levels were measured in the nucleus accumbens (core and shell) and the dorsal caudate-putamen. A challenge with cocaine in morphine pre-exposed animals produced an increase in DA release, but only in the nucleus accumbens "core" of D-rats. Similar DA levels were found in the nucleus accumbens "shell" and in the dorsal caudate-putamen of both groups. Finally, these results demonstrate that D-rats had a lower threshold for developing both a progressive behavioral sensitization to morphine and a cross-sensitization to cocaine. In accordance with these behavioral findings, a higher responsiveness of the nucleus accumbens core, expressed by increased DA levels, both basal and after cocaine challenge, was observed in D-rats.

  5. Increased incidence of adult pneumococcal pneumonia during school holiday periods

    PubMed Central

    Rodrigo, Chamira; Bewick, Thomas; Sheppard, Carmen; Greenwood, Sonia; McKeever, Tricia M.; Slack, Mary; Lim, Wei Shen

    2017-01-01

    Child contact is a recognised risk factor for adult pneumococcal disease. Peaks in invasive pneumococcal disease incidence observed during winter holidays may be related to changes in social dynamics. This analysis was conducted to examine adult pneumococcal community-acquired pneumonia (CAP) incidence during school holiday periods. Between September 2008 and 2013, consecutive adults admitted to hospitals covering the Greater Nottingham area with a diagnosis of CAP were studied. Pneumococcal pneumonia was detected using culture and antigen detection methods. Of 2221 adults studied, 575 (25.9%) were admitted during school holidays and 643 (29.0%) had pneumococcal CAP. CAP of pneumococcal aetiology was significantly more likely in adults admitted during school holidays compared to term time (35.3% versus 26.7%; adjusted OR 1.38, 95% CI 1.11–1.72, p=0.004). Over the 5-year period, the age-adjusted incidence of hospitalised pneumococcal CAP was higher during school holidays compared to term time (incident rate ratio 1.35, 95% CI 1.14–1.60, p<0.001); there was no difference in rates of all-cause CAP or non-pneumococcal CAP. Reported child contact was higher in individuals with pneumococcal CAP admitted during school holidays compared to term time (42.0% versus 33.7%, OR 1.43, 95% CI 1.00–2.03, p=0.046). Further study of transmission dynamics in relation to these findings and to identify appropriate intervention strategies is warranted. PMID:28326311

  6. Flavonoid Rutin Increases Thyroid Iodide Uptake in Rats

    PubMed Central

    Lima Gonçalves, Carlos Frederico; de Souza dos Santos, Maria Carolina; Ginabreda, Maria Gloria; Soares Fortunato, Rodrigo; Pires de Carvalho, Denise; Freitas Ferreira, Andrea Claudia

    2013-01-01

    Thyroid iodide uptake through the sodium-iodide symporter (NIS) is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO), the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH), and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function. PMID:24023911

  7. Flavonoid rutin increases thyroid iodide uptake in rats.

    PubMed

    Gonçalves, Carlos Frederico Lima; Lima Gonçalves, Carlos Frederico; Santos, Maria Carolina de Souza dos; de Souza dos Santos, Maria Carolina; Ginabreda, Maria Gloria; Fortunato, Rodrigo Soares; Soares Fortunato, Rodrigo; Carvalho, Denise Pires de; Pires de Carvalho, Denise; Freitas Ferreira, Andrea Claudia

    2013-01-01

    Thyroid iodide uptake through the sodium-iodide symporter (NIS) is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO), the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH), and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function.

  8. Increased regional vascular albumin permeation in the rat during anaphylaxis

    SciTech Connect

    Leng, W.; Chang, K.; Williamson, J.R.; Jakschik, B.A.

    1989-03-15

    The changes in vascular albumin permeation induced by systemic anaphylaxis were studied simultaneously in 21 different tissues of the same animal. Before Ag challenge sensitized rats were injected i.v. with 125I-albumin (test tracer), 51Cr-RBC (vascular space marker) and 57Co-EDTA (extravascular space marker). The index of vascular permeation used was the tissue to blood isotope ratio (tbir), which was obtained by dividing the ratio of 125I/51Cr counts in each tissue by the ratio of the same isotopes in the arterial blood sample. After Ag challenge, the increase in the tbir varied considerably among the different tissues. The most pronounced increase was noted in the lymph node (ninefold) followed by the aorta and mesentery (six- to sevenfold) and the various parts of the gastrointestinal tract (four- to sixfold). In the skin less than skeletal muscle less than lung less than liver and eye two- to fourfold increases occurred. Relatively minor increases in albumin permeation (less than twofold) were observed in the brain less than kidney less than heart and less than spleen. The testis was the only organ in which no significant change occurred. For some of the tissues there was also an increase in the tbir for 57Co/51Cr (an index of the extracellular fluid space) suggesting edema formation. The highest increase was noted in the aorta (fourfold). Minor increases occurred in the atrium of the heart, stomach, duodenum, and lymph nodes. There was also a 36% increase in hematocrit. Therefore, systemic anaphylaxis caused extensive extravasation of albumin and hemoconcentration.

  9. Combinatorial gene therapy renders increased survival in cirrhotic rats

    PubMed Central

    2010-01-01

    Background Liver fibrosis ranks as the second cause of death in México's productive-age population. This pathology is characterized by acummulation of fibrillar proteins in hepatic parenchyma causing synthetic and metabolic disfunction. Remotion of excessive fibrous proteins might result in benefit for subjects increasing survival index. The goal of this work was to find whether the already known therapeutical effect of human urokinase Plasminogen Activator and human Matrix Metalloprotease 8 extends survival index in cirrhotic animals. Methods Wistar rats (80 g) underwent chronic intoxication with CCl4: mineral oil for 8 weeks. Cirrhotic animals were injected with a combined dose of Ad-delta-huPA plus Ad-MMP8 (3 × 1011 and 1.5 × 1011 vp/Kg, respectively) or with Ad-beta-Gal (4.5 × 1011) and were killed after 2, 4, 6, 8 and 10 days. Then, liver and serum were collected. An additional set of cirrhotic animals injected with combined gene therapy was also monitored for their probability of survival. Results Only the cirrhotic animals treated with therapeutical genes (Ad-delta-huPA+Ad-MMP-8) showed improvement in liver fibrosis. These results correlated with hydroxyproline determinations. A significant decrement in alpha-SMA and TGF-beta1 gene expression was also observed. Cirrhotic rats treated with Ad-delta-huPA plus Ad-MMP8 had a higher probability of survival at 60 days with respect to Ad-beta-Gal-injected animals. Conclusion A single administration of Ad-delta-huPA plus Ad-MMP-8 is efficient to induce fibrosis regression and increase survival in experimental liver fibrosis. PMID:20509929

  10. 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.

  11. Acute uptake inhibition increases extracellular serotonin in the rat forebrain.

    PubMed

    Rutter, J J; Auerbach, S B

    1993-06-01

    The effect of acute uptake inhibition on serotonin (5-HT) in the rat central nervous system was monitored by using in vivo dialysis. Peripheral administration of the selective 5-HT uptake blocker, fluoxetine, caused a dose-dependent increase in extracellular 5-HT in both the diencephalon and the striatum. Administration of fluoxetine or sertraline, another selective 5-HT uptake inhibitor, caused a prolonged (24 hr) increase in 5-HT and decrease in 5-hydroxyindoleacetic acid. In addition, fluoxetine and sertraline attenuated the 5-HT releasing effect of fenfluramine administered 24 hr later. Local infusion of fluoxetine into the diencephalon caused an increase in 5-HT that was twice as large as the effect of peripheral injection. Peripheral fluoxetine, by enhancing extracellular 5-HT in the raphe, probably resulted in activation of somatodendritic autoreceptors and inhibition of 5-HT neuronal discharge. Thus, the increase in 5-HT in the diencephalon after peripheral fluoxetine presumably reflected a balance between decreased release and inhibition of reuptake. In support of this, after first infusing fluoxetine into the diencephalon to maximally block reuptake, peripheral injection of the uptake inhibitor caused a decrease in 5-HT.

  12. Traffic Noise Exposure Increases Gastric Pepsin Secretion in Rat.

    PubMed

    Moslehi, Azam; Nabavizadeh, Fatemeh; Keshavarz, Mansoor; Rouhbakhsh, Nematollah; Sotudeh, Masoud; Salimi, Ehsan; Barzegar Behrooz, Amir

    2016-03-01

    Noise is considered as one of the most severe sources of environmental and workplace constraints. Many noise effects are well known on immune function, hormonal levels, cardiovascular and respiratory systems. In this study, our aim is to evaluate the effects of traffic noise exposure on basal and stimulated gastric pepsin secretion. 48 male rats were exposed to traffic noise (86 dB) for a short term of (8h/day for 1 day) and a long term of (8h/day for 7, 14, 21 and 28 days) as well as a control group. The gastric contents were collected by the wash-out technique. Pepsin secretion was measured by employing the Anson method. Histological studies were carried out on the epithelial layer. The corticosteroid hormone was measured in the serum for the stress augmentation. The present finding indicated no changes in pepsin secretion content in the short term, but in the 14 and 21 days traffic noise exposure, basal gastric pepsin secretion increased markedly compared to the control group. Histological results showed that the number of oxyntic glands and cell nuclei decreased in comparison with the control group while the thickness of the epithelial layer increases. In addition, the corticosterone levels increase in all groups in comparison with the control. It seems that the increase of gastric pepsin secretion is due to the description and translation processes in the peptic cells and needs enough time for completion.

  13. Chronic exposure of adult rats to low doses of methylmercury induced a state of metabolic deficit in the somatosensory cortex.

    PubMed

    Kong, Hang-Kin; Wong, Ming-Hung; Chan, Hing-Man; Lo, Samuel Chun-Lap

    2013-11-01

    Because of the ever-increasing bioaccumulation of methylmercury (MeHg) in the marine food chain, human consumers are exposed to low doses of MeHg continually through seafood consumption. Epidemiological studies strongly suggest that chronic prenatal exposure to nanomolar of MeHg has immense negative impacts on neurological development in neonates. However, effects of chronic exposure to low doses (CELDs) of MeHg in adult brains on a molecular level are unknown. The current study aims to investigate the molecular effects of CELD of MeHg on adult somatosensory cortex in a rat model using proteomic techniques. Young adult rats were fed with a low dose of MeHg (40 μg/kg body weight/day) for a maximum of 12 weeks. Whole proteome expression of the somatosensory cortex (S1 area) of normal rats and those with CELD to MeHg were compared. Levels of MeHg, total calcium, adenosine triphosphate (ATP), and pyruvate were also measured. Comparative proteomic studies of the somatosensory cortexes revealed that 94 proteins involved in the various metabolic processes (including carbohydrate metabolism, generation of precursors for essential metabolites, energy, proteins, cellular components for morphogenesis, and neurotransmission) were down-regulated. Consequently, levels of important end products of active metabolism including ATP, pyruvate, and total calcium were also found to be significantly reduced concomitantly. Our results showed that CELD of MeHg induced a state of metabolic deficit in the somatosensory cortex of adult rats.

  14. Repeated administration of a synthetic cannabinoid receptor agonist differentially affects cortical and accumbal neuronal morphology in adolescent and adult rats

    PubMed Central

    Carvalho, A. F.; Reyes, B. A. S.; Ramalhosa, F.; Sousa, N.

    2014-01-01

    Recent studies demonstrate a differential trajectory for cannabinoid receptor expression in cortical and sub-cortical brain areas across postnatal development. In the present study, we sought to investigate whether chronic systemic exposure to a synthetic cannabinoid receptor agonist causes morphological changes in the structure of dendrites and dendritic spines in adolescent and adult pyramidal neurons in the medial prefrontal cortex (mPFC) and medium spiny neurons (MSN) in the nucleus accumbens (Acb). Following systemic administration of WIN 55,212-2 in adolescent (PN 37–40) and adult (P55–60) male rats, the neuronal architecture of pyramidal neurons and MSN was assessed using Golgi–Cox staining. While no structural changes were observed in WIN 55,212-2-treated adolescent subjects compared to control, exposure to WIN 55,212-2 significantly increased dendritic length, spine density and the number of dendritic branches in pyramidal neurons in the mPFC of adult subjects when compared to control and adolescent subjects. In the Acb, WIN 55,212-2 exposure significantly decreased dendritic length and number of branches in adult rat subjects while no changes were observed in the adolescent groups. In contrast, spine density was significantly decreased in both the adult and adolescent groups in the Acb. To determine whether regional developmental morphological changes translated into behavioral differences, WIN 55,212-2-induced aversion was evaluated in both groups using a conditioned place preference paradigm. In adult rats, WIN 55,212-2 administration readily induced conditioned place aversion as previously described. In contrast, adolescent rats did not exhibit aversion following WIN 55,212-2 exposure in the behavioral paradigm. The present results show that synthetic cannabinoid administration differentially impacts cortical and sub-cortical neuronal morphology in adult compared to adolescent subjects. Such differences may underlie the disparate development

  15. Increases in norepinephrine release and ovarian cyst formation during ageing in the rat

    PubMed Central

    Acuña, Eric; Fornes, Romina; Fernandois, Daniela; Garrido, Maritza P; Greiner, Monika; Lara, Hernan E; Paredes, Alfonso H

    2009-01-01

    . Conclusion These data suggest that the ageing process in the ovary of the Sprague-Dawley rat is accompanied by an increased sympathetic tone of the ovary. Consequently, this sympathetic change could be related to a neuroendocrine-driven formation of a polycystic condition similar to that observed in the sympathetic-activated adult ovary. PMID:19531218

  16. Identification of interneurons activated at different inclines during treadmill locomotion in adult rats.

    PubMed

    Tillakaratne, Niranjala J K; Duru, Paul; Fujino, Hidemi; Zhong, Hui; Xiao, Mei Si; Edgerton, V Reggie; Roy, Roland R

    2014-12-01

    By using c-fos as an activity-dependent marker, we identified the cholinergic interneurons around the central canal and lumbar interneurons throughout the gray matter that were activated after a 30-min bout of quadrupedal treadmill stepping at a 0° or 25° incline in adult rats. Increased loading (elevated treadmill incline) imposed during treadmill stepping activated more cholinergic interneurons in the proximity of the central canal, i.e., central canal cluster cells and partition neurons. Since cholinergic central canal cells are thought to modulate motoneuron excitability, these data suggest that increased load during stepping may increase motoneuronal activity through activating more cholinergic central canal cells. We identified the muscle-specific motoneurons and afferent terminals in the spinal cord by injecting cholera toxin subunit B in the soleus and tibialis anterior muscles. The number of interneurons in lumbar segments L4 (tibialis anterior) and L5 (soleus) was higher in both groups that stepped on the treadmill compared with control and was highest in rats that stepped at a 25° incline. In a majority of laminae, the distribution of total and muscle-specific activated interneurons was highest in the 25° incline group and lowest in the control group for both muscles. These data could reflect increased peripheral (proprioceptive) input as well as supraspinal drive associated with stepping and demonstrate the differences in 1) the activation of cholinergic interneurons near the central canal and 2) the laminar and segmental location of interneurons throughout the gray matter that play a role in generating stepping under different loading conditions in adult rats.

  17. Effect of light-dark changes on the locomotor activity in open field in adult rats and opossums.

    PubMed

    Klejbor, I; Ludkiewicz, B; Turlejski, K

    2013-11-01

    There have been no reports on how the light-dark changes determine the locomotor activity of animals in the group of high reactivity (HR) and low reactivity (LR). In the present study we have compared selected parameters of the locomotor activity of the HR and the LR groups of the laboratory opossums and Wistar rats during consecutive, light and dark phases in the open field test. Sixty male Wistar adult rats, at an average weight of 350 g each, and 24 adult Monodelphis opossums of both sexes at an average weight of 120 g each were used. The animals' activity for 2 h daily between the hours of 17:30 and 19:30, in line with the natural light-dark cycle were recorded and then analysed using VideoTrack ver.2.0 (Vievpoint France). According to our results, we noted that a change of the experimental conditions from light to dark involves an increase in the locomotor activity in rats and opossums of the HR group, while there is no effect on the activity of the rats and opossums in the LR group. Locomotor activity in the HR rats, both in the light and dark conditions is characterised by a consistent pattern of change - higher activity in the first stage of the recording and a slowdown (habituation) in the second phase of the observation. The locomotor activity of the opossum, during both light and dark conditions, was observed to be at a consistently high level compared to the rats.

  18. 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.

  19. 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.

  20. Effects of 5-fluorouracil on the thiamin status of adult female rats.

    PubMed

    Basu, T K; Aksoy, M; Dickerson, J W

    1979-01-01

    The effect of 5-fluorouracil on the thiamin status of normal female adult rats has been investigated. Pre-treatment of the animals with the cytotoxic drug daily for 3 successive days resulted in a significant decrease in hepatic concentrations of thiamin concomitant with a decrease in thiamin-dependent transketolase enzyme activity and an increase in thiamin-pyrophosphate-(TPP-)stimulating effect in whole blood when compared with those of pair-fed control animals. The TPP effect of transketolase enzyme activity was also increased by 5-fluorouracil in vitro. Furthermore, the treatment with 5-fluorouracil resulted in decreased liver and spleen concentrations without affecting the urinary excretory levels of thiamin in animals supplemented with large doses of the vitamin. Giving a dose comparable to a human therapeutic dose caused a similar increase in the TPP effect. These results indicate that treatment with 5-fluorouracil may be associated with thiamin deficiency by increasing either the utilization or the breakdown of thiamin.

  1. 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.

  2. 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.

  3. 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.

  4. California Adults Increase Fruit and Vegetable Consumption from 1997-2007

    ERIC Educational Resources Information Center

    Sugerman, Sharon; Foerster, Susan B.; Gregson, Jennifer; Linares, Amanda; Hudes, Mark

    2011-01-01

    Objective: To determine whether fruit and vegetable consumption among California adults significantly increased from 1997-2007. Design: Biennial telephone surveillance surveys of California adults' dietary practices. Participants: California adults (n = 9,105 total all 6 surveys). Intervention: Surveillance data reporting. Main Outcome Measures:…

  5. Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

    PubMed Central

    Eladl, Mohamed Ahmed; M Elsaed, Wael; Atef, Hoda; El-Sherbiny, Mohamed

    2017-01-01

    Background Several renal disorders affect the glomerular podocytes. Compensatory structural and functional changes have been observed in animals that have undergone unilateral renal ablation. These changes occur as a pliant response to quench the increased functional demand to maintain homeostasis of fluid and solutes. Nestin is an intermediate filament protein present in the glomerular podocytes of the adult kidney and is linked with the maintenance of its foot process structure. Structural changes in the podocytes ultimately restructure the filtration barrier. Very few studies related to the ultrastructural and histopathologic changes of the podocytes are documented. The present study aimed to assess the histopathologic changes at the ultrastructural level in the adapted kidney at different time intervals following unilateral renal ablation in adult rats and its relation with nestin. Methods Forty-eight rats were divided into four groups (n=12 in each group). The animals of Group A were control naïve rats, while the group B, group C and group D animals underwent left unilateral nephrectomy and the remaining right kidney was removed on days 10, 20 and 30, respectively. Each group included four sham-operated rats, which were sacrificed at the same time as the naïve rats. Each nephrectomized sample was weighed and its sections were subjected to hematoxylin and eosin examination, transmission electron microscopic study as well as immunostaining using the intermediate filament protein nestin. Results No difference was found between the kidney sections from the control group and the sham-operated groups. A significant increase in the weight of the right kidneys was noted in groups B, C and D (P<0.001). The ultrastructural adaptive changes seen in the glomeruli of group B were subsequently reduced in groups C and D. This finding corresponded to a similar pattern of nestin expression in the podocytes, which showed significant increase in group B followed by reduced

  6. Altered dendritic arborization of amygdala neurons in young adult rats orally intubated with Clitorea ternatea aqueous root extract.

    PubMed

    Rai, Kiranmai S; Murthy, K Dilip; Rao, Muddanna S; Karanth, K Sudhakar

    2005-07-01

    Young adult (60 day old) Wistar rats of either sex were orally intubated with 50 mg/kg body weight and 100 mg/kg body weight of aqueous root extract of Clitoria ternatea (CTR) for 30 days, along with age-matched saline controls. These rats were then subjected to passive avoidance tests and the results from these studies showed a significant increase in passive avoidance learning and retention. Subsequent to the passive avoidance tests, these rats were killed by decapitation. The amygdala was processed for Golgi staining and the stained neurons were traced using a camera lucida and analysed. The results showed a significant increase in dendritic intersections, branching points and dendritic processes arising from the soma of amygdaloid neurons in CTR treated rats especially in the 100 mg/kg group of rats, compared with age-matched saline controls. This improved dendritic arborization of amygdaloid neurons correlates with the increased passive avoidance learning and memory in the CTR treated rats as reported earlier. The results suggest that Clitoria ternatea aqueous root extract enhances memory by increasing the functional growth of neurons of the amygdala.

  7. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

  8. Increased alcohol consumption in rats after subchronic antidepressant treatment.

    PubMed

    Alén, Francisco; Orio, Laura; Gorriti, Miguel Á; de Heras, Raquel Gómez; Ramírez-López, María Teresa; Pozo, Miguel Ángel; de Fonseca, Fernando Rodríguez

    2013-09-01

    The use of antidepressants for alcoholism in humans has been a matter of controversy in recent years. Despite the existence of an important co-morbidity for depression and alcoholism, some studies suggest that the use of antidepressants could worsen the prognosis of alcoholism. However, there is a lack of studies in animal models exploring this phenomenon. In the present study, we show how the 15-d treatment with fluoxetine (10 mg/kg) or venlafaxine (50 mg/kg) affected alcohol deprivation effect (ADE) and subsequent alcohol consumption. Initially, fluoxetine reduced ADE and venlafaxine did not affect it. However, in the following days, both antidepressants increased alcohol consumption, an effect that was found to last at least 5 wk. Fluoxetine treatment was shown to cause a locomotor sensitized response to a challenge dose of amphetamine (0.5 mg/kg), indicating the presence of a supersensitive dopaminergic transmission. In summary, antidepressant treatment may increase alcohol consumption in rats after a period of alcohol deprivation and this could be related to alterations in the reward circuitry. This finding confirms in an animal model previous reports in humans that may limit the use of antidepressants for alcoholism.

  9. 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.

  10. Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

    PubMed

    Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

    2014-08-01

    Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.

  11. A role for the prefrontal cortex in heroin-seeking after forced abstinence by adult male rats but not adolescents.

    PubMed

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-02-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration.

  12. Hippocampal adult neurogenesis is enhanced by chronic eszopiclone treatment in rats.

    PubMed

    Methippara, Melvi; Bashir, Tariq; Suntsova, Natalia; Szymusiak, Ron; McGinty, Dennis

    2010-09-01

    The adult hippocampal dentate gyrus (DG) exhibits cell proliferation and neurogenesis throughout life. We examined the effects of daily administration of eszopiclone (Esz), a commonly used hypnotic drug and gamma-aminobutyric acid (GABA) agonist, compared with vehicle, on DG cell proliferation and neurogenesis, and on sleep-wake patterns. Esz was administered during the usual sleep period of rats, to mimic typical use in humans. Esz treatment for 7 days did not affect the rate of cell proliferation, as measured by 5-bromo-2'-deoxyuridine (BrdU) immunostaining. However, twice-daily Esz administration for 2 weeks increased survival of newborn cells by 46%. Most surviving cells exhibited a neuronal phenotype, identified as BrdU-neuronal nuclei (NeuN) double-labeling. NeuN is a marker of neurons. Non-rapid eye movement sleep was increased on day 1, but not on days 7 or 14 of Esz administration. Delta electroencephalogram activity was increased on days 1 and 7 of treatment, but not on day 14. There is evidence that enhancement of DG neurogenesis is a critical component of the effects of antidepressant treatments of major depressive disorder (MDD). Adult-born DG cells are responsive to GABAergic stimulation, which promotes cell maturation. The present study suggests that Esz, presumably acting as a GABA agonist, has pro-neurogenic effects in the adult DG. This result is consistent with evidence that Esz enhances the antidepressant treatment response of patients with MDD with insomnia.

  13. Differential Behavioral and Neurobiological Effects of Chronic Corticosterone Treatment in Adolescent and Adult Rats

    PubMed Central

    Li, Jitao; Xie, Xiaomeng; Li, Youhong; Liu, Xiao; Liao, Xuemei; Su, Yun-Ai; Si, Tianmei

    2017-01-01

    Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29–49) or adulthood (PND 71–91) and then subjected to behavioral testing or sacrifice for western blot analyses. Despite of similar physical and neuroendocrine effects in both age groups, chronic CORT treatment produced a series of behavioral and neurobiological effects with striking age differences. While CORT-treated adult animals exhibited decreased sucrose preference, increased anxiety levels and cognitive impairment, CORT-treated adolescent animals demonstrated increased sucrose preference, decreased anxiety levels, and increased sensorimotor gating functions. These differential behavioral alterations were accompanied by opposite changes in the two age groups in the expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylation of the obligatory subunit of the NMDA receptor, GluN1, and PSD-95 in rat hippocampus. These results suggest that prolonged glucocorticoid exposure during adolescence produces different behavioral and neurobiological effects from those in adulthood, which may be due to the complex interaction between glucocorticoids and the ongoing neurodevelopmental processes during this period. PMID:28210212

  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. Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats.

    PubMed

    Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Santos, Maria Augusta B dos; Tomaz, Débora B; Antunes, Altamir R; Scaini, Giselli; Morais, Meline O S; Streck, Emilio L; Quevedo, João

    2013-03-01

    Maternally deprived rats were treated with tianeptine (15 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming and open field tests. The BDNF, NGF and energy metabolism were assessed in the rat brain. Deprived rats increased the immobility time, but tianeptine reversed this effect and increased the swimming time; the BDNF levels were decreased in the amygdala of the deprived rats treated with saline and the BDNF levels were decreased in the nucleus accumbens within all groups; the NGF was found to have decreased in the hippocampus, amygdala and nucleus accumbens of the deprived rats; citrate synthase was increased in the hippocampus of non-deprived rats treated with tianeptine and the creatine kinase was decreased in the hippocampus and amygdala of the deprived rats; the mitochondrial complex I and II-III were inhibited, and tianeptine increased the mitochondrial complex II and IV in the hippocampus of the non-deprived rats; the succinate dehydrogenase was increased in the hippocampus of non-deprived rats treated with tianeptine. So, tianeptine showed antidepressant effects conducted on maternally deprived rats, and this can be attributed to its action on the neurochemical pathways related to depression.

  16. Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells

    PubMed Central

    Heino, Terhi J; Alm, Jessica J; Halkosaari, Heikki J; Välimäki, Ville-Valtteri

    2016-01-01

    Background and purpose Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (μCT), and histology. Results Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID:27196705

  17. Glutamate microinjection in the medial septum of rats decreases paradoxical sleep and increases slow wave sleep.

    PubMed

    Mukherjee, Didhiti; Kaushik, Mahesh K; Jaryal, Ashok Kumar; Kumar, Velayudhan Mohan; Mallick, Hruda Nanda

    2012-05-09

    The role of the medial septum in suppressing paradoxical sleep and promoting slow wave sleep was suggested on the basis of neurotoxic lesion studies. However, these conclusions need to be substantiated with further experiments, including chemical stimulation studies. In this report, the medial septum was stimulated in adult male rats by microinjection of L-glutamate. Sleep-wakefulness was electrophysiologically recorded, through chronically implanted electrodes, for 2 h before the injection and 4 h after the injection. There was a decrease in paradoxical sleep during the first hour and an increase in slow wave sleep during the second hour after the injection. The present findings not only supported the lesion studies but also showed that the major role of the medial septum is to suppress paradoxical sleep.

  18. Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat.

    PubMed

    Ibrahim, Marwa A A; Elbakry, Reda H; Bayomy, Naglaa A

    2016-02-01

    Bisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki-67, activated caspase-3 and estrogen receptor alpha (ER-α). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki-67 and caspase-3, but a non-significant increase in ER-α expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer.

  19. Juvenile stress potentiates aversive 22-kHz ultrasonic vocalizations and freezing during auditory fear conditioning in adult male rats.

    PubMed

    Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Wöhr, Markus

    2012-09-01

    Traumatic experiences that occur during adolescence can render individuals vulnerable to mood and anxiety disorders. A model in juvenile rats (age: 27-29 days) was developed previously to study the long-term effects of adolescent stress exposure on behaviour and physiology. This paradigm, termed juvenile stress, involves subjecting juvenile rats to different stressors on consecutive days over a 3-day period. Here, we investigated the effects of the juvenile stress paradigm on freezing behaviour and aversive 22-kHz ultrasonic vocalizations (USVs) during auditory fear conditioning in adult male rats (age: 68-90 days). We found that rats previously subjected to juvenile stress increased aversive 22-kHz USVs (total calls and time spent calling) compared with controls during fear-conditioning training. The acoustic USV parameters between control and juvenile stress rats were largely equivalent, including duration, peak frequency and amplitude. While rats did not differ in freezing behaviour during fear conditioning, juvenile stress rats exhibited greater cue-conditioned freezing upon testing 24 h later. Our results show that juvenile stress elicited different long-term changes in freezing and aversive USVs during fear conditioning. Furthermore, they highlight the importance of assessing USVs to detect experience-dependent differences between control and stress-exposed animals which are not detectable by measuring visible behaviour.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat

    PubMed Central

    Leroy, Claire; Pierre, Karin; Simpson, Ian A.; Pellerin, Luc; Vannucci, Susan J.; Nehlig, Astrid

    2013-01-01

    The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24 h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12 h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4 h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand. PMID:21624469

  5. Developmental differences in EEG and sleep responses to acute ethanol administration and its withdrawal (hangover) in adolescent and adult Wistar rats.

    PubMed

    Ehlers, Cindy L; Desikan, Anita; Wills, Derek N

    2013-12-01

    Age-related differences in sensitivity to the acute effects of alcohol may play an important role in the increased risk for the development of alcoholism seen in teens that begin drinking at an early age. The present study evaluated the acute and protracted (hangover) effects of ethanol in adolescent (P33-P40) and adult (P100-P107) Wistar rats, using the cortical electroencephalogram (EEG). Six minutes of EEG was recorded during waking, 15 min after administration of 0, 1.5, or 3.0 g/kg ethanol, and for 3 h at 20 h post ethanol, during the rats' next sleep cycle. Significantly higher overall frontal and parietal cortical power was seen in a wide range of EEG frequencies in adolescent rats as compared to adult rats in their waking EEG. Acute administration of ethanol did not produce differences between adolescents and adults on behavioral measures of acute intoxication. However, it did produce a significantly less intense acute EEG response to ethanol in the theta frequencies in parietal cortex in the adolescents as compared to the adults. At 20 h following acute ethanol administration, during the rats' next sleep cycle, a decrease in slow-wave frequencies (1-4 Hz) was seen and the adolescent rats were found to display more reduction in the slow-wave frequencies than the adults did. The present study found that adolescent rats, as compared to adults, demonstrate low sensitivity to acute ethanol administration in the theta frequencies and more susceptibility to disruption of slow-wave sleep during hangover. These studies may lend support to the idea that these traits may contribute to increased risk for alcohol use disorders seen in adults who begin drinking in their early teenage years.

  6. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    PubMed Central

    Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude

    2016-01-01

    Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187

  7. 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

  8. Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia

    PubMed Central

    Prieto-Lloret, Jesus; Ramirez, Maria; Olea, Elena; Moral-Sanz, Javier; Cogolludo, Angel; Castañeda, Javier; Yubero, Sara; Agapito, Teresa; Gomez-Niño, Angela; Rocher, Asuncion; Rigual, Ricardo; Obeso, Ana; Perez-Vizcaino, Francisco; González, Constancio

    2015-01-01

    Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55–60% O2 for the last 5–6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2-sensitivity of K+ currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life. Key points Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is

  9. THE CONSUMPTION OF RED PUPUNHA (BACTRIS GASIPAES KUNTH) INCREASES HDL CHOLESTEROL AND REDUCES WEIGHT GAIN OF LACTATING AND POST-LACTATING WISTAR RATS

    PubMed Central

    Carvalho, R. Piccolotto; Lemos, J.R. Gonzaga; de Aquino Sales, R. Souza; Martins, M. Gassen; Nascimento, C.H.; Bayona, M.; Marcon, J.L.; Monteiro, J. Barros

    2014-01-01

    Introduction The lactating and post-lactating periods are marked by large metabolic change. Production of milk is 60% lipid dependent. We reported in a recent scientific meeting that Red pupunha palm tree fruit increases HDL cholesterol in lactating rats. This study evaluated if consumption of Red Pupunha by adult female rats has a beneficial impact on the lipid metabolism of lacting and post-lacting adult rats. Objective Evaluate if consumption of red pupunha has a beneficial effect in the lipid metabolism of lacting and post-lacting adult Wistar rats. Research Methods Four groups including two for control; (1) control adult lactating rats, (2) control adults post-lactating rats; and two experimental groups; (3) pupunha adults lactating rats and (4) pupunha adult post-lactating rats were evaluated and compared regarding: weight gain, food consumption, plasma total protein, glucose, total lipid, triglycerides, total cholesterol and HDL-cholesterol levels. The mean difference and its 95% confidence intervals were used for group comparisons. Group comparisons were evaluated by using analysis of variance (one-way ANOVA). The statistical significance of the pairwise differences among groups was assessed by using the two-sided Tukey test. Results There were no important differences in food consumption, plasma glucose, total lipids and triglycerides among groups. The red pupunha lactating group gain less weight showing lower body mass index (BMI) than controls (p < 0.05). Total cholesterol was lower in red pupunha lactating than in controls but not in the red pupunha post-lactating group as compared to controls. Triglycerides were lower in the post-lactating red pupunha group as compared to the control group (p = 0.039) but not for the lactating groups. Red pupunha lactating and post-lactating groups had higher HDL-cholesterol than their corresponding control groups (p ≤ 0.01). Conclusion Original findings include the beneficial effect of red pupunha in post

  10. Learning under stress in the adult rat is differentially affected by 'juvenile' or 'adolescent' stress.

    PubMed

    Tsoory, Michael; Richter-Levin, Gal

    2006-12-01

    Epidemiological studies suggest that childhood trauma is associated with a predisposition to develop both mood and anxiety disorders, while trauma during adolescence is associated mainly with anxiety disorders. We studied in the rat the long-term consequences of 'juvenile' stress, namely stress experienced in a period in which substantial remodelling occurs across species in stress-sensitive brain areas involved in emotional and learning processing. In adulthood, 'juvenile' stressed rats exhibited reduced exploration in a novel setting, and poor avoidance learning, with 41% learning mainly to escape while 28% exhibited learned helplessness-like behaviours. In adult rats that underwent 'adolescent' stress, learned helplessness-like behaviours were not evident, although decreased exploration and poor avoidance learning were observed. This suggests that in the prepubertal phase juvenility may constitute a stress-sensitive period. The results suggest that juvenile stress induces lasting impairments in stress-coping responses. The 'juvenile' stress model presented here may be of relevance to individuals' reported predisposition to anxiety and depression following childhood trauma, and their increased susceptibility only to anxiety disorders following adolescent stress.

  11. Choline dietary supplementation improves LiCl-induced context aversion retention in adult rats.

    PubMed

    Moreno, Hayarelis C; Gil, Marta; Carias, Diamela; Gallo, Milagros; de Brugada, Isabel

    2012-06-25

    Previous studies have demonstrated that choline is an essential nutrient during prenatal and early postnatal developmental periods. Thus, the availability of choline during these periods produces some beneficial effects on hippocampal-dependent learning and memory in rats. However, research on the effect of adult choline supplementation on learning and memory abilities is scarce. In the present study, 3-4 month-old male Wistar rats receiving a 7-week choline-supplemented diet (4.5 fold that of a standard diet) and control rats receiving a standard diet were trained in a LiCl-induced contextual aversion task. Short and long-term context aversion retention was assessed by recording the consumption of a flavoured solution in the aversive and safe contexts over two subsequent tests. Statistical analysis showed that the supplemented group exhibited greater intake suppression in the aversive context than in the safe context when two retention tests were applied 3 and 15 days after conditioning. These results suggest that increasing dietary choline availability during adulthood may favour the retention of a context aversion.

  12. Protective effects of Peganum harmala extracts on thiourea-induced diseases in adult male rat.

    PubMed

    Hamden, Khaled; Masmoudi, Hatem; Ellouz, Feriel; ElFeki, Adelfatteh; Carreau, Serge

    2008-01-01

    Cancers and hepatoprotective prevention using traditional medicines have attracted increasing interest. The aim of our study was to characterize the putative protective effects of ethanol and chloroform extracts of Peganum harmala on thiourea-induced diseases in adult male rat. We seek to determine the effects of these plant extracts on body weight, thyroid and endocrine cancer parameters. In addition the putative hepatoprotective effect was checked by the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the bilirubin level in the blood. Our data show that ethanol and chloroform extracts of Peganum harmala protected the animal against the carcinogenic effects induced by thiourea since neuron-specific enolase (NSE) and thyroglobulin (TG) levels were back to the normal range. In addition, the observed-hepatocytotoxicity after thiourea treatment was greatly reduced (AST and ALT activities were respectively 270 IU/l and 60 IU/l and in the same order of magnitude as in the untreated rats) as well as the bilirubin levels (6 micromol/l) especially for animals receiving the choroform preparation. Therefore we may suggest that extracts of Peganum harmala are efficient to reduce the toxicity induced by thiourea in male rat as far as the above parameters are concerned.

  13. 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.

  14. Response of ependymal progenitors to spinal cord injury or enhanced physical activity in adult rat.

    PubMed

    Cizkova, Dasa; Nagyova, Miriam; Slovinska, Lucia; Novotna, Ivana; Radonak, Jozef; Cizek, Milan; Mechirova, Eva; Tomori, Zoltan; Hlucilova, Jana; Motlik, Jan; Sulla, Igor; Vanicky, Ivo

    2009-09-01

    Ependymal cells (EC) in the spinal cord central canal (CC) are believed to be responsible for the postnatal neurogenesis following pathological or stimulatory conditions. In this study, we have analyzed the proliferation of the CC ependymal progenitors in adult rats processed to compression SCI or enhanced physical activity. To label dividing cells, a single daily injection of Bromo-deoxyuridine (BrdU) was administered over a 14-day-survival period. Systematic quantification of BrdU-positive ependymal progenitors was performed by using stereological principles of systematic, random sampling, and optical Dissector software. The number of proliferating BrdU-labeled EC increased gradually with the time of survival after both paradigms, spinal cord injury, or increased physical activity. In the spinal cord injury group, we have found 4.9-fold (4 days), 7.1-fold (7 days), 4.9-fold (10 days), and 5.6-fold (14 days) increase of proliferating EC in the rostro-caudal regions, 4 mm away from the epicenter. In the second group subjected to enhanced physical activity by running wheel, we have observed 2.1-2.6 fold increase of dividing EC in the thoracic spinal cord segments at 4 and 7 days, but no significant progression at 10-14 days. Nestin was rapidly induced in the ependymal cells of the CC by 2-4 days and expression decreased by 7-14 days post-injury. Double immunohistochemistry showed that dividing cells adjacent to CC expressed astrocytic (GFAP, S100beta) or nestin markers at 14 days. These data demonstrate that SCI or enhanced physical activity in adult rats induces an endogenous ependymal cell response leading to increased proliferation and differentiation primarily into macroglia or cells with nestin phenotype.

  15. Nontraditional Student Engagement: Increasing Adult Student Success and Retention

    ERIC Educational Resources Information Center

    Wyatt, Linda G.

    2011-01-01

    Today, more than any other time in history, student demographics of college and university students in the United States are experiencing rapid and profound changes. Along with these increases in nontraditional student enrollment comes an increasing percentage of working nontraditional college students with a multitude of commitments that serve to…

  16. Sirolimus and tacrolimus rather than cyclosporine A cause bone loss in healthy adult male rats.

    PubMed

    Rubert, Mercedes; Montero, Mercedes; Guede, David; Caeiro, Jose-Ramón; Martín-Fernández, Marta; Díaz-Curiel, Manuel; de la Piedra, Concepción

    2015-06-01

    The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on bone mass, femoral microstructure, femoral biomechanical properties, and bone remodeling in healthy adult male rats. Forty-eight 5-month-old male Wistar rats were used. CsA (2 mg/kg/day), FK-506 (3 mg/kg/day), RAPA (1.25 mg/kg/day), or water (0.5 ml/rat/day, control group) were administered orally for 3 months. After sacrifice, mean values of immunosuppressants in blood were: CsA (670.4 ng/ml), FK-506 (19.2 ng/ml), and RAPA (4.8 ng/ml). Levels of biochemical parameters were normal in all groups. Femoral BMD was decreased in FK-506 and RAPA groups and lumbar BMD in FK-506 group. Trabecular volume fraction (BV/TV) decreased only in FK-506 group. RAPA and CsA affected femoral cortical structure, but FK-506 did not. FK-506 produced an increase in bone remodeling, and CsA a decrease. FK-506 group showed a decrease in biomechanical parameters relative to all groups. RAPA group showed a decrease in ultimate stress vs control group, and CsA group presented an increase in biomechanical parameters versus control group. We found that administration of both RAPA and FK-506 as monotherapy for healthy rats produced osteopenia. CsA treatment only produces slight damages in the cortical zone of the femur.

  17. Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning.

    PubMed

    Nobre, Jessica Lopes; Lisboa, Patricia Cristina; Lima, Natália da Silva; Franco, Juliana Gastão; Nogueira Neto, José Firmino; de Moura, Egberto Gaspar; de Oliveira, Elaine

    2012-04-01

    It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0·05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25-hydroxyvitamin D₃ (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition.

  18. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E

    2008-08-15

    In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle.

  19. Evaluation of amygdaloid neuronal dendritic arborization enhancing effect of Centella asiatica (Linn) fresh leaf extract in adult rats.

    PubMed

    Mohandas Rao, K G; Rao, Muddanna S; Rao, Gurumadhva S

    2012-12-03

    OBJECTIVE: Centella asiatica (CeA), a creeper, growing in moist places in India and other Asian countries. Leaves of CeA are used for memory enhancement in Ayurvedic system of medicine, an alternative system of medicine originated from India. In the present study, we have investigated the role of CeA fresh leaf extract treatment on adult rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. METHODS: Adult rats (2.5-month old) were fed with 2, 4 and 6 mL/(day kg) of fresh leaf extract of CeA for 2, 4 and 6 weeks. After the treatment period the rats were killed, brains were removed and amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Such silver impregnated amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with those of age matched control rats. RESULTS: The results showed a significant increase in the dendritic length (intersections) and dendritic branching points in amygdaloid neurons of the rats treated with higher dose [6 mL/(day·kg)] of CeA for longer period of time (i.e. 6 weeks). CONCLUSIONS: Constituents/active principles present CeA fresh leaf extract has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders.

  20. Quercetin accelerated cutaneous wound healing in rats by increasing levels of VEGF and TGF-β1.

    PubMed

    Gopalakrishnan, A; Ram, M; Kumawat, S; Tandan, Sk; Kumar, D

    2016-03-01

    Quercetin (3,3',4',5,7-penthydroxyflavone)-induced biological effects have been beneficial in various disease conditions. In this study, wound healing potential of quercetin was evaluated in a time-dependent manner in open excision wounds in adult Wistar rats. Experimentally-wounded rats were divided into two groups namely, control and quercetin-treated. Wounds were photographed and the area was measured on the day of wounding and on days 3, 7, 11 and 14 post-wounding. The granulation/healing tissue was collected on days 3, 7, 11 and 14 post-wounding for cytokine/growth factor measurements and histology/immunohistochemistry studies. There was significant time-dependent increase in wound closure in quercetin-treated rats. Vascular endothelial growth factor and transforming growth factor-β1 expressions were significantly upregulated in quercetin-treated rats, whereas tumor necrosis factor-α level was markedly reduced. Interleukin- 10 levels and CD31 stained vessels were markedly higher on day 3 and on day 7, respectively, in quercetin-treated rats. In H & E stained sections, quercetin-treated group showed less inflammatory cells, more fibroblast proliferation, increased microvessel density, better reepithelialization and more regular collagen deposition, as compared to control. The results suggest that topical application of quercetin promotes wound healing by effectively modulating the cytokines, growth factors and cells involved in inflammatory and proliferative phases of healing.

  1. Arrest in ciliated cell expansion on the bronchial lining of adult rats caused by chronic exposure to industrial noise.

    PubMed

    Oliveira, Maria João R; Pereira, António S; Ferreira, Paula G; Guimarães, Laura; Freitas, Diamantino; Carvalho, António P O; Grande, Nuno R; Aguas, Artur P

    2005-03-01

    Workers chronically exposed to high-intensity/low-frequency noise at textile plants show increased frequency of respiratory infections. This phenomenon prompted the herein investigation on the cytology of the bronchial epithelium of Wistar rats submitted to textile noise. Workplace noise from a cotton-mill room of a textile factory was recorded and reproduced in a sound-insulated animal room. The Wistar rats were submitted to a weekly schedule of noise treatment that was similar to that of the textile workers (8h/day, 5 days/week). Scanning electron microscopy (SEM) was used to compare the fine morphology of the inner surface of the bronchi in noise-exposed and control rats. SEM quantitative cytology revealed that exposure to noise for 5-7 months caused inhibition in the natural expansion of the area occupied by ciliated cells on the bronchial epithelium as adult rats grow older. This difference between noise-exposed and age-matched control rats was statistically significant (P<0.05) and documents that the cytology of the rat bronchial epithelium is mildly altered by noise exposure. The decrease in the area of bronchial cilia may impair the mucociliar clearance of the respiratory airways and, thus, increase vulnerability to respiratory infection.

  2. RYGB progressively increases avidity for a low-energy artificially sweetened diet in female rats

    PubMed Central

    Geary, Nori; Bächler, Thomas; Whiting, Lynda; Lutz, Thomas A.; Asarian, Lori

    2016-01-01

    Weight re-gain within 2 y after Roux-en-Y gastric bypass (RYGB) is significantly associated with increased intake of and cravings for sweet foods. Here we describe a novel model of this late increase in sweet appetite. Ovariectomized RYGB and Sham-operated rats, with or without estradiol treatment, were maintained on Ensure liquid diet and offered an artificially sweetened low-energy diet (ASD) 2 h/d. First, we tested rats more than six months after RYGB. ASD meals were larger in RYGB than Sham rats, whereas Ensure meals were smaller. General physical activity increased during ASD meals in RYGB rats, but not during Ensure meals. Second, new rats were adapted to ASD before surgery, and were then offered ASD again during 4–10 wk following surgery. Estradiol-treated RYGB rats lost the most weight and progressively increased ASD intake to >20 g/2 h in wk 9–10 vs. ~3 g/2 h in Sham rats. Finally, the same rats were then treated with leptin or saline for 8 d. Leptin did not affect body weight, Ensure intake, or activity during meals, but slightly reduced ASD intake in estradiol-treated RYGB rats. Food-anticipatory activity was increased in estradiol-treated RYGB rats during the saline-injection tests. Because increased meal-related physical activity together with larger meals is evidence of hunger in rats, these data suggest that (1) RYGB can increase hunger for a low-energy sweet food in rats and (2) low leptin levels contribute to this hunger, but are not its only cause. This provides a unique rat model for the increased avidity for sweets that is significantly associated with weight recidivism late after RYGB. PMID:26707654

  3. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats.

    PubMed

    Ellgren, Maria; Spano, Sabrina M; Hurd, Yasmin L

    2007-03-01

    Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 microg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 microg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 microg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

  4. Increased leukotriene B4 synthesis in immune injured rat glomeruli.

    PubMed Central

    Rahman, M A; Nakazawa, M; Emancipator, S N; Dunn, M J

    1988-01-01

    We examined glomerular synthesis of the 5-lipoxygenase metabolite, LTB4, in normal and immune-injured rat glomeruli. Glomeruli isolated from normal rats and from rats with nephrotoxic serum nephritis (NSN), passive Heymann nephritis (PHN) and cationic bovine gamma globulin (CBGG)-induced glomerulonephritis were incubated with the calcium ionophore A23187 (3 microM). Lipids in the glomeruli and media were extracted with ethyl acetate, and were purified and fractionated by HPLC. Immunoreactive-LTB4 (i-LTB4) was determined by radioimmunoassay on HPLC fractions with a detection limit of 50 pg of i-LTB4. A large peak of i-LTB4 that comigrated with authentic LTB4 was found exclusively in glomeruli isolated from the CBGG-injected rats. Addition of the lipoxygenase inhibitor BW755C (50 micrograms/ml) to glomerular incubation resulted in greater than 90% inhibition of i-LTB4. Synthesis of i-LTB4 by glomeruli from normal, NSN and PHN rats was undetectable. Glomerular LTB4 synthesis by CBGG-injected rats was confirmed by radiometric HPLC and by gas chromatography mass-spectroscopy (GC-MS) analysis. In order to rule out synthesis of LTB4 by neutrophils entrapped in the glomeruli, a group of rats received 1,000 rad total body x irradiation, with shielding of the kidneys before induction of CBGG glomerulonephritis. Despite greater than 95% reduction in total leukocyte count, glomerular synthesis of LTB4 remained enhanced. Augmented glomerular synthesis of the proinflammatory lipid, LTB4, in the CBGG model of glomerular disease could have an important role in the development of glomerular injury and proteinuria. Images PMID:2838526

  5. Betaine increases the butyrylcholinesterase activity in rat plasma.

    PubMed

    Šišková, K; Dubničková, M; Pašková, Ľ; Rajdl, D; Ďuračková, Z; Muchová, J; Pauliková, I; Racek, J

    2016-01-01

    The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; p<0.001 and 0.41+/-0.11 (B) vs. 0.22+/-0.04 (control) O.D./min/mg; p=0.001). In conclusion, betaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account.

  6. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats

    SciTech Connect

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-12-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 {mu}g/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor {beta} was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.

  7. Comparison of aortic intima and inner media in young adult versus aging rats. Stereology in a polarized system.

    PubMed Central

    Guyton, J. R.; Lindsay, K. L.; Dao, D. T.

    1983-01-01

    Age-related ultrastructural changes in the intima and inner media of rat thoracic aorta were examined by new morphometric techniques. Young adult male rats, 10 weeks old, were compared with 1-year-old male rats. The most marked changes were found in the sub-endothelium, which increased in thickness more than five-fold. Basement-membrane-like and granular material accounted for the bulk of this thickening. Certain other structures were increased sevenfold or more in subendothelium. These structures and the volume fractions they occupied in 1-year-old rats were as follows: banded collagen, 4.3%; mononuclear leukocytes, 4.5%; cystic structures, 3.3%; and fibrillar elastin, 1.0%. Changes were also demonstrated in the fenestrae of and at selected depth levels below the innermost, or alternatively the internal, elastic lamina. Collagen increased strikingly within fenestrae and just below the elastic lamina. This was associated with a 28% increase in the thickness of the elastic lamina and a recession of smooth muscle cytoplasm to a deeper position within the first musculoelastic medial layer. The alterations in subendothelial tissues imply an altered basis for mechanical support for aortic endothelium in aging rats. These results mark the successful application of micro-computer-based stereology to a situation of polarized geometry. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:6846504

  8. Increased CD147 and MMP-9 expression in the normal rat brain after gamma irradiation.

    PubMed

    Li, Hong; Wei, Ming; Li, Shenghui; Zhou, Ziwei; Xu, Desheng

    2013-01-01

    Radiation-induced vascular injury is a major complication of Gamma knife surgery (GKS). Previous studies have shown that CD147 and MMP-9 are closely associated with vascular remodeling and pathological angiogenesis. Thus, we analysed changes in CD147 and MMP-9 expression in the cerebral cortex to investigate the correlation between CD147 and MMP-9 in the rat following GKS. Adult male Wistar rats were subjected to GKS at a maximum dose of 75 Gy and then euthanized 1 to 12 weeks later. Using immunohistochemistry and western blot analysis, we found that CD147 and MMP-9 expression were markedly upregulated in the target area 8-12 weeks after GKS when compared with the control group. Immunofluorescent double staining demonstrated that CD147 signals colocalized with CD31, GFAP and MMP-9-positive cells. Importantly, CD147 levels correlated with increased MMP-9 expression in irradiated brain tissue. For the first time, these data demonstrate a potential relationship between CD147 and MMP-9 following GKS. In addition, our study also suggests that CD147 and MMP-9 may play a role in vascular injury after GKS.

  9. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect

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

    2011-09-15

    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 metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral

  10. Developmental effects of wheel running on hippocampal glutamate receptor expression in young and mature adult rats.

    PubMed

    Staples, M C; Somkuwar, S S; Mandyam, C D

    2015-10-01

    Recent evidence suggests that the behavioral benefits associated with voluntary wheel running in rodents may be due to modulation of glutamatergic transmission in the hippocampus, a brain region implicated in learning and memory. However, the expression of the glutamatergic ionotropic N-methyl-d-aspartate receptor (GluN) in the hippocampus in response to chronic sustained voluntary wheel running has not yet been investigated. Further, the developmental effects during young and mature adulthood on wheel running output and GluN expression in hippocampal subregions has not been determined, and therefore is the main focus of this investigation. Eight-week-old and 16-week-old male Wistar rats were housed in home cages with free access to running wheels and running output was monitored for 4weeks. Wheel access was terminated and tissues from the dorsal and ventral hippocampi were processed for Western blot analysis of GluN subunit expression. Young adult runners demonstrated an escalation in running output but this behavior was not evident in mature adult runners. In parallel, young adult runners demonstrated a significant increase in total GluN (1 and 2A) subunit expression in the dorsal hippocampus (DH), and an opposing effect in the ventral hippocampus (VH) compared to age-matched sedentary controls; these changes in total protein expression were not associated with significant alterations in the phosphorylation of the GluN subunits. In contrast, mature adult runners demonstrated a reduction in total GluN2A expression in the DH, without producing alterations in the VH compared to age-matched sedentary controls. In conclusion, differential running activity-mediated modulation of GluN subunit expression in the hippocampal subregions was revealed to be associated with developmental effects on running activity, which may contribute to altered hippocampal synaptic activity and behavioral outcomes in young and mature adult subjects.

  11. High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids

    PubMed Central

    Peirouvi, T.; Yekani, F.; Azarnia, M.; Massumi, M.

    2015-01-01

    Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic cerebrospinal fluid (E-CSF) including E13.5, E17-CSF and the adult cerebrospinal fluid (A-CSF), all extracted from rats. CSF samples were selected based on their effects on cell behavioral parameters. Primary cell culture was performed in the presence of either normal or high levels of KCL in a culture medium. High levels of KCL cause cell depolarization, and thus the activation of quiescent NSCs. Results from immunocytochemistry (ICC) and semi-quantitative RT-PCR (sRT-PCR) techniques showed that in E-CSF-treated groups, neuronal differentiation increased (E17>E13.5). In contrast, A-CSF decreased and increased neuronal and astroglial differentiations, respectively. Cell survivability and/or proliferation (S/P), evaluated by an MTT assay, increased by E13.5 CSF, but decreased by both E17 CSF and A-CSF. Based on the results, it is finally concluded that adult rat hippocampal proliferative cells are not restricted progenitors but rather show high plasticity in neuronal/astroglial differentiation according to the effects of CSF samples. In addition, using high concentrations of KCL in the primary cell culture led to an increase in the number of NSCs, which in turn resulted in the increase in neuronal or astroglial differentiations after CSF treatment. PMID:27175157

  12. The effects of perinatal tebuconazole exposure on adult neurological, immunological, and reproductive function in rats.

    PubMed

    Moser, V C; Barone, S; Smialowicz, R J; Harris, M W; Davis, B J; Overstreet, D; Mauney, M; Chapin, R E

    2001-08-01

    Studies are under way to address concerns of potential persistent immunotoxic, reproductive, and neurotoxic effects of perinatal exposure to several pesticides. Tebuconazole, a triazole fungicide, was evaluated as part of this project. Sprague-Dawley dams were administered tebuconazole (0, 6, 20, or 60 mg/kg) by oral gavage daily from gestational day 14 to postnatal day (PND)7; the pups were then dosed daily at the same levels from PND7-42. Separate groups of rats were used for testing of immunological parameters, neurobehavioral testing using a screening battery of functional tests, and cognitive evaluations. Other groups of rats were evaluated for reproductive development and function, while yet others were sacrificed at the end of the dosing period for histological analyses of major organs systems, including neuropathological assessments. Pup viability and body weight were decreased in the highest dose group. There were no differences in the fertility indices in the exposed rats mated as adults. In the sheep RBC-immunized high-dose rats, spleen weights and cellularity were increased, and the ratio of cell types was altered compared to controls. There were, however, no biologically significant changes in the immune function of these rats. At necropsy on PND46 or 152, kidney, liver, and spleen weights were altered by tebuconazole treatment, but a dose-response relationship was not clear for most organs; only decreased kidney and increased liver weights were consistent in both sexes. Histological analyses were generally unremarkable outside of the brain. One month after the end of dosing, acquisition of learning the platform location in a water tank (i.e., Morris water maze) was impaired in the high-dose group; there were no differences in neuromuscular ability, motor activity, or swim speed to account for this finding. Furthermore, there was no effect on recall of the position during a free-swim trial. Neuropathological evaluations revealed pyknotic cells across

  13. Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats.

    PubMed

    Lazzaretti, Camilla; Kincheski, Grasielle Clotildes; Pandolfo, Pablo; Krolow, Rachel; Toniazzo, Ana Paula; Arcego, Danusa Mar; Couto-Pereira, Natividade de Sá; Zeidán-Chuliá, Fares; Galvalisi, Martin; Costa, Gustavo; Scorza, Cecilia; Souza, Tadeu Mello E; Dalmaz, Carla

    2016-03-01

    Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.

  14. Prenatal nicotine exposure results in the myocardial fibrosis in the adult male offspring rats.

    PubMed

    Yu, Feng; Zheng, Aiqiang; Qian, Jin; Li, Yuexia; Wu, Lei; Yang, Jian; Gao, Xiren

    2016-09-01

    Our previous study showed that prenatal nicotine exposure could increase the heart rate of adult male offspring rats, but little is known about the mechanism. The aim of this study was to investigate the mechanism. Nicotine was subcutaneously administered to pregnant rats at a dose of 1.5mgkg(-1) from the gestational days 3-21; the control group received the same volume of saline by the same route. The offsprings' heart weight, ejection function, ultrastructure, and blood hormones were determined. The present study exhibited that prenatal nicotine exposure significantly decreased the offsprings' heart and body weight at gestational day 21 and at day 15 after birth, but had no effect on the heart and body weight at 90 days after birth. The hearts were fibrosed in the nicotine exposed male offsprings, and the heart ejection functions of the nicotine male offsprings at 90 days after birth were decreased, including SV, FS and EF. In addition, prenatal nicotine exposure significantly increased the offspring's blood adrenaline and norepinephrine levels. These data suggest that the increased heart rate caused by prenatal nicotine exposure may be a result of myocardial fibrosis, which leads to heart function decreases, and these data imply a myocardial fibrosis risk of prenatal nicotine exposure.

  15. Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy

    PubMed Central

    Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

    2016-01-01

    Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD. PMID:28035995

  16. Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

    PubMed Central

    Robertson, Donald; Rodger, Jennifer; Martin-Iverson, Mathew T.

    2016-01-01

    The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease. PMID:27936175

  17. Health reform in Massachusetts increased adult dental care use, particularly among the poor.

    PubMed

    Nasseh, Kamyar; Vujicic, Marko

    2013-09-01

    States frequently expand or limit dental benefits for adults covered by Medicaid. As part of statewide health reform in 2006, Massachusetts expanded dental benefits to all adults ages 19-64 whose annual income was at or below 100 percent of the federal poverty level. We examined the impact of this reform and found that it led to an increase in dental care use among the Massachusetts adult population, driven by gains among poor adults. Compared to the prereform period, dental care use increased by 2.9 percentage points among all nonelderly adults in Massachusetts, relative to all nonelderly adults in eight control states. For poor Massachusetts adults, the effect was larger-an eleven-percentage-point increase in dental care use above the increase among the state's nonpoor residents. The Massachusetts experience provides evidence that providing dental benefits to poor adults through Medicaid can improve dental care access and use. Our results imply that the lack of expanded dental coverage for low-income adults under the Affordable Care Act is a missed opportunity to improve access to oral care.

  18. Denervation of rat adrenal glands markedly increases preproenkephalin mRNA.

    PubMed Central

    Kilpatrick, D L; Howells, R D; Fleminger, G; Udenfriend, S

    1984-01-01

    The effect of denervation on the expression of rat adrenal proenkephalin has been examined. Following splanchnicectomy there was a several-fold increase in the steady-state levels of preproenkephalin mRNA, which became maximal after 24-48 hr (greater than 10-fold). These results indicate that the previously observed increase in rat adrenal enkephalin-containing peptides following denervation occurs entirely by a pretranslational mechanism. The increase in preproenkephalin mRNA was accompanied by a 50-75% decrease in rat adrenal poly(A)+ RNA. Neural input thus exerts a profound trophic influence on proenkephalin gene expression and RNA metabolism in rat adrenals. Images PMID:6594691

  19. Denervation of rat adrenal glands markedly increases preproenkephalin mRNA.

    PubMed

    Kilpatrick, D L; Howells, R D; Fleminger, G; Udenfriend, S

    1984-11-01

    The effect of denervation on the expression of rat adrenal proenkephalin has been examined. Following splanchnicectomy there was a several-fold increase in the steady-state levels of preproenkephalin mRNA, which became maximal after 24-48 hr (greater than 10-fold). These results indicate that the previously observed increase in rat adrenal enkephalin-containing peptides following denervation occurs entirely by a pretranslational mechanism. The increase in preproenkephalin mRNA was accompanied by a 50-75% decrease in rat adrenal poly(A)+ RNA. Neural input thus exerts a profound trophic influence on proenkephalin gene expression and RNA metabolism in rat adrenals.

  20. Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

    PubMed

    Mathew, Jobin; Paul, Jes; Nandhu, M S; Paulose, C S

    2010-09-01

    We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system.

  1. Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex.

    PubMed

    Geng, Kai-Wen; He, Ting; Wang, Rui-Rui; Li, Chun-Li; Luo, Wen-Jun; Wu, Fang-Fang; Wang, Yan; Li, Zhen; Lu, Yun-Fei; Guan, Su-Min; Chen, Jun

    2016-10-01

    Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether γ-aminobutyric acid A (GABAA) receptors are involved in mediating the ethanol effects, muscimol, a selective GABAA receptor agonist, or bicuculline, a selective GABAA receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABAA receptors in the mPFC of rats.

  2. 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.

  3. Chronic Δ9-Tetrahydrocannabinol during Adolescence Differentially Modulates Striatal CB1 Receptor Expression and the Acute and Chronic Effects on Learning in Adult Rats.

    PubMed

    Weed, Peter F; Filipeanu, Catalin M; Ketchum, Myles J; Winsauer, Peter J

    2016-01-01

    The purpose of this study was to determine whether chronic administration of Δ(9)-tetrahydrocannabinol (THC) during adolescence would (1) modify any sex-specific effects of THC on learning and (2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35-75, yielding four groups (female/saline, female/THC, male/saline, and male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32-18 mg/kg of THC acutely as adults (experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, female rats were more sensitive than male rats were to the rate-decreasing effects. Rats were then chronically administered 10 mg/kg of THC (experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than did rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males did. Western blot analysis of brain tissue indicated long-term changes in hippocampal and striatal cannabinoid type-1 receptor (CB1R) levels despite levels that were indistinguishable immediately after chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than male rats were to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC.

  4. ERK Is Involved in the Reorganization of Somatosensory Cortical Maps in Adult Rats Submitted to Hindlimb Unloading

    PubMed Central

    Dupont, Erwan; Stevens, Laurence; Cochon, Laetitia; Falempin, Maurice; Bastide, Bruno; Canu, Marie-Hélène

    2011-01-01

    Sensorimotor restriction by a 14-day period of hindlimb unloading (HU) in the adult rat induces a reorganization of topographic maps and receptive fields. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of intracellular MAPK signaling pathway since Extracellular-signal-Regulated Kinase 1/2 (ERK1/2) is known to play a significant role in the control of synaptic plasticity. In order to better understand the mechanisms underlying cortical plasticity in adult rats submitted to a sensorimotor restriction, we analyzed the time-course of ERK1/2 activation by immunoblot and of cortical reorganization by electrophysiological recordings, on rats submitted to hindlimb unloading over four weeks. Immunohistochemistry analysis provided evidence that ERK1/2 phosphorylation was increased in layer III neurons of the somatosensory cortex. This increase was transient, and parallel to the changes in hindpaw cortical map area (layer IV). By contrast, receptive fields were progressively enlarged from 7 to 28 days of hindlimb unloading. To determine whether ERK1/2 was involved in cortical remapping, we administered a specific ERK1/2 inhibitor (PD-98059) through osmotic mini-pump in rats hindlimb unloaded for 14 days. Results demonstrate that focal inhibition of ERK1/2 pathway prevents cortical reorganization, but had no effect on receptive fields. These results suggest that ERK1/2 plays a role in the induction of cortical plasticity during hindlimb unloading. PMID:21408155

  5. Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats.

    PubMed

    Choi, Y S; Sugano, M

    1988-01-01

    The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma-linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age.

  6. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  7. Dietary n-3 polyunsaturated fatty acids increase oxidative stress in rats with intracerebral hemorrhagic stroke.

    PubMed

    Park, Yongsoon; Nam, Somyoung; Yi, Hyeong-Joong; Hong, Hyun-Jong; Lee, Myoungsook

    2009-11-01

    Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.

  8. Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats.

    PubMed

    Aréchiga-Ceballos, F; Alvarez-Salas, E; Matamoros-Trejo, G; Amaya, M I; García-Luna, C; de Gortari, P

    2014-04-01

    Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the hypothalamus-pituitary-adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

  9. Interaction between the antioxidant activity of curcumin and cholinergic system on memory retention in adult male Wistar rats

    PubMed Central

    Sarlak, Zeynab; Oryan, Shahrbanoo; Moghaddasi, Mehrnoush

    2015-01-01

    Objective(s): The cholinergic system plays an important role in learning and memory. This study investigated the effects of curcumin (turmeric extract) and the cholinergic system and their interaction on memory retention of passive avoidance learning in adult male Wistar rats. Materials and Methods: At first, an injection cannula was implanted in right ventricles of the animals. One week after the surgery, the animals were trained with a shuttle box set up. Post-training, injections were performed in all experiments. Administration of curcumin increased memory retention. Also administrations of nicotine and pilocarpine, the cholinergic receptor agonists, increased memory retention, while it is decreased by succinylcholine and scopolamine, the cholinergic receptor antagonists. Then co-administration of curcumin and cholinergic drugs were performed. Intraperitoneal and intracerebroventricular injections were applied for the curcumin and cholinergic drugs, respectively. Results: Co-administration of curcumin (45 mg/kg) with a low dose of nicotine (0.1 µg/rat) or pilocarpine (0.5 µg/rat) increased memory retention significantly. Effects of succinylcholine (0.01, 0.1 and 0.5 µg/rat) or scopolamine (0.1, 1 and 5 µg/rat) were attenuated by curcumin markedly (45 mg/kg). Conclusion: The results suggest that curcumin has a close interaction with cholinergic system in memory retention process. PMID:26019804

  10. Substratum preferences of motor and sensory neurons in postnatal and adult rats.

    PubMed

    Gonzalez-Perez, Francisco; Alé, Albert; Santos, Daniel; Barwig, Christina; Freier, Thomas; Navarro, Xavier; Udina, Esther

    2016-02-01

    After peripheral nerve injuries, damaged axons can regenerate but functional recovery is limited by the specific reinnervation of targets. In this study we evaluated if motor and sensory neurites have a substrate preference for laminin and fibronectin in postnatal and adult stages. In postnatal dorsal root ganglia (DRG) explants, sensory neurons extended longer neurites on collagen matrices enriched with laminin (~50%) or fibronectin (~35%), whereas motoneurons extended longer neurites (~100%) in organotypic spinal cord slices embedded in fibronectin-enriched matrix. An increased percentage of parvalbumin-positive neurites (presumptive proprioceptive) vs. neurofilament-positive neurites was also found in DRG in fibronectin-enriched matrix. To test if the different preference of neurons for extracellular matrix components was maintained in vivo, these matrices were used to fill a chitosan guide to repair a 6-mm gap in the sciatic nerve of adult rats. However, the number of regenerating motor and sensory neurons after 1 month was similar between groups. Moreover, none of the retrotraced sensory neurons in DRG was positive for parvalbumin, suggesting that presumptive proprioceptive neurons had poor regenerative capabilities compared with other peripheral neurons. Using real-time PCR we evaluated the expression of α5β1 (receptor for fibronectin) and α7β1 integrin (receptor for laminin) in spinal cord and DRG 2 days after injury. Postnatal animals showed a higher increase of α5β1 integrin, whereas both integrins were similarly expressed in adult neurons. Therefore, we conclude that motor and sensory axons have a different substrate preference at early postnatal stages but this difference is lost in the adult.

  11. 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.

  12. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

  13. Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex

    PubMed Central

    Ruiz-Perera, L.; Muniz, M.; Vierci, G.; Bornia, N.; Baroncelli, L.; Sale, A.; Rossi, F.M.

    2015-01-01

    The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals. The molecular mechanisms underlying this effect remain largely unknown. Here, we explored fluoxetine effects on mouse visual cortical plasticity, and exploited a proteomic approach to identify possible candidates mediating the outcome of the antidepressant treatment on adult cortical plasticity. We showed that fluoxetine restores ocular dominance plasticity in the adult mouse visual cortex, and identified 31 differentially expressed protein spots in fluoxetine-treated animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by bioinformatics analysis revealed that these proteins are involved in the control of cytoskeleton organization, endocytosis, molecular transport, intracellular signaling, redox cellular state, metabolism and protein degradation. Altogether, these results indicate a complex effect of fluoxetine on neuronal signaling mechanisms potentially involved in restoring plasticity in the adult brain. PMID:26205348

  14. 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

  15. Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring.

    PubMed

    Harvey, Louise; Boksa, Patricia

    2014-08-01

    Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings

  16. Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

    PubMed

    Hill, Alexis S; Sahay, Amar; Hen, René

    2015-09-01

    Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.

  17. 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

  18. Regulation of molecular components of the synapse in the developing and adult rat superior cervical ganglion

    SciTech Connect

    Wu, K.; Black, I.B.

    1987-12-01

    Rat superior cervical sympathetic ganglion was used to begin studying the regulation of molecular components of the synapse. Ganglionic postsynaptic densities (PSDs) exhibited a thin, disc-shaped profile electron microscopically, comparable to that described for brain. Moreover, the presumptive ganglionic PSD protein (PSDp) was phosphorylated in the presence of Ca/sup 2 +/ and calmodulin, bound /sup 125/I-labeled calmodulin, and exhibited a M/sub r/ of 51,000 all characteristic of the major PSD protein of brain. These initial studies indicated that ganglionic PSDp and the major PSD protein of brain are comparable, allowing the study synaptic regulation in the well-defined superior cervical sympathetic ganglion. To obtain enough quantities of ganglionic PSDp, the authors used synaptic membrane fractions. During postnatal development, calmodulin binding to the ganglionic PSDp increased 411-fold per ganglion from birth to 60 days, whereas synaptic membrane protein increased only 4.5-fold. Consequently, different synaptic components apparently develop differently. Moreover, denervation of the superior cervical sympathetic ganglion in adult rats caused an 85% decrease in ganglionic PSDp-calmodulin binding, but denervation caused no change in synaptic membrane protein 2 weeks postoperatively. The observations suggest that presynaptic innervation selectively regulates specific molecular components of the postsynaptic membrane structure.

  19. Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function.

    PubMed

    Vinish, Monika; Elnabawi, Ahmed; Milstein, Jean A; Burke, Jesse S; Kallevang, Jonathan K; Turek, Kevin C; Lansink, Carien S; Merchenthaler, Istvan; Bailey, Aileen M; Kolb, Bryan; Cheer, Joseph F; Frost, Douglas O

    2013-08-01

    Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D₂ receptors; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28-49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D₁ receptor binding was reduced, D₂ binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients.

  20. Increased Risk Taking in Relation to Chronic Stress in Adults

    PubMed Central

    Ceccato, Smarandita; Kudielka, Brigitte M.; Schwieren, Christiane

    2016-01-01

    Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self-reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS). We additionally collected hair samples in a subsample of volunteers, in order to quantify accumulation of the stress hormone cortisol. We discovered a significant positive, though modest, correlation between self-reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations. PMID:26858663

  1. Different locomotor sensitization responses to repeated cocaine injections are associated with differential phosphorylation of GluA1 in the dorsomedial striatum of adult rats.

    PubMed

    Kim, Myonghwan; Kim, Wonju; Baik, Ja-Hyun; Yoon, Bong-June

    2013-11-15

    Behavioral sensitization to psychostimulants reflects neural adaptation, which might share a common mechanism with drug addiction. Outbred male rats show different locomotor sensitization responses to cocaine, and cocaine also produces varied addictive progress in humans. We investigated whether differences in the induction of sensitization would affect the long-term persistence of sensitized locomotor activity, and we sought to determine the molecular basis for the variability in sensitization. Male Sprague-Dawley rats that showed sensitized locomotor responses over 5 consecutive daily cocaine injections (SENS) had significantly lower initial locomotor responses to the 1st cocaine exposure than did rats that did not show locomotor sensitization (NONS). Furthermore, rats that underwent 1 month of cocaine withdrawal after 5 repeated cocaine injections also exhibited sensitized or non-sensitized locomotor responses to a challenge injection of cocaine (SENS-C or NONS-C, respectively). This variability was also related to the initial responsiveness to cocaine. We examined the level of phosphorylation of the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropioniate receptor (AMPAR) in the dorsal striatum and found that there were significant differences between the sensitized rats and the non-sensitized rats. pGluA1-Ser831 was increased in the SENS rats during the induction of locomotor sensitization, and pGluA1-Ser845 was increased in the SENS-C rats during the expression of locomotor sensitization. These phosphorylation changes were observed in the dorsomedial striatum (DMS) of adult rats but not in the dorsolateral striatum (DLS) of adults. Our findings suggest that differential phosphorylation of AMPAR might be an important mechanism that contributes to the development of locomotor sensitization to cocaine in adult rats.

  2. Effects of Increasing Task Load on Memory Impairment in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Oliver, Chris; Holland, Tony; Hall, Scott; Crayton, Lissa

    2005-01-01

    The effect of increasing the number of stimuli to be recalled was investigated to evaluate whether sensitivity for memory impairment was enhanced in adults with Down syndrome when using higher task load. Three levels of load were compared across three groups of adults: those with cognitive deterioration, no cognitive deterioration over age 40, and…

  3. Using the Natural Language Paradigm (NLP) to Increase Vocalizations of Older Adults with Cognitive Impairments

    ERIC Educational Resources Information Center

    LeBlanc, Linda A.; Geiger, Kaneen B.; Sautter, Rachael A.; Sidener, Tina M.

    2007-01-01

    The Natural Language Paradigm (NLP) has proven effective in increasing spontaneous verbalizations for children with autism. This study investigated the use of NLP with older adults with cognitive impairments served at a leisure-based adult day program for seniors. Three individuals with limited spontaneous use of functional language participated…

  4. Increasing risk awareness and facilitating safe sexual activity among older adults in senior housing.

    PubMed

    Gedin, Tonii C; Resnick, Barbara

    2014-01-01

    The prevalence of HIV in older adults is rising. This increase can be attributed to inconsistent condom use, low perceived disease susceptibility, and a sexual health knowledge gap found in older adults. Yet, little to no health promotion for older adults focuses on sex education. This study sought to determine the feasibility of a group-based educational program in senior housing settings and consider the utility of a self-efficacy based group education program on knowledge of disease risk and preventive techniques among older adults living in senior housing.

  5. 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.

  6. 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.

  7. Effect of genetically modified corn on the jejunal mucosa of adult male albino rat.

    PubMed

    Ibrahim, Marwa A A; Okasha, Ebtsam F

    2016-11-01

    Genetically modified (GM) plants expressing insecticidal traits offer a new strategy for crop protection. GM-corn contains Bacillus thuringiensis (Bt) genes producing delta endotoxins in the whole plant. Diet can influence the characteristics of the gastrointestinal tract altering its function and structure. The aim of this study was to evaluate the effect of GM-corn on the histological structure of jejunal mucosa of adult male albino rat using different histological, immunohistochemical and morphometrical methods. Twenty adult male albino rats were divided into two equal groups; control and GM-corn fed group administered with 30% GM-corn for 90days. Specimens from the jejunum were processed for light and electron microscopy. Immunohistochemical study was carried out using antibody against proliferating cell nuclear antigen (PCNA). Different morphometrical parameters were assessed. Specimens from GM-corn fed group showed different forms of structural changes. Focal destruction and loss of the villi leaving denuded mucosal surface alternating with stratified areas were observed, while some crypts appeared totally disrupted. Congested blood capillaries and focal infiltration with mononuclear cells were detected. Significant upregulation of PCNA expression, increase in number of goblet cells and a significant increase in both villous height and crypt depth were detected. Marked ultrastructural changes of some enterocytes with focal loss of the microvillous border were observed. Some enterocytes had vacuolated cytoplasm, swollen mitochondria with disrupted cristae and dilated rough endoplasmic reticulum (rER). Some cells had dark irregular nuclei with abnormally clumped chromatin. It could be concluded that consumption of GM-corn profoundly alters the jejunal histological structure.

  8. Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats.

    PubMed

    Alway, Stephen E; Degens, Hans; Lowe, Dawn A; Krishnamurthy, Gururaj

    2002-02-01

    The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 x Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were approximately 275-650% (P < 0.001) and approximately 500-1,100% (P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were approximately 300-900% greater in fast and slow muscles of aged animals (P < or = 0.02), and Mist 1 mRNA was approximately 50% greater in the plantaris and gastrocnemius muscles (P < 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were approximately 17-740% greater (P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

  9. Hypothyroidism in the Adult Rat Causes Incremental Changes in Brain-Derived Neurotrophic Factor, Neuronal and Astrocyte Apoptosis, Gliosis, and Deterioration of Postsynaptic Density

    PubMed Central

    Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J.; Bueno, Susan M.; Gonzalez, Pablo A.; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P.; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M.

    2012-01-01

    Background Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T4) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism. Methods Adult male Sprague-Dawley rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus of control and hypothyroid adult rats by confocal microscopy. The content of brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl-d-aspartate receptor (NMDAr) were analyzed by immunoblot. Results : We observed that the hippocampus of hypothyroid adult rats displayed increased apoptosis levels in neurons and astrocyte and reactive gliosis compared with controls. Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at the PSD of the CA3 region of hypothyroid rats, compared with controls. We also observed that the glutamatergic synapses from the stratum radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. This observation was in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid animals. Conclusions Our data suggest that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of PSD, reduces neuronal and astrocyte survival, and alters the content of the signaling neurotrophic factors, such as BDNF. PMID:22870949

  10. Effect of age increase on metabolism and toxicity of ethanol in female rats.

    PubMed

    Kim, Young C; Kim, Sung Y; Sohn, Young R

    2003-12-12

    Age-dependent change in the effects of acute ethanol administration on female rat liver was investigated. Female Sprague-Dawley rats, each aged 4, 12, or 50 weeks, received ethanol (2 g/kg) via a catheter inserted into a jugular vein. Ethanol elimination rate (EER), most rapid in the 4 weeks old rats, was decreased as the age advanced. Hepatic alcohol dehydrogenase activity was not altered by age, but microsomal p-nitrophenol hydroxylase activity was significantly greater in the 4 weeks old rats. Relative liver weight decreased with age increase in proportion to reduction of EER. Hepatic triglyceride and malondialdehyde concentrations increased spontaneously in the 50 weeks old nai;ve rats. Ethanol administration (3 g/kg, ip) elevated malondialdehyde and triglyceride contents only in the 4 and the 12 weeks old rats. Hepatic glutathione concentration was increasingly reduced by ethanol with age increase. Ethanol decreased cysteine concentration in the 4 weeks old rats, but elevated it significantly in the older rats. Inhibition of gamma-glutamylcysteine synthetase activity by ethanol was greater with age increase, which appeared to be responsible for the increase in hepatic cysteine. The results indicate that age does not affect the ethanol metabolizing capacity of female rat liver, but the overall ethanol metabolism is decreased in accordance with the reduction of relative liver size. Accordingly induction of acute alcoholic fatty liver is less significant in the old rats. However, progressively greater depletion of glutathione by ethanol in older rats suggests that susceptibility of liver to oxidative damage would be increased as animals grow old.

  11. Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats.

    PubMed

    Fırat, Uğur; Kaya, Savaş; Cim, Abdullah; Büyükbayram, Hüseyin; Gökalp, Osman; Dal, Mehmet Sinan; Tamer, Mehmet Numan

    2012-01-01

    Eryptosis is a term to define apoptosis of erythrocytes. Oxidative stress and hyperglycemia, both of which exist in the diabetic intravascular environment, can trigger eryptosis of erythrocytes. In this experimental study, it is presented that the majority of erythrocytes shows caspase-3 immunoreactivity in streptozocin- (STZ)-induced diabetic rats. Besides that, caspase-3 positive erythrocytes are aggregated and attached to vascular endothelium. In conclusion, these results may start a debate that eryptosis could have a role in the diabetic complications.

  12. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    SciTech Connect

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-11-15

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  13. Long-term exposure to a ‘safe’ dose of bisphenol A reduced protein acetylation in adult rat testes

    PubMed Central

    Chen, Zhuo; Zuo, Xuezhi; He, Dongliang; Ding, Shibin; Xu, Fangyi; Yang, Huiqin; Jin, Xin; Fan, Ying; Ying, Li; Tian, Chong; Ying, Chenjiang

    2017-01-01

    Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1. PMID:28067316

  14. Long-term exposure to a ‘safe’ dose of bisphenol A reduced protein acetylation in adult rat testes

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Zuo, Xuezhi; He, Dongliang; Ding, Shibin; Xu, Fangyi; Yang, Huiqin; Jin, Xin; Fan, Ying; Ying, Li; Tian, Chong; Ying, Chenjiang

    2017-01-01

    Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1.

  15. Estrogen normalizes perinatal nicotine-induced hypertensive responses in adult female rat offspring.

    PubMed

    Xiao, Daliao; Huang, Xiaohui; Yang, Shumei; Zhang, Lubo

    2013-06-01

    Perinatal nicotine exposure caused a sex-dependent heightened vascular response to angiotensin II (Ang II) and increased blood pressure in adult male but not in female rat offspring. The present study tested the hypothesis that estrogen normalizes perinatal nicotine-induced hypertensive response to Ang II in female offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. Ovariectomy and 17β-estradiol replacement were performed on 8-week-old female offspring. At 5 months of age, Ang II-induced blood pressure responses were not changed by nicotine treatment in the sham groups. In contrast, nicotine significantly enhanced Ang II-induced blood pressure responses as compared with saline control in the ovariectomy groups, which was associated with increased Ang II-induced vascular contractions. These heightened responses were abrogated by 17β-estradiol replacement. In addition, nicotine enhanced Ang II receptor type I, NADPH (nicotinamide adenine dinucleotide phosphate) oxidase type 2 protein expressions, and reactive oxygen species production of aortas as compared with saline control in the ovariectomy groups. Antioxidative agents, both apocynin and tempol, inhibited Ang II-induced vascular contraction and eliminated the differences of contractions between nicotine-treated and control ovariectomy rats. These findings support a key role of estrogen in the sex difference of perinatal nicotine-induced programming of vascular dysfunction, and suggest that estrogen may counteract heightened reactive oxygen species production, leading to protection of females from development programming of hypertensive phenotype in adulthood.

  16. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    PubMed

    Iguchi, Yoshio; Kosugi, Sakurako; Nishikawa, Hiromi; Lin, Ziqiao; Minabe, Yoshio; Toda, Shigenobu

    2014-01-01

    Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  17. Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

    PubMed Central

    Li, Dongpeng; Ma, Shanshan; Guo, Dewei; Cheng, Tian; Li, Hongwei; Tian, Yi; Li, Jianbin; Guan, Fangxia; Yang, Bo; Wang, Jian

    2016-01-01

    Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague–Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID:26886755

  18. Protective effect of vitamin E on methyl methanesulfonate-induced teratozoospermia in adult Sprague-Dawley rats.

    PubMed

    Tang, Zhian; Ding, Weiliang; Wang, Lun; Jiang, Wenchu; Zhang, Quanxiang; Chen, Hong; Zou, Hongnan; Dong, Yongkang; Shao, Jianwei; Ma, Tieliang

    2015-09-01

    The protective effect of vitamin E (VE, α-tocopherol) on methyl methanesulfonate (MMS)-induced teratozoospermia was investigated in adult rats. Rats (n=6 per group) were divided into three groups: i) Control group, treated with distilled water from days 1 to 5; ii) the MMS group, treated with MMS at a dose of 40 mg·kg(-1) from days 1‑5; or iii) the VE+MMS group, treated with MMS at a dose of 40 mg·kg(-1) from days 1‑5, followed by VE at a dose of 150 mg·kg(-1) from day 6 for 6 weeks. Sperm count, motility and morphology were examined following treatment with VE. The serum testosterone level and antioxidant enzyme activity were measured, and the localization of Vasa, promyelocytic leukemia zinc finger protein (Plzf) and synaptonemal complex protein 3 (Scp3) were also examined. MMS treatment decreased sperm count and motility, and the levels of immunoreactive serum testosterone and endogenous antioxidants. In addition, MMS increased the percentage of abnormal sperm and the levels of free radicals. After MMS and VE treatment, sperm count and motility were significantly higher in rats from the VE+MMS group than in the MMS group. In addition, the serum testosterone concentration, as well as the levels of Vasa and free radicals and the percentage of abnormal sperm, decreased. The results indicated that VE has protective effects against MMS-induced teratozoospermia in adult rats.

  19. Influence of 50 Hz magnetic field on sex hormones and other fertility parameters of adult male rats.

    PubMed

    Al-Akhras, Moh'd-Ali; Darmani, Homa; Elbetieha, Ahmed

    2006-02-01

    The effects of an extremely low frequency (ELF) magnetic field on the sex hormones and other fertility parameters of adult male Sprague-Dawley rats were investigated. Adult male rats were exposed to a 50 Hz sinusoidal magnetic field at approximately 25 microT (rms) for 18 consecutive weeks. There were no significant effects on the absolute body weight and the weight of the testes of the exposed rats. However, the weights of seminal vesicles and preputial glands were significantly reduced in the exposed male rats. Similarly, a significant reduction in sperm count was observed in the exposed group. Furthermore, there were no significant effects on the serum levels of male follicle stimulating hormone (FSH) during the 18 weeks of exposure period. On the other hand, there was a significant increase in the serum levels of male luteinizing hormone (LH) after 18 weeks of exposure (P < .005), while testosterone levels were significantly decreased only after 6 and 12 weeks of the exposure period. These results suggest that long term exposure to ELF could have adverse effects on mammalian fertility and reproduction.

  20. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    PubMed Central

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

  1. Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress.

    PubMed

    Gomez, Francisca; García-García, Luis

    2017-02-01

    Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35d-old) male rats, the stress-like effects induced by short-term (3d-4d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60-65d-old) to a similar FLX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses. We show that FLX acutely increased plasma corticosterone concentrations while it attenuated the stress-induced-hyperthermia (SIH) as well as it reduced (≈40%) basal POMC mRNA expression in the arcuate nucleus (ARC). However, FLX did not alter the basal expression of PVN-corticotrophin-releasing hormone (CRH), anterior pituitary-pro-opiomelanocortin (POMC) and raphe nucleusserotonin transporter (SERT). Nonetheless, some regressions point towards the plausibility that FLX activated the hypothalamic-pituitary-adrenal (HPA). The behavioral study revealed that FLX acutely increased emotional reactivity in the holeboard, effect followed by a body weight loss of ≈2.5% after 24h. Interestingly, i.p. injection with vehicle did not have behavioral effects, furthermore, after experiencing the stressful component of the holeboard, the rats kept eating and gaining weight as normal. By contrast, the stress-naïve rats reduced food intake and gained less weight although maintaining a positive energy state. Therefore, on one hand, repetition of a mild stressor would unchain compensatory mechanisms to restore energy homeostasis after stress increasing the resiliency to novel stressors. On the other hand, FLX might render stressed adult rats vulnerable to novel stressors through the emergence of counter-regulatory changes, involving HPA axis activation and diminished sympathetic output

  2. 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

  3. The H1 histamine receptor blocker, chlorpheniramine, completely prevents the increase in REM sleep induced by immobilization stress in rats.

    PubMed

    Rojas-Zamorano, J A; Esqueda-Leon, E; Jimenez-Anguiano, A; Cintra-McGlone, L; Mendoza Melendez, M A; Velazquez Moctezuma, J

    2009-01-01

    Chlorpheniramine is a selective antagonist of the H1 histaminergic receptor subtype and its effects in humans include somnolence. Chlorpheniramine affects sleep in rats, mainly by decreasing REM sleep. On the other hand, stress by immobilization induces an important increase in the percentage of REM sleep. In this study we analyzed the effects of blocking histaminergic receptors on REM sleep induced by immobilization stress. Adult male Wistar rats were chronically implanted for sleep recording. Immobilization stress was induced by placing the rat in a small cylinder for 2 h. Experimental conditions were: A. Control; B. Stress; C. Stress plus vehicle and D. Stress plus chlorpheniramine. Independent experiments were done both in the dark, as well as the light period. Results showed that the increase in REM sleep observed after immobilization stress was completely abolished by chlorpheniramine, both in the dark and in the light phase. Furthermore, the decrease in REM sleep was significant even when compared to the non-stressed control rats. REM sleep latency was also significantly longer during both light phases. The present results suggest that REM sleep is quite sensitive to histaminergic blockage. It is possible that chlorpheniramine is also blocking the cholinergic mechanisms generating REM sleep.

  4. 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.

  5. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    PubMed

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO.

  6. Amantadine improves cognitive outcome and increases neuronal survival after fluid percussion traumatic brain injury in rats.

    PubMed

    Wang, Tao; Huang, Xian-Jian; Van, Ken C; Went, Gregory T; Nguyen, Jack T; Lyeth, Bruce G

    2014-02-15

    This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day. Terminal blood draws were obtained from TBI rats at the time of euthanasia at varying time points after the last amantadine dose. Pharmacokinetics analysis confirmed that the doses of AMT achieved serum concentrations similar to those observed in humans receiving therapeutic doses (100-400 mg/day). Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 12-16 after TBI. Brain tissues were collected and stained with Cresyl-violet for long-term cell survival analysis. Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI.

  7. Testosterone induces an intracellular calcium increase by a nongenomic mechanism in cultured rat cardiac myocytes.

    PubMed

    Vicencio, Jose Miguel; Ibarra, Cristian; Estrada, Manuel; Chiong, Mario; Soto, Dagoberto; Parra, Valentina; Diaz-Araya, Guillermo; Jaimovich, Enrique; Lavandero, Sergio

    2006-03-01

    Androgens are associated with important effects on the heart, such as hypertrophy or apoptosis. These responses involve the intracellular androgen receptor. However, the mechanisms of how androgens activate several membrane signaling pathways are not fully elucidated. We have investigated the effect of testosterone on intracellular calcium in cultured rat cardiac myocytes. Using fluo3-AM and epifluorescence microscopy, we found that exposure to testosterone rapidly (1-7 min) led to an increase of intracellular Ca2+, an effect that persisted in the absence of external Ca2+. Immunocytochemical analysis showed that these effects occurred before translocation of the intracellular androgen receptor to the perinuclear zone. Pretreatment of the cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethylester and thapsigargin blocked this response, suggesting the involvement of internal Ca2+ stores. U-73122, an inhibitor of phospholipase C, and xestospongin C, an inhibitor of inositol 1,4,5-trisphosphate receptor, abolished the Ca2+ signal. The rise in intracellular Ca2+ was not inhibited by cyproterone, an antagonist of intracellular androgen receptor. Moreover, the cell impermeant testosterone-BSA complex also produced the Ca2+ signal, indicating its origin in the plasma membrane. This effect was observed in cultured neonatal and adult rat cardiac myocytes. Pertussis toxin and the adenoviral transduction of beta- adrenergic receptor kinase carboxy terminal peptide, a peptide inhibitor of betagamma-subunits of G protein, abolished the testosterone-induced Ca2+ release. In summary, this is the first study of rapid, nongenomic intracellular Ca2+ signaling of testosterone in cardiac myocytes. Using various inhibitors and testosterone-BSA complex, the mechanism for the rapid, testosterone-induced increase in intracellular Ca2+ is through activation of a plasma membrane receptor associated with a Pertussis toxin-sensitive G protein-phospholipase C

  8. 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

  9. 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.

  10. Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD.

    PubMed

    Somkuwar, S S; Kantak, K M; Bardo, M T; Dwoskin, L P

    2016-02-01

    Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5mg/kg) or water vehicle provided Monday-Friday from postnatal days 28-55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituted an adverse consequence associated with increased risk for cocaine abuse liability.

  11. Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

    PubMed Central

    Somkuwar, S.S.; Kantak, K.M.; Bardo, M.T.; Dwoskin, L.P.

    2016-01-01

    Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5 mg/kg) or water vehicle provided Monday-Friday from postnatal day 28–55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituting an adverse consequence associated with increased risk for cocaine abuse liability. PMID:26657171

  12. [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.

  13. 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.

  14. Using token reinforcement to increase walking for adults with intellectual disabilities.

    PubMed

    Krentz, Haley; Miltenberger, Raymond; Valbuena, Diego

    2016-12-01

    The purpose of this study was to evaluate the effectiveness of token reinforcement, using an ABAB reversal design, for increasing distance walked for adults with mild to moderate intellectual disabilities at an adult day-training center. Five participants earned tokens for walking 50-m laps and exchanged tokens for back-up reinforcers that had been identified through preference assessments. Token reinforcement resulted in a substantial increase from baseline in laps walked for 4 participants.

  15. Early maternal care predicts reliance on social learning about food in adult rats.

    PubMed

    Lindeyer, Charlotte M; Meaney, Michael J; Reader, Simon M

    2013-03-01

    Many vertebrates rely extensively on social information, but the value of information produced by other individuals will vary across contexts and habitats. Social learning may thus be optimized by the use of developmental or current cues to determine its likely value. Here, we show that a developmental cue, early maternal care, correlates with social learning propensities in adult rodents. The maternal behavior of rats Rattus norvegicus with their litters was scored over the first 6 days postpartum. Rat dams show consistent individual differences in the rate they lick and groom (LG) pups, allowing them to be categorized as high, low, or mid-LG mothers. The 100-day old male offspring of high and low-LG mothers were given the opportunity to learn food preferences for novel diets from conspecifics that had previously eaten these diets ("demonstrators"). Offspring of high-LG mothers socially learned food preferences, but offspring of low-LG mothers did not. We administered oxytocin to subjects to address the hypothesis that it would increase the propensity for social learning, but there were no detectable effects. Our data raise the possibility that social learning propensities may be both relatively stable throughout life and part of a suite of traits "adaptively programmed" by early developmental experiences.

  16. Beer improves copper metabolism and increases longevity in Cu-deficient rats

    SciTech Connect

    Moore, R.J.; Klevay, L.M. )

    1989-02-09

    Moderate consumption of alcoholic beverages decreases risk of death from ischemic heart disease (IHD). Evidence suggests that Cu-deficiency is important in the etiology and pathophysiology of IHD. The effect of beer (25 ng Cu/ml) drinking on the severity of Cu-deficiency was examined in weanling, male Sprague-Dawley rats fed a low Cu diet (0.84 {mu}g Cu/g). Beer drinking increased median longevity to 204 or 299 d from 62 or 42 d respectively in rats drinking water in two experiments (15 rats/group). In experiment 3, a single dose of {sup 67}Cu (3.3 {mu}Ci as chloride) was added to 1 g of feed and given to 12-h fasted rats 30 d after the start of the experiment. Whole body counting over 13 d showed apparent Cu absorption and t{sub {1/2}} (biological) were greater in Cu-deficient rats drinking beer than in similar rats drinking water. Plasma cholesterol was lower but hematocrit and liver Cu were higher in surviving rats drinking beer than in rats drinking water. Body weight was not affected by beer in any experiment. In experiment 4, a 4% aqueous ethanol solution had no effect on longevity of copper deficient rats. A non-alcohol component of beer alters Cu metabolism and mitigates the severity of nutritional Cu-deficiency in rats.

  17. Increased synthesis of glycosaminoglycans of the cornea during fasting and refeeding in rats

    SciTech Connect

    Mosier, M.A.; Jansons, R.A.; Mosier, H.D. Jr.

    1986-01-01

    The effect of a 48 hour fast on sulfate incorporation of corneal mucopolysaccharides was investigated in the rat. After fasting for 24 hours, experimental and control rats were injected intraperitoneally with /sup 35/S-sulfate. After fasting an additional 24 hours, the rats were sacrificed and incorporation of the label into the acid mucopolysaccharide fraction of the cornea was determined. Incorporation of the label into the acid mucopolysaccharide fraction was significantly increased in the fasted rat cornea. Increased synthesis of corneal sulfated mucopolysaccharides during fasting in the rat contrasts with the well known decreased synthesis in cartilage under the same conditions. These findings suggest that corneal acid mucopolysaccharide synthesis is selectively preserved and/or increased during fasting.

  18. Chronic exposure to low doses of lipopolysaccharide and high-fat feeding increases body mass without affecting glucose tolerance in female rats

    PubMed Central

    Dudele, Anete; Fischer, Christina W; Elfving, Betina; Wegener, Gregers; Wang, Tobias; Lund, Sten

    2015-01-01

    Obesity-related inflammation may have a causal role in the development of diabetes and insulin resistance, and studies using animal models of chronic experimental endotoxemia have shown the link. However, many studies use only males, and much less is known about the role of obesity-related inflammation in females. Therefore, we addressed how experimentally induced chronic inflammation affects body mass, energy intake, and glucose metabolism in female rats. Adult female Sprague Dawley rats were instrumented with slow release pellets that delivered a constant daily dose of 53 or 207 μg of lipopolysaccharide (LPS) per rat for 60 days. Control rats were instrumented with vehicle pellets. Due to inflammatory nature of high-fat diet (HFD) half of the rats received HFD (60% of calories from lard), while the other half remained on control diet to detect possible interactions between two modes of induced inflammation. Our results showed that chronic LPS administration increased female rat body mass and calorie intake in a dose-dependent manner, and that HFD further exacerbated these effects. Despite these effects, no effects of LPS and HFD were evident on female rat glucose metabolism. Only LPS elevated expression of inflammatory markers in the hypothalamus. To conclude, female rats respond to experimentally induced chronic inflammation by increasing body mass, but do not develop glucose intolerance in the given period of time. PMID:26537342

  19. ADOLESCENT INTERMITTENT ETHANOL EXPOSURE ENHANCES ETHANOL ACTIVATION OF THE NUCLEUS ACCUMBENS WHILE BLUNTING THE PREFRONTAL CORTEX RESPONSES IN ADULT RAT

    PubMed Central

    LIU, W.; CREWS, F. T.

    2016-01-01

    The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on–2 days off; P25–P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood. PMID:25727639

  20. Adolescent intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat.

    PubMed

    Liu, W; Crews, F T

    2015-05-07

    The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on-2 days off; P25-P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood.

  1. Increased phase synchronization of spontaneous calcium oscillations in epileptic human versus normal rat astrocyte cultures

    NASA Astrophysics Data System (ADS)

    Balázsi, Gábor; Cornell-Bell, Ann H.; Moss, Frank

    2003-06-01

    Stochastic synchronization analysis is applied to intracellular calcium oscillations in astrocyte cultures prepared from epileptic human temporal lobe. The same methods are applied to astrocyte cultures prepared from normal rat hippocampus. Our results indicate that phase-repulsive coupling in epileptic human astrocyte cultures is stronger, leading to an increased synchronization in epileptic human compared to normal rat astrocyte cultures.

  2. 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.

  3. Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

    PubMed Central

    Chan, Jackie K. W.; Fanucchi, Michelle V.; Anderson, Donald S.; Abid, Aamir D.; Wallis, Christopher D.; Dickinson, Dale A.; Kumfer, Benjamin M.; Kennedy, Ian M.; Wexler, Anthony S.; Van Winkle, Laura S.

    2011-01-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth. PMID:21914721

  4. Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs.

    PubMed

    Chan, Jackie K W; Fanucchi, Michelle V; Anderson, Donald S; Abid, Aamir D; Wallis, Christopher D; Dickinson, Dale A; Kumfer, Benjamin M; Kennedy, Ian M; Wexler, Anthony S; Van Winkle, Laura S

    2011-12-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth.

  5. Evidence for increased peroxidative activity in muscles from streptozotocin-diabetic rats

    SciTech Connect

    Lammi-Keefe, C.J.; Swan, P.B.; Hegarty, P.V.J.

    1984-05-01

    The ability of cardiac and skeletal muscles from diabetic rats to metabolize superoxide and hydrogen peroxide was determined by the activities of superoxide dismutase (SOD) and catalase, respectively. Male and female Sprague-Dawley rats, 43 days old, were made diabetic with a single intravenous injection of streptozotocin (70 mg/kg body weight). On the 80th day after injection the blood glucose concentration of these rats was increased fourfold, and the plasma insulin concentration was decreased four- to fivefold compared to controls. Body weights of male diabetic rats were 61% and those of female diabetic rats were 66% of their ad libitum-fed controls. The seven different skeletal muscles examined weighed less in the diabetic rats than in controls of the same age and body weight. Comparison to the body weight controls allowed the distinction of specific effects due to lack of insulin from effects due to retardation in muscle growth. Increased catalase activity in all muscles examined from diabetic rats (plantaris, gastrocnemius, and heart) suggested a response in catalase activity similar to that of starved rats. SOD activity was not altered in the diabetic rat skeletal muscles and erythrocytes, but was somewhat decreased in the heart.

  6. Effects of neonatal ganglioside GM1 administration on memory in adult and old rats.

    PubMed

    Silv, R H; Bergamo, M; Frussa-Filho, R

    2000-09-01

    Numerous investigations have been reporting the involvement of GM1 ganglioside in central nervous system development and memory formation. The effects of neonatal treatment with GMI ganglioside on the performance of adult rats in a plus-maze discriminative avoidance task and old rats in a step-down passive avoidance task were investigated. Rats were injected subcutaneously from day 3 to 15 after birth with 10 mg/kg GM1 or saline. GM1 treatment did not modify indicative landmarks of physical and motor development. Behavioural tasks were carried out when the animals were 4 (discriminative avoidance) or 24 (passive avoidance) months old. Discriminative avoidance conditioning was performed in a modified elevated plus-maze. During the training session, the animals received aversive stimulation (light and hot air blow) in one of the enclosed arms. Tests were performed 7, 14 and 21 days after conditioning (tests 1, 2 and 3), in the absence of the aversive stimulation. In all tests, GM1-treated animals spent less time in the aversive arm than in the non-aversive enclosed arm. Control animals, however, spent a shorter time in the aversive arm only in tests 1 and 2. Passive avoidance conditioning was performed in an acrylic box with a grid floor, that was partially covered by an inclined platform. Animals were placed on the platform and received a 0,5 mA foot shock when stepped down. A test was performed 48 hr later. Latency to step down presented by GM 1-treated animals was significantly higher in the test session, whereas no significant increase in latency to step down was found for control animals. The results suggest a possible action of GM1 on the maturation of the central nervous system that persists during adulthood and ageing.

  7. [The role of prenatal hyperandrogenism on lipid metabolism during adult life in a rat model].

    PubMed

    Heber, María F; Vélez, Leandro M; Ferreira, Silvana R; Amalfi, Sabrina; Motta, Alicia B

    2012-01-01

    Polycystic ovary syndrome (PCOS) is one of the commonest endocrine diseases that affect women in their reproductive ages; however, the etiology of the syndrome remains unknown. A hypothesis proposes that during gestation increased exposure of androgen would induce fetal programming that may increase the risk of PCOS development during the adult life. By means of a prenatally hyperandrogenized (HA) rat model we demonstrated the importance of determining the lipid profile at early ages. HA induced two different phenotypes: ovulatory and anovulatory PCOS. HA did not modify total cholesterol but decreased HDL cholesterol and increased both LDL and tryglicerides (TG) when compared with controls. Both, the ratio total cholesterol: HDL (marker of cardiovascular risk) and TG:HDL (marker of metabolic syndrome) were increased in the HA group with respect to controls. In addition, these abnormalities were stronger in the anovulatory than ovulatory phenotype. Our results point out the need to find early markers of PCOS in girls or adolescents with increased risk to develop PCOS (as in daughters of women with PCOS).

  8. 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.

  9. Eliminating Medicaid adult dental coverage in California led to increased dental emergency visits and associated costs.

    PubMed

    Singhal, Astha; Caplan, Daniel J; Jones, Michael P; Momany, Elizabeth T; Kuthy, Raymond A; Buresh, Christopher T; Isman, Robert; Damiano, Peter C

    2015-05-01

    Dental coverage for adults is an elective benefit under Medicaid. As a result of budget constraints, California Medicaid eliminated its comprehensive adult dental coverage in July 2009. We examined the impact of this policy change on emergency department (ED) visits by Medicaid-enrolled adults for dental problems in the period 2006-11. We found that the policy change led to a significant and immediate increase in dental ED use, amounting to more than 1,800 additional dental ED visits per year. Young adults, members of racial/ethnic minority groups, and urban residents were disproportionately affected by the policy change. Average yearly costs associated with dental ED visits increased by 68 percent. The California experience provides evidence that eliminating Medicaid adult dental benefits shifts dental care to costly EDs that do not provide definitive dental care. The population affected by the Medicaid adult dental coverage policy is increasing as many states expand their Medicaid programs under the ACA. Hence, such evidence is critical to inform decisions regarding adult dental coverage for existing Medicaid enrollees and expansion populations.

  10. Artificial reproduction of magnetic fields produced by a natural geomagnetic storm increases systolic blood pressure in rats

    NASA Astrophysics Data System (ADS)

    Martínez-Bretón, J. L.; Mendoza, B.; Miranda-Anaya, M.; Durán, P.; Flores-Chávez, P. L.

    2016-11-01

    The incidence of geomagnetic storms may be associated with changes in circulatory physiology. The way in which the natural variations of the geomagnetic field due to solar activity affects the blood pressure are poorly understood and require further study in controlled experimental designs in animal models. In the present study, we tested whether the systolic arterial pressure (AP) in adult rats is affected by simulated magnetic fields resembling the natural changes of a geomagnetic storm. We exposed adult rats to a linear magnetic profile that simulates the average changes associated to some well-known geomagnetic storm phases: the sudden commencement and principal phase. Magnetic stimulus was provided by a coil inductor and regulated by a microcontroller. The experiments were conducted in the electromagnetically isolated environment of a semi-anechoic chamber. After exposure, AP was determined with a non-invasive method through the pulse on the rat's tail. Animals were used as their own control. Our results indicate that there was no statistically significant effect in AP when the artificial profile was applied, neither in the sudden commencement nor in the principal phases. However, during the experimental period, a natural geomagnetic storm occurred, and we did observe statistically significant AP increase during the sudden commencement phase. Furthermore, when this storm phase was artificially replicated with a non-linear profile, we noticed a 7 to 9 % increase of the rats' AP in relation to a reference value. We suggested that the changes in the geomagnetic field associated with a geomagnetic storm in its first day could produce a measurable and reproducible physiological response in AP.

  11. Artificial reproduction of magnetic fields produced by a natural geomagnetic storm increases systolic blood pressure in rats.

    PubMed

    Martínez-Bretón, J L; Mendoza, B; Miranda-Anaya, M; Durán, P; Flores-Chávez, P L

    2016-11-01

    The incidence of geomagnetic storms may be associated with changes in circulatory physiology. The way in which the natural variations of the geomagnetic field due to solar activity affects the blood pressure are poorly understood and require further study in controlled experimental designs in animal models. In the present study, we tested whether the systolic arterial pressure (AP) in adult rats is affected by simulated magnetic fields resembling the natural changes of a geomagnetic storm. We exposed adult rats to a linear magnetic profile that simulates the average changes associated to some well-known geomagnetic storm phases: the sudden commencement and principal phase. Magnetic stimulus was provided by a coil inductor and regulated by a microcontroller. The experiments were conducted in the electromagnetically isolated environment of a semi-anechoic chamber. After exposure, AP was determined with a non-invasive method through the pulse on the rat's tail. Animals were used as their own control. Our results indicate that there was no statistically significant effect in AP when the artificial profile was applied, neither in the sudden commencement nor in the principal phases. However, during the experimental period, a natural geomagnetic storm occurred, and we did observe statistically significant AP increase during the sudden commencement phase. Furthermore, when this storm phase was artificially replicated with a non-linear profile, we noticed a 7 to 9 % increase of the rats' AP in relation to a reference value. We suggested that the changes in the geomagnetic field associated with a geomagnetic storm in its first day could produce a measurable and reproducible physiological response in AP.

  12. Microvillar size and espin expression in principal cells of the adult rat epididymis are regulated by androgens.

    PubMed

    Primiani, Nadia; Gregory, Mary; Dufresne, Julie; Smith, Charles E; Liu, Ye Lauren; Bartles, James R; Cyr, Daniel G; Hermo, Louis

    2007-01-01

    Principal cells of the epididymis are the most prominent cell type and are noted for an apical cell surface studded with microvilli. The latter contain channel proteins that condition the microenvironment of epididymal lumen and promote sperm maturation; however, the regulation of the structure and integrity of microvilli is not well known. Espins are a family of proteins implicated in microvillar growth. The objectives of this study were to assess the regulation of espin in epididymal principal cells both in vitro and in vivo. Treatment of immortalized rat caput epididymal (RCE) cells with increasing doses of a homogenized testicular extract revealed a dose-dependent increase in the size of microvilli. Reverse transcriptase-polymerase chain reaction (RT-PCR) of adult rat epididymal RNA using espin-specific primers indicated the presence of a band at about 290 base pairs (bp) in all regions. Western blot analysis using affinity-purified espin antibody confirmed the presence of an approximately 110-kDa band in the epididymis, corresponding to espin isoform 1. In adult rats, immunocytochemistry revealed espin expression over principal cells. In orchidectomized rats, espin expression was significantly reduced, whereas ligation of the efferent ducts resulted in a decrease of espin expression but not to the extent of orchidectomy. The fact that espin expression was restored to control levels in orchidectomized rats supplemented with high levels of testosterone indicated that its expression was dependent on androgens and not on other lumicrine factors derived from the testis. Taken together, these data indicate that espin is expressed in the epididymis and is regulated by androgens.

  13. Building a foundation for systems change: increasing access to physical activity programs for older adults.

    PubMed

    Lachenmayr, Sue; Mackenzie, Geraldine

    2004-10-01

    Although 25% of U.S. adults are physically inactive, this percentage increases dramatically for older adults. Organizational change theory guided a state health department in identifying system gaps and developing strategies to expand programming for seniors. A survey of provider agencies in New Jersey assessed (a) capacity for physical activity programs for older adults, (b) accessibility of programs, and (c) barriers to providing programs. One hundred sixty agencies provided physical activity programs to almost 184,000 individuals annually. Fewer than one half of the agencies provided exercise programs for people with disabilities, and only 44% provided in-home programs. Eighty-two percent of program providers wanted to expand programming but cited lack of trained instructors and peer leaders, inadequate facility space, insufficient funding, and limited transportation resources as barriers. Sustaining older adult behavior change requires infrastructure that will ensure access to diverse physical activities. This article provides strategies to expand access to physical activity programs for older adults.

  14. Increases in body mass of rats during spaceflight: models and measurements.

    PubMed

    Wade, C E; Ortiz, R M; Baer, L A

    2000-11-01

    To test the hypothesis that the body mass of rats is increased during spaceflight, we developed two models from the literature and obtained mass measurements during spaceflight. From studies of centrifugation (hypergravity), there is a reduction in body mass of rats dependent on the exposure gravity level. From data in 18 publications on rats subjected to hypergravity by centrifugation, we developed a model that predicted a 27% increase in body mass during the microgravity of spaceflight. Following spaceflight, with an increase in gravity on return to Earth, there is a reduction in body mass of rats for over 3 d. We related the reduction in body mass after spaceflight to the time after landing that mass measurements were made. From data in 23 publications on rats returning from spaceflight, we developed a model that predicted a 19% increase in body mass during spaceflight. Measurement of body mass of rats on days 6 and 10 of spaceflight found a 7 and 9% increase compared with ground control animals. The increase in body mass during spaceflight suggests that the rat may provide a viable model for metabolic studies in which changes during spaceflight may be predicted in part by ground-based hypergravity studies.

  15. Simultaneous subchronic exposure to selenium and diazinon as possible risk factor for osteoporosis in adult male rats

    PubMed Central

    2013-01-01

    Background Osteoporosis and its main health outcome, fragility fractures, are large and escalating health problems. Skeletal damage may be the critical result of low-level prolonged exposure to several xenobiotics in the general population, but the mechanisms of their adverse effects are not clearly understood. The current study was aimed to investigate the possible ability of simultaneous subchronic peroral administration of selenium (Se) and diazinon (DZN) to induce changes in bone of adult male rats. In our study, twenty 1-month-old male Wistar rats were randomly divided into two experimental groups. In the first group, young males were exposed to 5 mg Na2SeO3/L and 40 mg of DZN/L in drinking water, for 90 days. Ten 1-month-old males without Se and DZN intoxication served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy. Results The body weight, femoral length and cortical bone thickness were significantly decreased in rats simultaneously exposed to Se and DZN (P < 0.05). These rats also displayed different microstructure in the middle part of the compact bone where vascular canals expanded into central area of substantia compacta. The canals occurred only near endosteal surfaces in rats from the control group. Additionally, a smaller number of primary and secondary osteons, as well as a few resorption lacunae were observed near endosteal surfaces in rats simultaneously administered to Se and DZN. The resorption lacunae as typical structures of bone resorption manifestation are connected with an early stage of osteoporosis. Histomorphometric analysis revealed that area, perimeter, maximum and minimum diameters of primary osteons’ vascular canals were significantly increased (P < 0.05) in the Se-DZN-exposed rats. On the other hand, all measured variables of Haversian canals and secondary osteons were

  16. Maternal Omega-3 Supplementation Increases Fat Mass in Male and Female Rat Offspring

    PubMed Central

    Muhlhausler, Beverly Sara; Miljkovic, Dijana; Fong, Laura; Xian, Cory J.; Duthoit, Emmanuelle; Gibson, Robert A.

    2011-01-01

    Adipogenesis and lipogenesis are highly sensitive to the nutritional environment in utero and in early postnatal life. Omega-3 long chain polyunsaturated fatty acids (LCPUFA) inhibit adipogenesis and lipogenesis in adult rats, however it is not known whether supplementing the maternal diet with omega-3 LCPUFA results in reduced fat deposition in the offspring. Female Albino Wistar rats were fed either a standard chow (Control, n = 10) or chow designed to provide ∼15 mg/kg/day of omega-3 LCPUFA, chiefly as docosahexaenoic acid (DHA), throughout pregnancy and lactation (Omega-3, n = 11) and all pups were weaned onto a commercial rat chow. Blood and tissues were collected from pups at 3 and 6 weeks of age and weights of visceral and subcutaneous fat depots recorded. The expression of adipogenic and lipogenic genes in the subcutaneous and visceral fat depots were determined using quantitative real time reverse transcription-PCR. Birth weight and postnatal growth were not different between groups. At 6 weeks of age, total percentage body fat was significantly increased in both male (5.09 ± 0.32% vs. 4.56 ± 0.2%, P < 0.04) and female (5.15 ± 0.37% vs. 3.89 ± 0.36%, P < 0.04) offspring of omega-3 dams compared to controls. The omega-3 LCPUFA content of erythrocyte phospholipids (as a% of total fatty acids) was higher in omega-3 offspring (6.7 ± 0.2% vs. 5.6 ± 0.2%, P < 0.001). There was no effect of maternal omega-3 LCPUFA supplementation on the expression of adipogenic or lipogenic genes in the offspring in either the visceral or subcutaneous fat depots. We have therefore established that an omega-3 rich environment during pregnancy and lactation in a rodent model increases fat accumulation in both male and female offspring, particularly in subcutaneous depots, but that this effect is not mediated via upregulation adipogenic/lipogenic gene transcription. These data suggest that maternal n−3 LCPUFA

  17. Histological evidence of increased turnover in bone from spontaneously hypertensive rats.

    PubMed

    Barbagallo, M; Quaini, F; Baroni, M C; Barbagallo, C M; Boiardi, L; Passeri, G; Arlunno, B; Delsignore, R; Passeri, M

    1991-03-01

    24 weeks-old spontaneously hypertensive male rats and normotensive genetic controls were subjected to: histomorphometry of the proximal tibiae, assay of mineral density of the femurs by dual photon absorptiometry, and measurement of the calcium content of the femoral bone ash by atomic absorption spectophotometry. Compared with the controls, the hypertensive rats showed osteopenia and increased bone turnover; their osteoid volumes and the surface area of both osteoclasts and osteoblasts were all increased. The data suggest that, during aging, spontaneously hypertensive rats both lose bone mass more rapidly and also have an increased skeletal metabolic rate with respect to the controls.

  18. Adult rat bone marrow stromal cells express genes associated with dopamine neurons

    SciTech Connect

    Kramer, Brian C.; Woodbury, Dale . E-mail: WOODBURYDL@AOL.COM; Black, Ira B.

    2006-05-19

    An intensive search is underway to identify candidates to replace the cells that degenerate in Parkinson's disease (PD). To date, no suitable substitute has been found. We have recently found that adult rat bone marrow stromal cells (MSCs) can be induced to assume a neuronal phenotype in vitro. These findings may have particular relevance to the treatment of PD. We now report that adult MSCs express multiple dopaminergic genes, suggesting that they are potential candidates for cell therapy. Using RT-PCR, we have examined families of genes that are associated with the development and/or survival of dopaminergic neurons. MSCs transcribe a variety of dopaminergic genes including patched and smoothened (components of the Shh receptor), Gli-1 (downstream mediator of Shh), and Otx-1, a gene associated with formation of the mesencephalon during development. Furthermore, Shh treatment elicits a 1.5-fold increase in DNA synthesis in cultured MSCs, suggesting the presence of a functional Shh receptor complex. We have also found that MSCs transcribe and translate Nurr-1, a nuclear receptor essential for the development of dopamine neurons. In addition, MSCs express a variety of growth factor receptors including the glycosyl-phosphatidylinositol-anchored ligand-binding subunit of the GDNF receptor, GFR{alpha}1, as well as fibroblast growth factor receptors one and four. The expression of genes that are associated with the development and survival of dopamine neurons suggests a potential role for these cells in the treatment of Parkinson's disease.

  19. 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

  20. Increased susceptibility to amyloid-β toxicity in rat brain microvascular endothelial cells under hyperglycemic conditions.

    PubMed

    Carvalho, Cristina; Katz, Paige S; Dutta, Somhrita; Katakam, Prasad V G; Moreira, Paula I; Busija, David W

    2014-01-01

    We hypothesized that hyperglycemia-induced mitochondrial dysfunction and oxidative stress are closely associated with amyloid-β peptide (Aβ) toxicity in endothelial cells. Brain microvascular endothelial cells from rat (RBMEC) and mice (MBMEC) were isolated from adult Sprague-Dawley rats and homozygous db/db (Leprdb/Leprdb) and heterozygous (Dock7m/Leprdb) mice, and cultured under normo- and hyperglycemic conditions for 7 d followed by 24 h exposure to Aβ1-40. Some experiments were also performed with two mitochondrial superoxide (O2•-) scavengers, MitoTempo and Peg-SOD. Cell viability was measured by the Alamar blue assay and mitochondrial membrane potential (ΔΨm) by confocal microscopy. Mitochondrial O2•- and hydrogen peroxide (H2O2) production was assessed by fluorescence microscopy and H2O2 production was confirmed by microplate reader. Hyperglycemia or Aβ1-40 alone did not affect cell viability in RBMEC. However, the simultaneous presence of high glucose and Aβ1-40 reduced cell viability and ΔΨm, and enhanced mitochondrial O2•- and H2O2 production. MitoTempo and PEG-SOD prevented Aβ1-40 toxicity. Interestingly, MBMEC presented a similar pattern of alterations with db/db cultures presenting higher susceptibility to Aβ1-40. Overall, our results show that high glucose levels increase the susceptibility of brain microvascular endothelial cells to Aβ toxicity supporting the idea that hyperglycemia is a major risk factor for vascular injury associated with AD.

  1. Prolonged rest period enables the detection of micronucleated hepatocytes in the liver of young adult rats after a single dose of diethylnitrosamine or mitomycin C.

    PubMed

    Shimada, Keisuke; Yamamoto, Mika; Takashima, Miyuki; Seki, Jiro; Miyamae, Yoichi; Wakata, Akihiro

    2015-09-01

    A repeated-dose micronucleus assay utilizing young adult rat hepatocytes was recently developed to evaluate the genotoxicity. In this assay, accumulation of micronucleated hepatocytes (MNHEPs) induced by repeated dosing of genotoxic chemicals is considered to be a key factor in the detection of micronuclei induction. Then, we hypothesized that the period following chemical exposure enable the detection of MNHEP induction in young adult rats, namely that MNHEPs can be generated from chromosomally damaged cells and accumulate following initiation of chemical exposure until sampling. We therefore measured MNHEP induction at 2 or 4 weeks after a single oral administration of 12.5, 50, or 100mg/kg of diethylnitrosamine (DEN) or an intraperitoneal administration of 0.5, 1.0, or 2.0mg/kg of mitomycin C (MMC) to young adult rats. Results showed a statistically significant, dose-dependent increase in the numbers of MNHEPs in DEN- or MMC-treated rats, indicating that prolonged rest period following a single dose of a genotoxic chemical enables the detection of MNHEP induction in the liver of young adult rats. From these results, a single oral administration of 50mg/kg of DEN with a 2- or 4- week rest period can be used as a positive control in repeated-dose liver micronucleus assays. This procedure is superior in terms of labor saving and animal welfare to repeated dosing of DEN.

  2. Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain mitochondria from young-adult and old rats.

    PubMed

    Michelini, Luiz G B; Figueira, Tiago R; Siqueira-Santos, Edilene S; Castilho, Roger F

    2015-03-04

    Chronic and systemic treatment of rodents with rotenone, a classical inhibitor of mitochondrial respiratory complex I, results in neurochemical, behavioral, and neuropathological features of Parkinson's disease. The aim of the present study was to evaluate whether brain mitochondria from old rats (24 months old) would be more susceptible to rotenone-induced inhibition of oxygen consumption and increased generation of H2O2 than mitochondria from young-adult rats (3-4 months old). Isolated brain mitochondria were incubated in the presence of different rotenone concentrations (5, 10, and 100nM), and oxygen consumption and H2O2 production were measured during respiratory states 3 (ADP-stimulated respiration) and 4 (resting respiration). Respiratory state 3 and citrate synthase activity were significantly lower in mitochondria from old rats. Mitochondria from young-adult and old rats showed similar sensitivity to rotenone-induced inhibition of oxygen consumption. Similarly, H2O2 production rates by both types of mitochondria were dose-dependently stimulated to the same extent by increasing concentrations of rotenone. We conclude that rotenone exerts similar effects on oxygen consumption and H2O2 production by isolated brain mitochondria from young-adult and old rats. Therefore, aging does not increase the mitochondrial H2O2 generation in response to complex I inhibition.

  3. Both synaptic and intrinsic mechanisms underlie the different properties of population bursts in the hippocampal CA3 area of immature versus adult rats

    PubMed Central

    Shao, Li-Rong; Dudek, F Edward

    2009-01-01

    Pharmacological blockade of GABAA receptors on CA3 pyramidal cells in hippocampal slices from immature rats (i.e. second to third postnatal weeks), compared to CA3 slices from adult rats, is known to cause prolonged burst discharges (i.e. several seconds vs. tens of milliseconds). Synaptic and intrinsic mechanisms responsible for this developmental difference in burst duration were analysed in isolated minislices of the CA3 area. The frequency and amplitude of spontaneous EPSCs in CA3 pyramidal cells were greater in slices from immature than mature rats. In the presence of GABAA- and GABAB-receptor antagonists, the burst discharges of immature CA3 pyramidal cells were still prolonged in thinner slices (350 μm, vs. 450 μm in adults, to compensate for developmental differences in neuronal density) and in NMDA- and mGlu1-receptor antagonists. The AMPA receptor antagonist DNQX blocked the remaining burst discharges, suggesting that differences in recurrent excitatory circuits contributed to the prolonged bursts of immature CA3 pyramidal cells. In slices from immature versus adult rats, the CA3 recurrent synaptic responses showed potentiation to repetitive stimulation, suggestive of a lower transmitter release probability. The intrinsic firing ability was greater in CA3 pyramidal neurons from immature than adult rats, and the medium-duration afterhyperpolarization was smaller. These data suggest that, compared to adults, the CA3 area of immature rats contains a more robust recurrent excitatory synaptic network, greater intrinsic membrane excitability, and an increased capacity for sustained transmitter release, which together may account for the more prolonged network bursts in immature versus adult CA3. PMID:19884320

  4. 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

  5. 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…

  6. 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...

  7. 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...

  8. 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.

  9. Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

    PubMed

    Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

    2015-02-01

    Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

  10. Low and moderate doses of acute ethanol do not impair spatial cognition but facilitate accelerating rotarod performance in adolescent and adult rats.

    PubMed

    Novier, Adelle; Van Skike, Candice E; Chin, Vivien S; Diaz-Granados, Jaime L; Matthews, Douglas B

    2012-03-14

    Adolescents and adult rodents have differing sensitivities to the acute effects of ethanol on a variety of behavioral and electrophysiological measures. Often, these differences are revealed using high ethanol doses and consequently little is known about these age-related effects using lower ethanol doses. We sought to determine if low-dose ethanol produces differential effects on cognition and motor behavior in adolescent and adult rats. Adolescent (postnatal day PD 30-32) and adult (PD 70-72) male Sprague Dawley rats were trained on the standard version of the Morris Water Maze (MWM) for 5 days or received 5 training trials on an accelerating rotarod (ARR). Adolescents learned the location of the submerged platform in the MWM significantly slower than adults during training and, acute ethanol administration (0.5 g/kg, 0.75 g/kg, or 1.0 g/kg) 30 min before testing did not impair spatial memory in either age group. On the ARR test, adolescent rats spent significantly more time on the rotarod compared to adults and, alcohol exposure (1.0 g/kg) significantly increased ARR performance 30 min following administration. Our findings address the utility of investigating low and moderate doses of ethanol during different developmental stages in rats.

  11. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    PubMed

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  12. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  13. 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

  14. Adaptive changes in the motor cortex during and after longterm forelimb immobilization in adult rats

    PubMed Central

    Viaro, Riccardo; Budri, Mirco; Parmiani, Pierantonio; Franchi, Gianfranco

    2014-01-01

    Experimental and clinical studies have attempted to evaluate the changes in cortical activity seen after immobilization-induced longterm sensorimotor restriction, although results remain controversial. We used intracortical microstimulation (ICMS), which provides topographic movement representations of the motor areas in both hemispheres with optimal spatial characterization, combined with behavioural testing to unravel the effects of limb immobilization on movement representations in the rat primary motor cortex (M1). Unilateral forelimb immobilization in rats was achieved by casting the entire limb and leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and specific for the forelimb area, but were stronger in the contralateral-to-cast hemisphere. The threshold current required to evoke forelimb movement increased progressively over the period in cast, whereas the forelimb area size decreased and the non-excitable area size increased. Casting resulted in a redistribution of proximal/distal movement representations: proximal forelimb representation increased, whereas distal representation decreased in size. ICMS after cast removal showed a reversal of changes, which remained partial at 15 days. Local application of the GABAA-antagonist bicuculline revealed the impairment of cortical synaptic connectivity in the forelimb area during the period of cast and for up to 15 days after cast removal. Six days of rehabilitation using a rotarod performance protocol after cast removal did not advance map size normalization in the contralateral-to-cast M1 and enabled the cortical output towards the distal forelimb only in sites that had maintained their excitability. These results are relevant to our understanding of adult M1 plasticity during and after sensorimotor deprivation, and to new approaches to conditions that require longterm limb immobilization. PMID:24566543

  15. Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats.

    PubMed

    Torres, Sergio; Salgado-Ceballos, Hermelinda; Torres, José Luis; Orozco-Suarez, Sandra; Díaz-Ruíz, Araceli; Martínez, Angelina; Rivera-Cruz, Mario; Ríos, Camilo; Lara, Alicia; Collado, Carlos; Guizar-Sahagún, Gabriel

    2010-02-01

    Disability after traumatic spinal cord injury (TSCI) results from physical trauma and from "secondary mechanisms of injury" such as low metabolic energy levels, oxidative damage and lipid peroxidation. In order to prove if early metabolic reactivation is a better therapeutic option than antioxidant therapy in the acute phase of TSCI, spinal cord contusions were performed in adult rats using a well-characterized weight drop technique at thoracic 9 level. After TSCI, pyrophosphate of thiamine or non-degradable cocarboxylase (NDC) enzyme was used to maintain energy levels, antioxidants such as superoxide dismutase and catalase (ANT) were used to decrease oxidative damage and methylprednisolone (MP), which has both therapeutic properties, was used as a control. Rats were divided into one sham group and six with TSCI; one of them received no treatment, and the rest were treated with NDC, MP, NDC + MP, NDC + ANT or ANT. The ANT group decreased lactate and creatine phosphokinase levels and increased the amount of preserved tissue (morphometric analysis) as well as functional recovery (Basso, Beattie and Bresnahan or BBB motor scale). In contrast, NDC treatment increased lipid peroxidation, measured through thiobarbituric acid reactive substances (TBARS) levels, as well as spinal cord tissue destruction and functional deficit. Early metabolic reactivation after a TSCI may be deleterious, while natural early metabolic inhibition may not be a "secondary mechanism of injury" but a "secondary neuroprotective response". While increased antioxidant defence after a TSCI may currently be an ideal therapeutic strategy, the usefulness of metabolic reactivation should be tested in the sub-acute or chronic phases of TSCI and new strategies must continue to be tested for the early ones.

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

    PubMed